ANAS There “wad”, k: Presently but 3391 I113. t? m as a resc The re LL‘eNational 1 Sssearch at it “ito' Forty. it: 6‘23 moat} and maintainec ofaltitude f( “is made of ( (L) (2/ ABSTRACT QJAN AN ASSESSMENT OF HIGH ALTITUDE GRASSLANDS IN ECUADOR AS A RESOURCE FOR LIVESTOCK PRODUCTION BY Kim Alyn Wilson There are vast areas of high altitude grassland in Ecuador, known locally as paramo, that are unused presently but support the growth of forage, principally §Eipa_£ghu, throughout the year. This land could be used as a resource for livestock production. The research was conducted in cooperation with the National Institute of Agricultural and Livestock Research at its high altitude experiment station near Quito. Forty-eight Holstein males, weighing 120-438 kg and 6-28 months old, were divided into two equal groups and maintained in pastures at 12,000 and 13,800 feet of altitude for twelve months. During this time a study was made of changes in body weights, blood minerals, red blood cells, forage nutrient composition, forage minerals, forage digestibility and soil constituents. The effect on these measurements of feeding a balanced mineral mixture was an integral part of this study. The so. :agnesium, irc: ed zinc conce ieficiencies o The prl izcluded calcil :cgper. The fl zinc. The sodI | in: sodium, E level values. normal. The : 1“1331 values The In steadily dun were Slightly heman-Obit} CO EGCauSQ b100d ngObin in capacity of t ‘I .h e redLTCed P Alth classical Syn the animals ‘ let‘ St . aggerlng O t Kim Alyn Wilson The soil contained high quantities of calcium, magnesium, iron and organic matter. Potassium, copper and zinc concentrations, and pH were normal. There were deficiencies of phOSphorus and manganese in the soil. The principal mineral deficiencies in the forage included calcium, phOSphorus, magnesium, potassium and copper. The forage was high in manganese, cobalt and zinc. The sodium concentration was normal. The results of blood mineral analyses Showed that sodium, potassium and iron were above normal sea- level values. Serum magnesium concentrations were normal. The levels of calcium in the serum were below normal values measured at low altitude. The mean packed-cell volume of the blood increased steadily during the trial. Hemoglobin-bound iron values were slightly below those of sea level indicating that hemoglobin concentration did not increase with altitude. Because blood volume, red blood cell numbers and total hemoglobin increase with altitude, the oxygen-carrying capacity of the blood was sufficient to compensate for the reduced partial pressures of oxygen at high altitude. Although mineral imbalances were apparent, classical symptoms of specific mineral deficiencies in the animals were not observed. Skeletal degeneration, lethargy, rough hair coats, periodic lameness and staggering occurred prior to mineral supplementation. 3m though th zineral defici cfm'meral in: occurrence of :c: bly during abalanced mi: There the nineteen s l eilkeen mom} and nine deat‘: into a deep J l Brisk at high altitl SEW-Moms of tl no deaths Werl DeSpi high mortalit Body weight C traeeuminmal I was enhanCed balanCed to H ‘le Steers. It is f“men of : Kim Alyn Wilson Even though these symptoms often are indicative of mineral deficiencies, they are not fully diagnostic of mineral imbalances in livestock. The severity and occurrence of these symptoms, however, were reduced notably during a period of dietary supplementation using a balanced mineral mixture. There was a substantial mortality rate. Among the nineteen steers that died, fifteen were under eighteen months of age. Ten animals died from disease and nine deaths were due to falls over a high cliff or into a deep erosional chasm. Brisket disease, a common disorder in bovines at high altitude, was not a problem in this trial. Mild symptoms of the disease were detected occasionally but no deaths were attributable to the disorder. DeSpite the deficiencies of minerals and the high mortality rate, the survivors were able to gain body weight consuming only the native forage, water and trace-mineralized salt. The rate of body weight gain was enhanced appreciably when a mineral mixture, balanced to meet metabolic requirements, was fed to the steers. It is concluded from this study that the problems of maintaining livestock at high altitude are more a function of nutritional stress and less due to the stress of redut; sicrtage of que be alleviated J stress of reduced partial pressures of oxygen. The shortage of quality nutrients at high altitude must be alleviated in order to utilize the region efficiently. ANASE in Pa AN ASSESSMENT OF HIGH ALTITUDE GRASSLANDS IN ECUADOR AS A RESOURCE FOR LIVESTOCK PRODUCTION BY Kim Alyn Wilson A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Dairy Science 1975 My wif DEDICATED TO My wife, Dale, and my parents, whose faith has endured and enriched my life. ii Becaus this research} tributed t° it | The at ejar PrOfesso ccusel, encou of graduate St izzensely to t Sincer lizkel, Associ fessor of Geog lether of the enthusiasm has Career interes The at ACKNOWLEDGMENTS Because of the duration, location and scope of this research, the list is long of those who have con- tributed to its fruition. The author expresses sincere gratitude to his major professor, Dr. Robert M. Cook, for continual counsel, encouragement and interest during the course of graduate study. His inspiration contributed immensely to the personal development of the author. Sincerest appreciation is extended to Dr. C. W. Minkel, Associate Dean of The Graduate School and Pro- fessor of Geography, for his counsel and support as a member of the author's guidance committee. His enthusiasm has contributed greatly to the author's career interest in Latin American Studies. The author is grateful to Dr. Clinton E. Meadows, Professor, Department of Dairy Science and Dr. John M. Hunter, Director of the Latin American Studies Center and Professor of Economics, for their guidance and constructive criticism in the preparation of this dissertation. iii Thanks lain-nan of tha interest and c: afiy,and for Research Assis hs.Kay Butch Study. The in Satzel for co Apprec and Dr. Kirkpa izthe researc In Ecu °5 he. Fabian iehational 1 P“larch (INIA ieiication 0f aSS‘cred the Sq The in n: Mac tor Gene: meelated. me COntz-ibut DI. In . lonl Rihs, 3r, ,1 Ms, Ing c Thanks are extended to Dr. C. A. Lassiter, Chairman of the Department of Dairy Science, for his interest and counsel throughout the period of graduate study, and for financial support through a Graduate Research Assistantship. The author is grateful to Mrs. Kay Butcher for her assistance during graduate study. The invaluable assistance of Dr. Roger R. Neitzel for computer analysis is appreciated. Appreciation is extended to Dr. Irving R. Wyeth and Dr. Kirkpatrick Lawton for their long-term interest in the research program. In Ecuador, the personal interest and cooperation of Ing. Fabian Portilla R., former Director General of the National Institute of Agricultural and Livestock Research (INIAP) is deeply appreciated. The immense dedication of Ing. Portilla and the staff of INIAP assured the success of this research. The interest and support provided by the present Director General of INIAP, Dr. Enrique Ampuero P. is appreciated. The minds and hands of the following peOple have contributed immensely to the research project: Dr. Toni Rihs, Director of the Swiss Mission at INIAP, Dr. Gustavo Vera, Director of the Santa Catalina Experiment Station, Dr. Jorgé Roman, Ing. Luis Mano- salvas, Ing. Orlando Molina, Dr. Bolivar Espinoza, iv 3r. Jorgé Gonzc‘r Eisner, Sr. J'. Lag. Hilson Ca; Lain, Ing. Wal‘ Sincer. tales and Ing 65 their land The as $911119 and 1 W5 are ext interest and c The pr iiCrida MiSSio and assistance 3L Kamal Dow, DI. Roland Pou 7he aL ktereSt of t} Fellowships p; “diplomacy at . tribated grea la seriCa . Anal reciation 90: d3 .P 5a '(1 ”Tram Dr. Jorgé Gonzélez, Sr. Ricardo Rodriguez, Ing. Juan Sanchez, Sr. Juan Iturralde, Sr. Pedro Anacleto, Ing. Wilson Cajiao, Ing. Telmo Oleas, Ing. Vicente Ledn, Ing. Walter Estrella and Sra. Pilar de Vela. Sincere appreciation is extended to Ing. Carlos Ruales and Ing. Reuben Espinoza for the gracious donation of their land for the experiment. The assistance of Mrs. Connie Detering in sampling and laboratory analysis was of immense value. Thanks are extended also to Dr. David Nelson for his interest and counsel during the experiment. The professional staff of the University of Florida Mission to INIAP provided invaluable counsel and assistance. Deepest gratitude is extended to Dr. Kamal Dow, Mission Director, Dr. John Southcombe, Dr. Roland Poultney and Dr. Michael Schwartz. The author is grateful for the support and interest of the staff of the Latin American Teaching Fellowships Program of the Fletcher School for Law and Diplomacy at Tufts University. The fellowship con- tributed greatly to the entire experience in Latin America. And last, but in no way least, the deepest of appreciation goes to my wife, Dale, for her continual support and for her sacrifices throughout my educational program. In In. Lair .er I. Israoor II. REVIEW Chang EXpI Car r: Li; Pro Enz Min Vit Aci PhySi Bl He PT? Lur Ga: Kie En: TABLE OF CONTENTS Chapter Page I. INTRODUCTION . . . . . . . . . . . 1 II. REVIEW OF LITERATURE . . . . . . . . 15 Changes of Tissue Constituents During Exposure to Hypoxia . . . . . . . l7 Carbohydrates and Metabolic Inter- mediates . . . . . . . . . . 21 Lipids. . . . . . . . . . . . 24 Proteins and Nonprotein Nitrogen . . . 29 Enzyme Activity. . . . . . . . . 31 Minerals . . . . . . . . . . . 33 Vitamins . . . . . . . . . . . 36 Acid-base Balance . . . . . . . . 37 Physiological Changes During Hypoxia . . 38 Blood . . . . . . . . . . . . 39 Heart . . . . . . . . . . . . 50 Cardiac Hypertrophy. . . . . . . 50 Heart Rate. . . . . . . . . . 53 Cardiac Output . . . . . . . . 53 Lung . . . . . . . . . . . . 54 Gastrointestinal Tract and Accessory Organs . . . . . . . . . . . 55 Kidney. . . . . . . . . . . . 59 Endocrine Glands . . . . . . . . 60 Adrenal Gland. . . . . . . . . 61 Anterior Pituitary . . . . . . . 62 Gonads . . . . . . . . . . . 63 Uterus . . . . . . . . . . . 63 Thyroid Gland. . . . . . . . . 64 Pancreas . . . . . . . . . . 64 Heat Regulation and Hypoxia. . . . . 65 Central Nervous System . . . . . . 67 vi Capra: Nutri Dysf; Br: MO 1 AcclJ HY: Ac: Res Summ; ill. EXPERI! Bxpe; Expe: Del De Ma Chapter Nutrition During Exposure to Hypoxia Dysfunction During Hypoxia Brisket Disease Mountain Sickness. Acclimatization and Resistance Hypoxia . . Acclimatization Resistance to Hypoxia Summary. . . III. EXPERIMENTAL PROCEDURES Experimental Design. Experimental Site Description. Location . History . Topography Climate . Forages . Soils . . Development. Land Acquisition Access Road . Fencing . Water Supply. Corral. . Personnel. Management . Access Road . Fencing . Water Supply. Corral. . Personnel. Experimental Animals Genetic History Feeding Regime. vii Page 69 75 76 85 88 88 94 99 104 104 105 105 105 106 107 108 109 110 111 111 113 115 116 117 118 120 121 122 122 123 123 123 124 124 Crapter Gr He Chapter Pasture O O O O O O O O O O 0 Mineral Supplements . . . . . . . Water Supply . . . . . . . . . Grazing Management . . . . . . . . Movement of Animals . . . . . . . Pasture Burning . . . . . . . . Health Measures . . . . . . . . . Brisket Disease . . . . Pneumonia . . . . . . Parasites . . . Brucellosis and Tuberculosis . Hoof and Mouth Disease (Aphthous Fever). Hemorrhagic Septicemia . . . . . . Post-mortem Examination. . . . . Sample Collection . . . . . . . . . Body Weights . Blood . . Ages of Animals Identification Forages. . . Soil. . . . . Meteorological Data Altitude . . . Area of the Site. Analytical Methods. . . . . . . . . Macroelements and Microelements in BIOOd O O O O O O O O O O O 0 Preparation and Storage. . . . . . Atomic Absorption Spectrophotometry. . Calcium . . . . Magnesium . . Sodium . . . Potassium . . Serum Iron . . Hemoglobin-bound Iron Hematocrit. . . . . . . . . . . Forage Macroelements and Microelements . Proximate Analysis of Forage. . . . . viii Page 124 125 128 128 128 129 130 130 130 130 131 131 131 131 131 132 133 134 134 135 136 136 137 137 137 138 138 138 139 141 141 142 143 144 144 145 145 Chapter In Cel So: Ste IV. RESULTE EXpe 80' A!“ .- Chapter Page In Vitro Digestibility of Forage . . . 146 Cell-wall Constituents of Forage . . . 147 Soil Macroelements and Microelements. . 147 Statistical Analysis . . . . . . . 148 IV. RESULTS AND DISCUSSION. . . . . . . . 149 Experimental Animals. . . . . . . . 149 Body Weight Measurements. . . . . . 151 Mean Body Weights . . . . . . . 154 Summary of Mean Body Weight Data . . 163 Total and Average Daily Body Weight Gains. . . . . . . . . . . 163 Summary of Total and Average Daily Body Weight Gains. . . . . . . 166 Mean Body Weight and Survivability. . 167 Discussion of Body Weight Data . . . 168 Summary of Body Weight Measurements . 172 Age . . . . . . . . . . . . 174 Animal Mortality . . . . . . . . 176 Hematocrit . . . . . . . . . . 191 Blood Minerals . . . . . . . . . 197 Serum Calcium Concentration . . . . 199 Serum Magnesium Concentration . . . 204 Serum Sodium Concentration . . . . 206 Serum Potassium Concentration . . . 210 Serum Iron Concentration . . . . . 212 Concentration of Hemoglobin-bound Iron . . . . . . . . . . . 215 Summary of Blood Iron Content . . . 216 Concentrations of Other Microelements in Serum. . . . . . . . . . 218 Summary of Blood Analyses. . . . . 218 Forage Analysis. . . . . . . . . 223 Proximate Analysis and Total Digest- ible Nutrients of Paja g9 Paramo. . 224 Forage Digestibility . . . . . . 228 Cell-Wall Constituents and Ash, Silica and Nitrogen Content of Paja‘gg Paramo. . . . . . . . 228 Mineral Content of Paja d3 Paramo . . 231 Summary of Forage Analyses . . . . 233 ix tapter 50: Mi: MiH Obs V- CONCLUJ Conc: Reco: session . Chapter Page Soil Analyses . . . . . . . . . 234 Mineral Interrelationships. . . . . 237 Mineral Supplementation. . . . . . 240 Observation of the Steers . . . . . 243 V. CONCLUSION AND RECOMMENDATIONS. . . . . 247 Conclusion . . . . . . . . . . 247 Recommendations . . . . . . . . . 248 MPENDIX O O O O O O O O O O O O O O 2 54 LIST OF REFERENCES . . . . . . . . . . . 260 Idle 1. Blood Va 1L 1L RESidl Percente Value: it Hi: LEft an; Weigh' Level Body WELI SUDjEQ F8801: Changes Intake (ECuag compoSi1 in the LIST OF TABLES Table Page 1. Blood Values of Sea Level and High Altitude Residents . . . . . . . . . . . . 48 2. Percentage Change from Sea Level of Blood Values in Man and Three Animal Species at High Altitude O O O O O O O O O O 4 9 3. Left and Right Ventricular Ratios on a Weight Basis of Three Species at Sea Level and 13,100 Feet . . . . . . . . 51 4. Body Weight Gains and Feed Intakes of Rats Subjected to Two Altitudes and Three Feeding Schemes . . . . . . . . . . 72 5. Changes in Body Composition and Caloric Intake at High Altitude . . . . . . . 74 6. Mineral Composition of Trace Element Mixture (Ecuasal) . . . . . . . . . . . . 125 7. Composition of the Mineral Supplement Used in the Paramo. . . . . . . . . . . 127 8. The Number of Animals Included in Analytical Categories on Each Day of Blood-Sampling or Weighing . . . . . . . . . . . 152 9. The Dates and Days of the Experiment at Each Weighing of A11 Steers. . . . . . . . 153 10. The Dates and Number of Days in Each Weighing PeriOd O O O O O O O O O O O O O 15 3 11. Mean Body Weights of the Final Group of Steers on Each Weighing Date. . . . . . 155 12. Mean Body Weights of A11 Steers on Each Weighing Date. . . . . . . . . . . 156 xi w :32 .8 8. ll 21 H . Mean 80 ' Samar}, ' AVErage Mean Boi media‘ Total an per * Durint Total ai per A: Durin Mean Bo in thn Percei Steer Three Their Weigh (Lowe for E The Sin Body All 5 Date an Both “Gan In BOdY Steer ARima Categ Verso Serum o GrOup Table Page 13. Mean Body Weights of the Steers in the Inter- mediate Group on Each Weighing Date . . . 162 14. Total and Average Daily Body Weight Gains per Animal of the Final Group of Steers During Each Period. . . . . . . . . 164 15. Total and Average Daily Body Weight Gains per Animal of A11 Steers Remaining During Each Period. . . . . . . . . 164 16. Mean Body Weights at Each Weighing of Steers in the Final and Intermediate Groups as a Percentage of the Mean Body Weight of A11 Steers. . . . . . . . . . . . . 168 17. Mean Body Weights at Each Weighing of All Three Groups of Steers as a Percentage of Their Respective Initial Body Weights . . 171 18. Summary of Body Weights and Changes in Body Weight of the Final Group and All Steers (Lower and Upper Groups Combined). . . . 173 19. Average Age of Steers on Each Sampling Date for Each Treatment and Analytical Group. . 175 20. The Simple Correlations (r) of Age Versus Body Weight in the Final Group and in All Steers . . . . . . . . . . . 175 21. Date and Causes of Death of Steers at Both Altitudes . . . . . . . . . . 177 22. Mean Initial Body Weights and Average Daily Body Weight Change Prior to Death of Steers Not Surviving the Experiment . . . 189 23. Mean Hematocrit Values of Fifteen Control Animals and Steers in Three Analytical Categories . . . . . . . . . . . 192 24. The Simple Correlations (r) of Hematocrit Versus Age in the Final Group of Steers. . 194 25. Serum Calcium and Magnesium Concentrations by Analytical Category and Treatment Group 0 I O O O O O O O O O 0 O 200 xii Ede 2h 21 . Concentn ' In Vitr Wall I sen cI ' IndiVid Serum Si Analyi bound Categ Simple and B Group Summary of St Befor Proxina (DMD) of Yo Dry M Straw Mineral Mfitte Soil Mi PaStu Individ Of 57; Of St COACent and p the q ConCent and}: that; Table Page 26. Serum Sodium and Potassium Concentrations by Analytical Category and Treatment Group . . 207 27. Concentrations of Serum Iron and Hemoglobin- bound Iron for All Three Analytical Categories . . . . . . . . . . . 213 28. Simple Correlations (r) Between Serum Iron and Hemoglobin-bound Iron in the Final Group of Steers . . . . . . . . . . 218 29. Summary of Blood Analyses of the Final Group of Steers (Lower and Upper Groups Combined) Before and After Mineral Supplementation. . 219 30. Proximate Analysis, Dry Matter Digestibility (DMD) and Total Digestible Nutrients (TDN) of Young and Mature Paja de'Péramo on a Dry Matter Basis. . . . . . . . . . 225 31. In Vitro Organic Matter Digestibility, Cell- Wall Constituents, Silica, Ash and Nitro- gen Content of Paja dg'Paramo and Wheat Straw . . . . . . . . . . . . . 229 32. Mineral Content of Paja dg’Paramo on a Dry Matter Basis . . . . . . . . . . . 232 33. Soil Mineral Content and pH of the Paramo Pastures . . . . . . . . . . . . 235 34. Individual Body Weights of the Lower Group of Steers on Each Weighing Date. . . . . 254 35. Individual Body Weights of the Upper Group of Steers on Each Weighing Date. . . . . 255 36. Concentrations of Calcium, Magnesium, Sodium and Potassium in the Serum of Steers in the Lower Group on Each Sampling Date. . . 256 37. Concentrations of Calcium, Magnesium, Sodium and Potassium in the Serum of Steers in the Upper Group on Each Sampling Date. . . 257 xiii Tahoe 33. Consent: bound Volum. Lower 39. Concent bound Volur. Upper Table Page 38. Concentrations of Serum Iron and Hemoglobin- bound Iron and Percentage Packed-Cell VOlume in the Blood of Steers in the Lower Group on Each Sampling Date . . . . 258 39. Concentrations of Serum Iron and Hemoglobin- bound Iron and Percentage Packed-Cell Volume in the Blood of Steers in the Upper Group on Each Sampling Date . . . . 259 xiv Home Map of Mean BC Steer Mean B: Weigf Cumulat by Ca EXpe; Cumula* GIQQ‘ the ' Cumuia GIOU the LIST OF FIGURES Figure Page 1. Map of Ecuador . . . . . . . . . . 3 2. Mean Body Weights of the Final Group of Steers on Each Weighing Date. . . . . 158 3. Mean Body Weights of A11 Steers on Each Weighing Date. . . . . . . . . . 161 4. Cumulative Loss of Animals in Both Groups by Cause of Death and Day of the Experiment . . . . . . . . . . 181 5. Cumulative Loss of Animals in the Upper Group by Cause of Death and Day of the Experiment . . . . . . . . . 183 6. Cumulative Loss of Animals in the Lower Group by Cause of Death and Day of the Experiment . . . . . . . . . 185 XV CHAPTER I INTRODUCTION Yet despite all my preparations, when I went up the highest part of the range called Pariacaca, almost immediately I suffered anguish so severe that I had the idea of throwing myself from the cavalcade on to the ground . . . at the same time I retched and vomited so violently that I thought I was dying, because after throwing up food and phlegm, then bile and more bile, some yellow and some green, I finally vomited blood, on account of the violence which my stomach was suffering. If this had lasted I should certainly have perished but it did not continue for more than three to four hours until we had descended a considerable distance and arrived at a more suitable climate (147). This vivid account, written in 1589 by a Spanish missionary in Peru, describes accurately the extremes of discomfort that can be experienced at high altitude. Investigators of high altitude metabolism con- sider that a condition of stress exists for most organisms when they are subjected to either a true or simulated altitude of 5,000 feet or more. The stress is heightened as the altitude increases. The primary stress factor is a deficiency of oxygen, known as hypoxia. ieTserate 20: 10? level of is Suitable 4 receive adeq Periods. Mo CETEals' COL The of Ecuado r. 1'19 West COa ‘3 “I ee Climat is; . Mh lies I: Almost all previous research on high altitude phenomena has focused on the physiological aspects of abnormal performance due to hypoxia. There is, however, little information available on the nutritional aspects. The interdependence of nutrition and physiology in metabolic efficiency in environments below 5,000 feet of altitude has been well established. One purpose of this study was to investigate the role of nutrition in some of the various dysfunctions of high altitude metabolism. There are vast areas of open range land in the temperate zones of the Andes that are currently under a low level of production. The southern Andean countries of Peru and Chile have high altitude desert areas with small irrigated valleys. In Ecuador much of the land is suitable for crop and livestock production. There are ten major intermontane basins which generally receive adequate rainfall and suffer only moderate dry periods. Most of the cool-temperate zone crops such as cereals, corn, potatoes and onions, and pastures of grasses and legumes, are grown in the basins. The study was conducted in the Andes Mountains of Ecuador. The country is located on the equator on the west coast of South America. It is divided into three climatic zones (Figure 1): (1) the coastal plain, which lies between the Andes and the Pacific Ocean; ECUADOR — .._ Imam-bonnl boundary _ ._._ Prov: @ Notional capulal Provence capital RIIIFOId 5g u ‘M a. “’0 [Hm-mu". .‘P can. A g , l". Y: IMF luvs‘ 1’31"“ KEY 10 NAMES 0F PROVINCES l. ESMERALDAS 10. CHIMBORAZO 2. CARCHI ll. TUNGURAHUA 3. [MBABURA l2 1" A 4. MANABI l3, GUAYAS " 5.PICHINCHA MCANAR N ’7 .V 6. A 15. MORONASANTIAGO , t 'I. CUI‘OPAXI 16‘ AZUAY ;' 8 ms RICE 17, El. 0R0 ‘ ' A 9: BOLIVAR Is. A .v . 19. ZAMORA-(‘HINCHIPE . , . ‘ ',_v_ . .1. J \u‘ “ - A." '«m- a .~ , , Fig. 1. Map of Ecuador {2) the 233: to south in t J23, loca western part arinor agriC aggroximatel'; The populatic divided betwc country is irl Yet. it is g: Phl'siographic Gantry with agricultural There minced - TI (2) the sierra, formed by the Andes and extending north to south in the middle of the country; and (3) the oriente, located east of the sierra and forms the western part of the Amazon Basin. The Galapagos Islands, a minor agricultural zone, but a major tourist area, lie approximately 650 miles west of the Ecuadorian coast. The population exceeds six million inhabitants, evenly divided between the coastal and mountain areas. The country is in the beginning stages of industrialization. Yet, it is greatly dependent upon agriculture. The physiographic and climatic diversity provides the country with the potential to produce many kinds of agricultural products. There are shortages of milk and meat products in Ecuador and the other Andean countries. There are more than 1,000,000 dairy animals in the Ecuadorian sierra, including about 300,000 milking cows. The average daily milk production per cow is six pounds, compared with more than thirty pounds in the United States. Most of the milk is marketed in the major metropolitan areas with little reaching the rural Indian p0pulation. The average annual per capita consumption of milk is about thirty-five quarts. Part of the milk produced is marketed as cheese and some is fed to calves. Most of the meat production occurs on the coast and some is produced in the higher altitudes of the eastern forest region. The beef is apprc is of poor qu pricing incer not been deve Lives Primarily on on concentra: duction, Me: {98- dairy a Wine and P0: The rl 6 “he Ecuadori‘. region. The average annual per capita consumption of beef is approximately thirty-seven pounds. The meat is of poor quality because the grading standards and pricing incentives to produce high quality meat have not been developed. Livestock production in the sierra is based primarily on pastures, although there is some reliance on concentrates, especially for swine and poultry pro- duction. Meat production is based on the ruminant (e.g. dairy and beef cattle, sheep) and limited use of swine and poultry. The management practice of the dairy farmer in the Ecuadorian sierra can be discussed in general terms because of its simplicity. The system is based on pasture, but some grain feeding occurs. The primary energy source for milk production is grass pastures consisting of various ryegrasses, some orchard grass, timothy and bluegrasses. On many of the farms using improved management practices, some legumes are included in the pastures, with the clovers, alfalfa and vetches being the principal plants. A considerable amount of fertilizer, usually of high phosphorous content, is used in the sierra. The low productivity of dairy cattle in Ecuador is due to several factors. Almost all of the dairy cattle in the sierra are crosses of Holstein-Friesian and the nativ ate dairy cat, average age c six months, c Zzited States which reduces The animals 5 With an anI-é Peres with t: the United 8‘ low fertilit: Senen aVailal :etection an nation are a role in the and the native criollo cattle, A small percentage of the dairy cattle are purebred Holstein-Friesians. The average age of dairy heifers at first calving is thirty- six months, compared with twenty-four months in the United States. This is due, in part, to poor nutrition which reduces the growth rate and can affect fertility. The animals are small at the age of fifteen months, with an average body weight of 650 pounds, which com- pares with the goal of 750 pounds at fifteen months in the United States. Delayed breeding is due also to the low fertility of the bulls and the limited amount of semen available for artificial breeding. Poor estrus detection and incorrect timing of breeding or insemi- nation are also major factors. These conditions play a role in the extended calving interval, which is esti- mated at fifteen to eighteen months as compared with twelve to thirteen months in the United States. Inadequate reproductive efficiency, a low plane of nutrition and a prevalence of mastitis and disease cause a high culling rate. The rapid turnover of milking animals is about equal to the production of herd replacements. As a result, the national milking herd is increasing at a very slow rate, less than 1 percent annually. A common practice in the management of herd replacements is to nurse the calves on dams for several month adequate feed required to r I would be cons are weaned to weaning check need of the my herds 5; follow the c: infections, Milk PIOduct; fits of I good A ma;| rent involve:I about so perrl ““316 Cattle . 3r‘nagenent p; comtries. to Slaughter is Saved OCC‘ of the bette' several months. If this practice were followed by an adequate feeding regime after weaning, the time required to reach an acceptable breeding age or weight would be considerably reduced. However, the replacements are weaned to poor quality pasture and suffer a prolonged weaning check. The practice of grazing the young stock ahead of the dairy herd is employed occasionally, but many herds suffer from lungworm and the young stock follow the cows with a consequent contraction of adult infections. The emphasis of management practices is on milk production, with little attention paid to the bene- fits of good young stock management. A major decision to be made in dairy herd manage- ment involves the utilization of male animals, normally about 50 percent of the total calf crop. The use of male cattle is one focus of this study and is a major management problem in Ecuador and most other developing countries. In Ecuador the male animals are usually sent to slaughter within three days of birth. A bull calf is saved occasionally for use as a herd sire. On some of the better farms the bulls are castrated and milk-fed for veal. This is an expensive system and, although there is some demand for veal, the pricing incentives are not sufficient to encourage such utilization of the milk. One of the primary reasons given for not using the male animals for meat production is the lack of aniline nut for milk prOj long°tem mea The a reflection of are not utilil management 01 significantly the sierra is diction it 1: capacity of a hectare . If practices we could be inc per hectare. ‘I'ere only tc “testy to u available nutrients. The limited available nutrients for milk production apparently cannot be spared for long-term.meat production. The apparent lack of nutrients is mostly a reflection of poor management practices, since pastures are not utilized efficiently. Simple improvements in management of the available forage can accommodate a significantly larger cattle population. Land use in the sierra is not intensive. For areas in dairy pro- duction it is estimated that there is an animal carrying capacity of about one-half to one cow-equivalent per hectare. If proper pasture mixtures and management practices were adopted, the potential carrying capacity could be increased to almost four mature-equivalent head per hectare. Recent data indicate that if the farmers were only to adopt a recommended grazing interval of twenty to thirty days, instead of the present fifty to seventy days, milk production could easily be doubled and at least one-half of the present land in pastures could be put into other crOps or utilized by additional cattle (144, 145). This increase in milk production is based on a technological change. Unfortunately, an economic analysis was not included. The efficiency of agricultural production includes economic factors as well as technological factors. Livestock production in the Andes has depended on native herbage for centuries . have been bo' The l l I lational Ins of Ecuador ( pecuarias, I My under i which contri INIAP also r agencies, 5»; Foundation . The that of the the United S agricultural is“? 0f Ag: which is in Service aCti istrY- Iain centuries. In recent years improved varieties of forage have been both imported and developed locally. The study was conducted in cooperation with the National Institute of Agricultural and Livestock Research of Ecuador (Instituto Nacional de Investigaciones Agro- pecuarias, INIAP). This organization is a semiautonomous body under fiscal control of the Ministry of Agriculture, which contributes a large part of the annual budget. INIAP also receives grants and loans from outside lending agencies, such as the World Bank and the Rockefeller Foundation. The function of INIAP in Ecuador is similar to that of the Agricultural Experiment Station system of the United States. The major portion of Ecuadorian agricultural research is conducted by INIAP. The Min- istry of Agriculture also conducts research, much of which is in the field of animal health. Extension Service activities are likewise conducted by the Min- istry. INIAP consists of five major experiment stations, located so as to facilitate investigation of the technical and practical aspects of production which are reflected by the crops and livestock characteristic of the zone. There are four major stations on the coastal plain and one in the sierra, plus one smaller unit in the southern sierra now undergoing expansion. INIAZ fifteen year; severance of The organiza — 1. — _ - crass and, a ricians abro have returne cocplements Although “NC is highly Ca nifimnt agr the techniCa 10 INIAP has developed rapidly since its beginning fifteen years ago, due largely to the talents and per- severance of its director and staff during this period. The organization has been able to develop research pro- grams and, at the same time, send several of its tech- nicians abroad for graduate training. Many of these men have returned and are now conducting research which complements the national five-year plan for development. Although much more training is needed, the present staff is highly capable and creative, and dedicated to sig- nificant agricultural improvement. More than half of the technical personnel has the equivalent of bachelor's degrees. The training of the others is evenly divided between graduate degrees from other countries and no university education. INIAP initially had the objective of improving agricultural production in Ecuador, but much of the spe- cific research is also applicable to other Andean countries, especially in the mountainous areas common to these nations. A significant change in the economy of Ecuador occurred in mid-1972 when the country began exporting crude oil. A pipeline from the eastern forest region was constructed over the Andes to Esmeraldas, the major northern seaport. Between 200,000 and 250,000 barrels of crude oil are now exported daily. The government has begun cc :ation‘s de; I invorld oil I vith extra f Sinc available it sidera‘oly, lending ager. Elizdnation chemicals. alriculture ‘3 Percent c “Edit is a“. Till be di f :1 «L ‘ I ““9 inputs caPital Pres, supplies whe COIH ~C‘lad0r. ML of high Won Ks for C 11 has begun construction of a refinery to eliminate the nation's dependence on imported fuels. The rapid rise in world oil prices during 1973 provided the country with extra foreign exchange earnings. Since the middle of 1973 the amount of credit available for agricultural inputs has increased con- siderably. The capital has come from banks, outside lending agencies, the export of petroleum and the elimination of import duties on farm.machinery and chemicals. All banks are required to make loans to agriculture and small business amounting to at least 25 percent of their total loans. Although substantial credit is available, world supplies of fertilizer, farm machinery, grains and seeds are critical items in short supply. Major increases in agricultural productivity will be difficult to achieve until world supplies of these inputs become available. Previously, insufficient capital prevented large purchases of agricultural supplies when they were readily available and inexpensive. Corn and cereal grains are in short supply in Ecuador. Much of the grain has been exported because of high world prices, making it difficult to maintain stocks for domestic use. The government has developed marketing and pricing controls in an effort to increase grain reserves. These crops have longer growth cycles in the sierra than those in the major grain-producing areas of the country to II supplies. Fora for meat and shortage of t basins of t}: duction and cents. APP: in the highl of the bulls bECause therel available it PCtential Sc apparent lac Rune goats, 11am; Po "v- “admits su< 12 areas of the world. This makes it difficult for the country to recover rapidly from a deficit of grain supplies. Forages are the principal source of nutrients for meat and milk production in Ecuador, due to the shortage of grain. The pastures in the intermontane basins of the sierra are used mostly for milk pro- duction and for the growth of females as herd replace- ments. Approximately 80,000 dairy bull calves are born in the highlands of Ecuador each year. All but a few of the bulls are slaughtered within a few days of birth because they would compete for the limited nutrients available for milk production. These animals are a potential source of meat which is lost because of an apparent lack of alternatives. Ruminants (e.g. dairy and beef cattle, sheep, goats, llamas and alpacas) are efficient converters of poor quality, highly fibrous forage into high quality products such as meat and milk for human consumption. Most of the forage plants are unsuitable for consumption by humans or for economical production of monogastric livestock. There are approximately 2,400,000 acres of land above an altitude of 11,500 feet and extending to the rock faces of the mountain peaks above 14,000 feet. My a small Indians for he area is ecologically steep, undul resembles t‘; The cent grasses is high in f Between 11 ' S 13 Only a small part of this land is used, mainly by rural Indians for periodic grazing of sheep, goats and llamas. The area is called the param . It is geologically and ecologically similar to the Altiplano in Bolivia, but is steep, undulating and receives more rainfall. The area resembles the bunch-grass prairies of the United States. The vegetation in the péramo is more than 90 per- cent grasses. The dominant species is Stipa Ichu. It is high in fiber, low in protein and grows slowly. Between 11,500 and 12,000 feet of altitude some clover can be found. Lupines grow at all altitudes in the péram . The four factors above (the availability of animals, land and forage, combined with the metabolic characteristics of the ruminant) were basic to the justification of this study. The need to increase meat production for domestic consumption and the desire to investigate the potential of the péramo in meeting this need were expressed by government officials. Thus, the availability of resources, a recognized need and the potential for major agricultural impact form the basis of the investigation. An additional aspect was the author's desire to study the agriculture of a developing country, with a broader goal of gaining perspective on agriculture's role in the process of national deve10pment. Some features of conducted he to the need have been id 1. The Ecu: the shi: pron 2. The uti: 3' Am Con: The metabol. of high altl ductivity h { 14 Some of the economic, political and technological features of the environment in which this study was conducted have been discussed. Several factors related to the need for investigating this particular subject have been identified. The latter include: 1. The availability of essential resources in Ecuador, which if managed properly could provide the production of additional meat with a minimum shift of agricultural inputs away from existing production; 2. The suitability of the ruminant for maximum utilization of natural resources; 3. A need to increase meat production for domestic consumption; and 4. An availability of adequate technical support. The metabolic responses of man and animals to the stress of high altitude and the effect of this stress on pro- ductivity have yet to be considered. CHAPTER II REVIEW OF LITERATURE There is no doubt whatever that the cause of that strange disorder and alteration is the wind or atmosphere that prevails there, because the only treatment found . . . consists in covering the ears, nose and mouth as well as possible, and in clothing oneself well, especially over the abdomen. The air is so fine and penetrating that it enters the intestines. . . . I am convinced that the element of air . . . is so subtle and delicate that it is unsuitable for human reSpiration, which requires thicker and more tempered air. . . . It is extremely fine and delicate and its cold is not so much sensible as penetrative (147). During a crossing of the Peruvian Andes in 1589, Acosta not only described the event but he also ventured a theory about the factors that caused his extreme dis- comfort. His perception that some characteristic of the "air" was a factor has been shown to be correct but, this characteristic is now known to be the reduced partial pressure of air, especially of oxygen. He also perceived the phenomenon as a feature unique to the geographical location rather than one related to the high altitude of the area. Almost 300 years after Acosta wrote his account, controlled studies of high altitude phenomena and their 15 causes had t 1578 (19). existing at is the main éecrease in A pi etuo'y is re tally, redu 7.“. refore a hfloxia and linen consid ductivity 0 “5 Social animals: as the Stress dth ion or mark It In. Which haVe most POpul 5:000 feet Th iffeCts t} 0f the bot 16 causes had begun and were first summarized by Bert in 1878 (19). His review of the limited information existing at the time concluded that "oxygen deficiency is the main feature in all biological effects of a decrease in barometric pressure." A principal factor affecting the data of this study is reduced barometric pressure or, more specifi- cally, reduced partial pressure of oxygen (hypoxia). Therefore a review of the literature should emphasize hypoxia and its relation to other relevant factors. When considering any aspect of the study (e.g. the pro- ductivity of livestock, soil and plants, or economic and social ramifications), it is noteworthy that animals, as well as man, are continually exposed to the stress of hypoxia in the sierra of Ecuador. Hypoxia may pose constraints that greatly affect livestock pro- duction or the learning process and social behavior of man. .It may also alter some physical norms and concepts which have been established by studies conducted in the most populous stratum of the world, the area below 5,000 feet elevation. The exposure of man and animals to hypoxia affects their homeostasis. Homeostasis is a tendency of the body to maintain internal physiological and metabolic stability in response to conditions that disturb the normal functions of the body. The degree to which the iegends on t species and The l. The hypo 2. The to t duct 3. Some der: in: Hyp( Supply (269 or arbiem; With respec 5 '000 feet 17 to which the organism adjusts to the stress of hypoxia depends on the extent and duration of the stress, the species and nutritional status (269, 275). The literature reviewed covers three main areas: 1. The nutritional and physiological aspects of hypoxia; 2. The implications of metabolic changes related to the practical aspects of livestock pro— duction; and 3. Some pertinent, although limited, information derived from studies conducted at high altitude in South America. Changes of Tissue Constituents Burifig Exposure to Hypoxia Hypoxia is a condition of diminished oxygen supply (269). The term usually refers to the atmospheric or ambient conditions of low barometric partial pressure with respect to oxygen. Atmospheric conditions above 5,000 feet in elevation are considered hypoxic. Hypoxia also is used to define the existing condition at tissue and sub-cellular levels. Expressions synonymous to hypoxia include low (or reduced) oxygen tension, oxygen want, oxygen lack, oxygen deprivation and oxygen deficiency. The term "anoxia" is used interchangeably with ”hypoxia" by some authors, but it is unsuitable because it That, of co terrestrial The altitudes i the hypoxia pression ch these are fi‘ Meets Of the EXperim "sins Simul the baromet include a r barometri C The l to hYPOXia . air of the fact DIS, hy 0&6: than ( h ’h‘F’CXEmia) deficieth 18 because it literally means the absolute lack of oxygen. That, of course, is a state not encountered at any terrestrial altitudes under normal conditions (269). The principal stress of man and animals at high altitudes is decreased atmospheric oxygen pressure. The hypoxia of high altitude can be simulated in decom- pression chambers at any terrestrial altitude. However, these are most often used at low altitude to study the effects of hypoxia when it is inconvenient to conduct the experiments at high altitude locations. Most studies using simulated altitudes produce hypoxia by reducing the barometric pressure in the chamber. A few experiments include a reduction in the oxygen concentration while barometric pressure remains normal. The definition of the physiologists with respect to hypoxia is a deficiency of oxygen in the inspiratory air of the organism under study. Due to a variety of factors, hypoxia can cause an oxygen deficiency in tissues other than pulmonary alveoli. For example, anoxic hypoxia (hypoxemia) is a condition in which there is an oxygen deficiency in the arterial blood and the hemoglobin is not saturated with oxygen. Anemic hypoxia describes blood as having normal levels of oxygen with abnormally high amounts of circulating hemoglobin. In stagnant hypoxia there are normal amounts of oxygen and hemo- globin in the blood, but the oxygen is not given up to the tiss'l hypoxia the arable to me In a one can be 1 {269). The accidental‘i; 1119b. altit‘a inert gases SYStens of the most Se and Circula The Oriaa'lisms 1 altitude, 0 °f ”seen. to bECQme duration 0. certain Or that chl’On' fatiQUe (l “‘1 Partial pr baIOmetriC pressure a a he perCen 19 to the tissues in sufficient quantities. In histotoxic hypoxia the tissue cells are poisoned and therefore unable to make proper use of available oxygen. In addition to the above forms of hypoxia each one can be further delineated as either acute or chronic (269). The acute hypoxias occur rapidly and most often accidentally, such as losing pressure in aircraft at high altitude or inhaling oxygen-free, physiologically inert gases such as nitrogen or methane. Although all systems of the body can be affected by acute hypoxia, the most sensitive are the central nervous, pulmonary and circulatory systems. The chronic form of hypoxia is experienced by organisms living for moderate to long periods at high altitude, or by repeated exposure to subnormal supplies of oxygen. Depending upon the ability of the organism to become acclimatized to increased altitude, and the duration of the exposure, degenerative changes in certain organs may be produced. Barcroft has suggested that chronic hypoxia resembles mental and physical fatigue (14). Hypoxia has its direct effect through reduced partial pressure of oxygen, and not through lowered barometric pressure peg g3 (10, 269). The barometric pressure at sea level is 760 mm of mercury (Hg), and the percentage of oxygen is 20.96. Therefore the partial pres Ln conparim cehtage of J pressure of t‘at of sea The and animals 'v'an Liere a groduction ”ant; (3) t Phy’Sical cc The Which may i listed by u' Pheric preJ (l) temPEIJ Of Sunshine asst imPOIt pr655ure 01 It 20 partial pressure of oxygen at sea level is 159 mm Hg. In comparison, at an elevation of 14,000 feet the per- centage of oxygen remains at 20.96, but the partial pressure of oxygen is 94 mm Hg, which is only 60 percent that of sea level. The variables affecting the response of humans and animals to hypoxia were summarized individually by Van Liere and Stickney as: (1) the suddenness of the production of oxygen want; (2) the severity of oxygen want; (3) the duration of oxygen want; and (4) the physical condition of the body (269). The environmental variables at high altitude which may influence physiologic processes also were listed by Van Liere and Stickney: (l) lowered atmos- pheric pressure; (2) reduced partial pressure of oxygen; (3) temperature; (4) humidity; (5) increased intensity of sunshine; and (6) electrical conditions (269). The most important of these factors is the lowered partial pressure of oxygen, whereas the others may play subordi- nate roles. It is regretable that Van Liere and Stickney, as authors of an excellent textbook on hypoxia, ignored the possible role of nutrition or nutrient status in the above list of variables affecting physiologic pro- cesses. It is a contention of this dissertation that diet or nutrient quantity and quality can significantly roiifY the l conditions d Carbohydrate. HM variety 0f ‘ carb- hydrat‘ to carbon d via the pen associated metabolism are not aff Glu severe hypo lesser exte stated that altitudes 0 glucose is increase in El rise rapidl “ signifies Expcsures c °5 24.000 1 vation 0f k “Y the reg? b 21 modify the response of organisms when subjected to conditions of prolonged hypoxia. Qarbohydrates and Metabolic Intermediates Hypoxia alters carbohydrate metabolism in a variety of ways. The primary effects of hypoxia on carbohydrate metabolism are decreased glucose oxidation to carbon dioxide and a reduced utilization of glucose via the pentose shunt (25). These changes are directly associated with the metabolism of hexoses, since the metabolism of intermediates in the glycolytic pathway are not affected by hypoxia. Glucose tolerance is increased in conditions of severe hypoxia in animals (88, 152, 239, 274) and to a lesser extent in man (164, 225). Keyes and Kelley stated that their studies on dogs exposed to simulated altitudes of 18,000 and 24,000 feet indicate that glucose is converted to glycogen, which signifies an increase in glucose tolerance (152). Blood sugar levels in the dog, sheep and goat rise rapidly after exposure to high altitudes (269). A significant increase occurs in dogs even after exposures of only fifteen minutes to simulated altitudes of 24,000 feet and above (239). The most dramatic ele- vation of blood sugar is observed in the goat, followed by the response of the sheep (40, 240, 241). These changes rep? tan twice * say be more animals. A altitudes l: in nice (25 Thel glucose utiI the rat (25' | glucose oxi glucose Via the rat, 0., C Vali‘aes are metabolism ' s my be 0f 1 metabolism GIL € hYPOXia . 33y be boll: ms would 0 22 changes reported by Stickney and associates were more than twice those of the dog, suggesting that the ruminant may be more sensitive to hypoxia than monogastric animals. After three weeks' exposure to moderate altitudes blood glucose is normal or slightly reduced in mice (25). There are significant changes during hypoxia in glucose utilization by the liver, heart and muscle of the rat (26). The alterations are mainly a decrease in glucose oxidation to CO2 and reduced utilization of glucose via the pentose phOSphate pathway (25). In the rat, over one-third of the glucose was unaccounted for, suggesting that liver glycogen and blood sugar values are not adequate indices of carbohydrate metabolism (26). Glucose carbon can be incorporated into noncarbohydrate compounds such as triglycerides, phospholipids, amino acids and nucleic acids. These may be of importance in describing overall glucose metabolism at altitude. Glucose may protect or regulate surges of free fatty acid mobilization brought on by the stress of hypoxia. This protection occurs because acetyl CoA may be bound as forms of long-chain acyl CoA compounds. This would interfere with the oxidative decarboxylation of pyruvate to acetyl CoA. Gly ruscle of ar (26, 252). variable, dl :‘aress (269 the amount “RI paths. It the blood d Strated the elevated du after Sever lower than level, It 1&000 feel slightly ai t‘h‘o'lght thl protective “59 (70), Proe “er8 wile! Prod Uction setivitl’ as Unc MN 1 a o te l I 23 Glycogenesis is increased in the liver, heart and muscle of animals chronically exposed to high altitude (26, 252). The deposition of glycogen in the liver is variable, depending on the species and the hypoxic duress (269). The storage of tissue glycogen reduces the amount of glucose available for utilization by other major pathways. It is well known that lactic acid develops in the blood during exercise. Studies in the 1930's demon- strated that lactic acid levels in the blood are not elevated due to the stress of high altitude. In fact, after severe exercise at 12,000 feet, blood lactate was lower than that found after comparable exercise at sea level. It remained lower after the same exercise at 15,000 feet, and above 20,000 feet the lactate was only slightly above sea level values (28, 72, 77). It is thought that this behavior of lactic acid may be a protective mechanism during work or exercise at alti- tude (70). Hurtado stated that lactate and pyruvate production at altitude is unchanged from sea level values when the body is at rest (140). However, the production of both acids declines with strenuous activity at altitude while there is little change at sea level. Under normal oxygen conditions the changes in blood lactate correspond closely with changes in blood gyruvate (l the level c (135, 136). as: as blood pyruv clearly unc‘ | Al high altiti causes a r. aiecline a Tbilizatic Version of altitude. The of degs is when they ‘ ‘ ‘eet (202) transport or anOxia, absorb 9111 Li ids 24 pyruvate (135, 136). However, during anoxic hypoxia the level of lactate increases relative to pyruvate (135, 136). Since there is little change in lactate per se, as noted above, it is probable that a decline in blood pyruvate levels occurs. This phenomenon is not clearly understood (269). A main feature of carbohydrate metabolism at high altitude is an increase in glycogenesis, which causes a reduction of glycolysis. This, combined with a decline in acetyl CoA because of binding by fatty acid mobilization, may account for the decline of the con- version of pyruvate to lactate during exercise at high altitude. The absorption of glucose from the small intestine of dogs is slightly increased, but not significantly, when they are subjected to simulated altitudes of 27,000 feet (202). Although it has been shown in numerous studies that glucose absorption is a process of active transport under normal conditions, only complete hypoxia, or anoxia, will affect the ability of the intestine to absorb glucose under in vitro conditions (269). Lipids The few reported studies suggest that responses are variable with respect to the effect of hypoxia on blood lipids. Plasma phospholipids have been shown to l . mwm decrease in increased ( cholesterol llacLachlan strated the lipids with Hy; POSSible me Bass (51) . tnglyceric' 25 decrease in rabbits (244). In one study blood cholesterol increased (226). There are no reported cases of hyper- cholesterolemia in acclimatized Andean residents (139). MacLachlan conducted an extensive study which demon— strated that cats and dogs exhibit an increase in blood lipids with altitude, whereas the rabbit shows a decline (178). Hypoxia results in hypertriglyceridemia in rats. Possible mechanisms have been suggested by Chiodi and Bass (51). In hypoxia, the abnormally high release of triglycerides by the liver is faster than the adipose tissue can absorb them. Or, perhaps there is a decrease in the ability of adipose tissue to store those tri- glycerides entering the plasma at a normal rate. A third suggestion is that there may be an impairment of triglyceride synthesis by the adipose tissue. Chiodi and Bass conclude that low lipid utilization is a complex process with a low rate of resynthesis in adipose tissue, caused by a low glycerophosphate supply. Glycerophosphate is stimulated by carbohydrate intake and is needed by adipose cells for glyceride synthesis. This could explain the excess of plasma lipids and their consequent abnormal deposit in the liver. A study of serum lipid components in humans consisted of an adjustment period at sea level for fourteen days, followed by a period of nine days at ll,l00 feei altitude pl intake dur. fatty acid. iaz's; a Sta increase iv cant negat and calori fat'tY acid tissue the Palnitic a fatty acid authors CO Caloric re Changes of 14,100 fee altEratiOx CCSCCmita: A Janoski ( a dECrEaS C Lat 1055 . “A h by“ sumpti c aEEt “18;: «ass (49) 26 14,100 feet (278). Compared with sea level the high altitude period resulted in a decrease of caloric intake during the nine days; an increase in serum-free fatty acids the first day, which remained for the nine days; a steady weight loss; a significant and continued increase in triglycerides after day six, and a signifi- cant negative correlation between serum-free fatty acids and caloric intake. As a result of mobilization of fatty acids from the triglyceride pool, in the adipose tissue the percentage of linoleic acid decreased while palmitic and oleic acids increased in both the free fatty acid fraction and the triclyceride fraction. The authors concluded that there is a direct effect of caloric restriction on serum free fatty acids. These changes of serum lipids in humans abruptly exposed to 14,100 feet altitude probably reflect neuroendocrine alterations in the mobilization of stored lipids with concomitant decreases in body fat. According to Surks et al. (245) and Whitten and Janoski (278) high altitude exposure is accompanied by a decrease in body weight which is primarily due to fat loss. However, studies with rats show that oxygen consumption increases at altitudes of 14,100 or 20,000 feet when expressed per unit of lean body mass or cell mass (49). The change occurs primarily in the lean ass and is the fat-ire Ra: from 8,000 abso. tion from 24,00: reduction . 14,100 fee‘ fat absor; . or both (a, distinguis (:1 high altitl right Vent there We“ phosphOIi; mcafdial 1885 Of tr refleCtiOn Tv rabbits li renal tllbu “Set Of ‘h shat there lc~ :S were is in 27 mass and is attributable, in part, to alterations in the fat-free composition of the body. Rats exposed to simulated altitudes ranging from 8,000 to 18,000 feet showed no differences in fat absorption over sea level exposure (181). However, from 24,000 to 28,000 feet there was a significant reduction in fat absorption. Also, between 5,280 and 14,100 feet there appears to be either a decrease in fat absorption, or a decline in apparent fat digestion, or both (49). This latter study was not designed to distinguish between the two effects. Gloster et al., using pair-fed rats exposed to high altitude, reported there was a decrease in total right ventricular lipid and triglyceride (98). However, there were no differences in pulmonary lipids or cardiac phospholipids. There was a significant decline in myocardial cholesterol and cholesterol ester, regard- less of treatment in older rats, which was seen as a reflection of diet. The data of Rasmussen clearly show that in rabbits lipids are accumulated in the myocardium and renal tubular cells within forty-eight hours after the onset of starvation (214). MacLachlan demonstrated that there was no effect on blood lipids when cats and dogs were starved in high altitude conditions and blood lipids in rabbits declined (178). Hi: with a pro: lipids: to pig ; phos; ethanolarni: 509. guine. Choline (In guinea pig and choles neutral liv l 60;, and n. Values in fatty acid at altitud Gr effect of betabolism . l Londlitions acids for 28 High altitude conditions have been associated with a pronounced increase in the following cardiac lipids: total myocardial lipids (rabbit, dog, guinea pig); phOSphatidic acid (rabbit, dog); phosphatidyl ethanolamine (rabbit, dog); sphingomyelin (rabbit, dog, guinea pig); lysolecithin (rabbit); phosphatidyl choline (rabbit, dog); phosphatidyl inositol (rabbit, guinea pig); phosphatidyl serine (rabbit, guinea pig) and cholesterol (rabbit, dog, guinea pig) (99). Total neutral lipids were higher in the rabbit, lower in the dog, and not significantly different from sea level values in the guinea pig. The percentage of saturated fatty acids in phospholipids was significantly lower at altitude for all three species, as was the triglyceride content. Grice and coworkers recently demonstrated the effect of excess cobalt on myocardial function and lipid metabolism (115). It is well known that under normal conditions rat myocardium oxidizes long chain fatty acids for its energy requirements in preference to pyruvate or glucose, and in the absence of these long chain fatty acids pyruvate is greatly preferred. How- ever, excess cobalt administrated intraperitoneally to rats significantly decreased the ability of the myo- cardium to oxidize octanoate and pyruvate (73, 263). This resulted in degenerative heart lesions associated with incre: decreased 1 difficult * to an anim. chloride. combined or Md system animal. D 29 with increased myocardial lipid and ground substance and decreased myofibrils. Based on this information it is difficult to understand the protective effect provided to an animal under hypoxia when treated with cobalt chloride. It appears that the condition of hypoxia combined with cobalt therapy would increase cardiac and systemic lipids beyond a level beneficial to the animal. Diet quantity and quality should play a major role in these phenomena. But, little emphasis has been placed to date on the role of nutrition and its interaction with lipid metabolism during hypoxia. The main feature of lipid metabolism during exposure to hypoxia is an increase in blood lipids caused by neuroendocrine changes. The mobilization of fatty acids causes a loss in body weight and an increase in the deposit of fat in the liver. There is a change in the fatty acid composition of lipid components and an increase in phospholipids. The normal contribution of energy by carbohydrates is reduced and compensated by increased lipid metabolism. Proteins and Nonprotein Nitrogen There is a dramatic increase in serum protein levels when the net change of altitude is 8,000 feet or more (269). High altitude exposure is often associated with a negative nitrogen balance in man and rats, due :ainly to a in the tur: exposed to there was 1 Klein and hypoxia re :a-tabolisr; levels of lith terre Th decreased than 23,03. Cyanide pc lilIllted fC (91) and h Ia. H It is then, 105‘ 18. HQ nltrOlBen e he. . nonpro te i r (32 l. Th1 in .. sluCOne T .n natins 30 mainly to a decrease in serum amino acids and an increase in the turnover of serum albumin (154). When rats were exposed to an altitude of 14,110 feet for thirty days there was no effect on tissue storage of amino acids. Klain and Hannon determined that an acute exposure to hypoxia results in a transitory increase in protein catabolism (154). Early studies indicated that the levels of nonprotein nitrogen in the blood do not change with terrestrial altitude (269). The absorption of glycine is significantly decreased by hypoxia equivalent to altitudes greater than 23,000 feet (202). Only in complete hypoxia or in cyanide poisoning (histotoxic hypoxia) is tran5port limited for the L-forms of methionine (280), alanine (91) and histidine and phenylalanine (3). It has been demonstrated that anoxic hypoxia causes a decrease in the excretion of ammonia (65, 118). It is thought that the decrease is a response to alka- losis. However, Brunquist observed an increase of total nitrogen excretion (urea, ammonia, creatine) in severe hypoxia, which was similar to the increase in urinary nonprotein nitrogen observed in fasting rats in hypoxia (32). This phenomenon may be a reflection of an increase in gluconeogenesis from protein during hypoxia (269). In natives of sea level compared with natives of high altitude , auscle tis Th are observ Enzyme Act Ti. hypoxia. cytochrome oxidase 5;. results of that rats signifiCa: “Sinine g 00?. aftEr H; the Effec increase _' be °Per I at. with the a Rs in asthma: (whole hotl high altis tranShYdrl latter ml 31 altitude, there were no significant differences in muscle tissue (216). The most significant changes in protein metabolism are observed as alterations of enzymes. Enzyme Activity The activity of several enzymes increases in hypoxia. Among these are transhydrogenase, NADPH- cytochrome C reductase and the mitochondrial NADH- oxidase system as reported by Hurtado (140, 141). The results of a study of rats by Klain and Hannon indicate that rats exposed to an altitude of 14,110 feet had significantly higher hepatic arginase and hepatic arginine synthetase activities after two days, but not after thirty days (154). Hurtado summarized the limited information on the effects of hypoxia on enzyme activity as an apparent increase in oxygen utilization (140). This appears to be Operative along the pathways linked preferentially with the production of high-energy phosphate bonds. Reynafarje studied muscle myoglobin and enzymes in natives of sea level and at an altitude of 14,400 feet (216). Myoglobin was significantly greater at high altitude than at sea level. Muscle NADH-oxidase (whole homogenate), NADPH-cytochrome C reductase and transhydrogenase (24,000 xg fractions only for the latter two enzymes) were all significantly higher in activity a significan isocitric activities capacity 0 0f altitud As exposed to “tame t {272). As slutamic a and Plasma 8ffects wd exposure, variation earlier, 5 activity, gll'COgen ] canny rec H1 shOh’ed all tranSMin‘ a 510 a ops“! The 32 activity at altitude than at sea level. There were no significant changes in NADH-cytochrome C reductase, isocitric dehydrogenase or lactic dehydrogenase activities. The author concluded that the respiratory capacity of muscle is apparently higher in the native of altitude compared with that of the sea-level native. Aspirin (acetylsalicylic acid) feeding to rats exposed to hypobaria has been shown significantly to increase the glucose-6-phosphatase activity in the liver (272). Aspirin also increased liver activities of glutamic oxalacetic- and glutamic pyruvate-transaminases and plasma levels of glutamic acid, but none of these effects were significantly affected by high altitude exposure. Altitude exposure did shift the diurnal variation of blood glucose (glucose was higher, earlier, after feeding), lowered the liver phosphorylase activity, and was associated with lower peak liver glycogen levels. According to the authors, the most important practical aspect of the study with regard to the animal was the lowered hematocrit, which signifi- cantly reduced blood viscosity. Humans treated with metelone acetate and vitamins showed an increase in the activities of glutamic pyruvic transaminase, lactic dehydrogenase and aldolase when blood-sampled at altitudes up to 20,000 feet (5). There was no change in creatine phosphokinase activity due to alt drugs can to become T1" not been t, is derived The macro- f°r a Wide EXlSt 0n 1 L; on blOOd 5 Suggest t‘: althOUgh : increases mil affl the abSOl’y in the dov lvypox'la iv radical, ‘ difficted 1 Us lei/e18 in exposure With asp}? l l ~ I 010 .llifiCE1 33 due to altitude. The implication of the study is that drugs can improve, though variably, the ability of man to become acclimatized to high altitude conditions. Minerals The effect of hypoxia on mineral metabolism has not been thoroughly studied. Most existing knowledge is derived from research conducted at low altitude. The macro-elements and micro-elements are necessary for a wide variety of biochemical reactions. Few data exist on the requirements for minerals at high altitude. Little is known about the effects of hypoxia on blood sodium and chloride levels. Available data suggest that there is no significant change (269), although it has been indicated that blood chlorine increases at altitude, while sodium levels are mini- mally affected (140). Mild degrees of hypoxia reduce the absorption of isotonic sodium chloride solutions in the dog (267). The absorption of sodium chloride in hypoxia is not affected by the presence of sulfate radical, the absorption of which, itself, is not affected by even severe degrees of hypoxia (270). Under controlled laboratory conditions, potassium levels in the blood appear to decrease rapidly after exposure to anoxic hypoxia (84). This is in contrast with asphyxia, in which blood potassium increases significantly due to its mobilization primarily by the liver secreted b Hurtado s .. at altitu A humans we: were main intake (1 and an in Changes (4. serum, 5 “Ptake is 34 the liver in response to epinephrine which is rapidly secreted by the adrenal glands (43, 69, 282). However, Hurtado suggested that the change in potassium is minimal at altitude (140). After a two-week sea level control period, humans were subjected to nine days at 14,100 feet and were maintained on a constant sodium and potassium intake (146). A decrease of urinary potassium excretion and an increase in serum potassium were observed. No changes were noted for sodium concentration in urine or serum. Since Luft et al. showed that maximum oxygen uptake is directly related to muscle potassium content (173), the retention of potassium during hypoxia may be a protective mechanism. The levels of calcium in the blood of humans appear to be similar regardless of altitude (140). According to Hurtado in 1964, no research at high altitude on the levels of magnesium and sulfate radical have been reported (140). An increase of phosphorus in the blood occurs during hypoxia. The change primarily is in the level of 2,3-diphosphogly- cerate, the major red blood cell phosphate. This chemical regulates the affinity of hemoglobin for oxygen and its availability to tissues (165, 204). The level of 2,3-diphosphoglycerate in humans returned to normal after one week of exposure to an altitude of 14,300 feet. deficiencg the kidne; range fro... rats consul that high on magnes; I: iron defic of 4,000 l [168), A1 Sllbjects 5 hemc‘atocril and total Volume an; h1°00 eel; are 9180 C in iron‘do be aggrdVg hi'POxia. 35 Under normal barometric conditions iron deficiency increases the accumulation of magnesium in the kidney, liver and testes of rats (44). The increases range from 2.0 to 2.5 times the control levels when the rats consume a normal intake of iron. It is expected that high altitude would aggravate the effect of iron on magnesium metabolism. In an Ecuadorian study, fifteen patients with iron deficiency anemia were transported from an altitude of 4,000 feet to Quito, at an altitude of 9,300 feet (168). After exposure to the new altitude, all of the subjects showed pronounced increases in hemoglobin, hematocrit, red cell number and volume, blood volume and total plasma iron. Decreases were noted in plasma volume and iron disappearance time. No change in red blood cell turnover time was observed. These changes are also observed upon ascent to even greater altitudes. An iron-deficiency anemia existing at low altitude can be aggravated when the anemic patient is exposed to hypoxia. Central American natives have major deficiencies of folic acid and vitamin 812 (86). These hemopoeitic factors were probably involved in the etiology of the anemias found in Central America and were due to con- Sumption of diets in which 75 percent of the calories were from carbohydrates and very few were from animal products . be exagge. Vitamins C 60mg of * Significa. When they 15,700 fe greater, 36 products. It is expected that the vitamin status would be exaggerated at altitude (86). Vitamins Chicks and hens raised on a diet enriched with 60 mg of vitamin E per pound of feed demonstrated a significant increase in resistance to disease (248). When they were exposed to a simulated altitude of 15,700 feet the immune response was significantly greater, suggesting a synergistic effect of hypoxia and vitamin E. The authors indicated that perhaps the vitamin E was acting as an antioxidant and, combined with hypoxia, created greater reducing conditions in the electron transport chain for cellular development. Resistance to disease in hypoxic, normoxic and hyperoxic conditions is highly variable, with or without vitamin therapy. Schmidt suggests that more work should be done and, for the moment, only one generalization can be made: modified environments may affect host suscep- tibility to infectious disease (227). Ascorbic acid levels in the blood are lower in hypoxia in guinea pigs and hamsters, and scurvy develops more readily (29, 31, 116). The ascorbate requirement for man is not increased at altitude (269). The requirement of man for thiamine is not changed during prolonged exposure to hypoxia (109, 269). Sreiq and in tissue? :oenzynne 1 is assent; pyruvate i would inc: blood. 'r; studies c: a decline Hr 0f acidos blood aci C“rently conciition I alkaline T altitude as follow decreaSeS turn Prod tensign ( in. 37 Greig and Govier stated that extensive dephOSphorylation in tissues occurs in hypoxia (114) and may include the coenzyme thiamine pyrophosphate (109). The coenzyme is essential for the oxidative decarboxylation of pyruvate to acetyl CoA and C02. Its dephosphorylation would increase thiamine and pyruvate levels in the blood. This is not consistent with the results of studies on carbohydrate metabolism, which showed that a decline in blood pyruvate occurs in hypoxia. Acid-base Balance Hypoxia was originally thought to be a problem of acidosis, because of the net production of various blood acids and a decline in alkaline reserves. It is currently considered that alkalosis is the prevailing condition in hypoxia, despite an apparent decline in alkaline reserves (269). The mechanism of the production of alkalosis at altitude has been summarized by Van Liere and Stickney as follows: hypoxia causes hyperventilation, which decreases alveolar carbon dioxide tension, which in turn produces a lowering of the arterial carbon dioxide tension (269). In an attempt to maintain an acid-base balance in the body, the kidneys secrete more base, especially more plasma bicarbonate. This continues until the reduction in plasma bicarbonate is proportional to the re. effect is data indi to about either 1; severe cc 1 0f high a (loss of alkalosis arrival 5 acclimat] is in fig: Stickney e"Plain t altituae an inCl‘er; remins mechaniS: the lunggl is direca Cil’culatC 38 to the reduction in carbon dioxide tension. The net effect is a slight increase in blood pH. Most recent data indicate that alkalosis occurs at altitudes up to about 12,000 feet. Above this altitude there is either little change or a return to normal. Unless severe conditions exist, alkalosis is produced. Von Muralt reported that a well-established fact of high altitude physiology is the development of acapnia (loss of C02) in the blood, which leads to respiratory alkalosis (274). Acapnia occurs within one day after arrival at high altitude and rapidly disappears as acclimatization proceeds. This mechanism of alkalosis is in agreement with the summary by Van Liere and Stickney (269). However, the mechanism does not fully explain the respiratory alkalosis resulting from high altitude exposure, because after returning to sea level an increased sensitivity of the receptors for CO2 remains for weeks and, in some cases, even months (274). Physiological Changes During Hypoxia The stress of hypoxia affects several homeostatic mechanisms. The organs most sensitive to hypoxia are the lungs, heart and kidney. Much of the sensitivity is directly related to the hematological changes in the circulatory system. The endocrine and central nervous systems also are disturbed by hypoxia. Blood the blood in the m; erythrocy 269). TL". - _—_ —_—_ — rarily tc barametri denonstra in inSpixi Pressure Oxygen wt. was aSSO} Their St! the resu‘} | Under Cor {Slated 1: 39 Blood One of the most dramatic and rapid changes in the blood in hypoxia is polycythemia, i.e. an increase in the number of circulating red blood cells, both for erythrocytes and reticulocytes (10, 37, 75, 82, 141, 269). This polycythemia has been shown to be due pri- marily to oxygen insufficiency, rather than to diminished barametric pressure pg£_§g (62, 140). Dallwig et al. demonstrated as early as 1915 that reduced total oxygen in inspired air, whether due to lowered barometric pressure or to a reduction of the concentration of oxygen while maintaining sea-level barometric pressure, was associated with a significant polycythemia (62). Their study was performed using several species, and the results have been confirmed by a myriad of authors. Under conditions of chronic hypoxia it is known that the polycythemia is not as dramatic and is closely related to other changes in blood components. Carbon monoxide inspired in sufficient quantity to saturate the hemoglobin up to 33 percent can produce a marked polycythemia (198). However, carbon dioxide has a lowered partial pressure at high altitude which minimizes its erythropoietic action. Some suggested causes of hypoxic polycythemia may be summarized as follows: (1) an unequal distri- bution of red blood cells throughout the body; (2) a lengtheni increased high alti latent st at high a Poietic a three the role in } that p013 In some a blood Stc Studies Q results he the Splee circulati and racir Significa relEaSed. ashOrt E I il I l l | | l 40 lengthening of the life span of erythrocytes; (3) increased irradiation by the more powerful sunlight at high altitudes; (4) the presence of an auxiliary or latent store of red blood cells; (5) a hemoconcentration at high altitudes; and (6) an acceleration of hemato- poietic activity of red bone marrow (269). The first three theories have been shown to have little or no role in hypoxic polycythemia. It is generally believed that polycythemia is due largely to hemoconcentration. In some animals there may be a mobilization of cells from blood stores in the body (8, 110, 142). Although many studies of erythrocyte mobilization have provided results which are inconclusive, some data show that the spleen contracts and releases red cells into the circulation. Collins and Farrell state that the horse and racing greyhound are unique in that they have a significant splenic reserve of erythrocytes which is released, on demand, into the general circulation within a short period (54). The sixth theory mentioned above by Van Liere and Stickney (269) is valid because it is known that there exists a circulating erythropoietic stimulating factor in animals which have been exposed to low oxygen tension. Also, a humoral factor, called hemopoietine, is involved in the polycythemic response to hypoxia (105, 110). b—L reSponse (192). S with lO-ZI of body a occurred. p ”l to bloOc HCuld pl< to maint r the Era/t; 41 The sequence of events in the erythropoietic response of rats has been described by Miller et al. (192). Six hours after subcutaneous injection of rats with 10-25 micromoles of cobalt chloride per 100 grams of body weight, a dose-related respiratory alkalosis occurred, associated with an increase in the affinity of hemoglobin for oxygen, followed by an increase in the production of erythropoietin. In nephrectomized rats, opposite effects occurred after cobalt chloride administration. The kidney appears to be the primary site of erythropoietin production. It is stimulated by a decrease in tissue oxygenation, as a result of the alkalosis which increases the affinity of hemoglobin for oxygen. This decreases the amount of oxygen available to the tissues, resulting in histotoxic hypoxia (80, 192). The greatest polycythemic change appears during a change in elevation from sea level to 6,000 feet. The rate of change is less above 6,000 feet, although the number of cells continues to increase. This diminution in the rate of polycythemia prevents the blood from becoming excessively viscous, which would place too much strain on the heart while trying to maintain blood circulation. In studies on horses transported to 7,000 feet altitude it was shown that the erythropoietic response was incomplete even after an exposr which do horses 9: puscular tration. most dra: altitude 4 hours af tine reg Variable aOaths, time and that the exhibits some WEE natiVe t long Per This is COnteht macmCi/t OCCurs I cells (1 lng a 42 an exposure of seven weeks (54). Compared with cattle, which do not show as dramatic an erythropoietic response, horses greatly increase their hematocrit, mean cor- puscular volume and mean corpuscular hemoglobin concen- tration. The increase in cell number and hemoglobin is most dramatic during the first three days at high altitude. Although the polycythemia reverses within a few hours after return to sea level or low altitude, the time required to obtain a normal blood picture is highly variable. The adaptation period can be as long as six months, depending on individual differences and the time and extent of exposure. Hurtado et al. reported that the blood of persons native to high altitude exhibits the same morphological characteristics after some weeks at low altitude as those found in persons native to low altitude (198). The size of red blood cells can increase during long periods at high altitudes (74, 139, 142, 171). This is associated with an increase in hemoglobin content of the red blood cells (142). Although macrocytosis occurs in most cases, at times anisocytosis occurs, which is an inequality in the sizes of the cells (171). Changes in blood volume are highly variable during acute hypoxia and no consistent change has been determine an increa largely a mass (lOJ in blood observati Bolivia concentr; at 14,89I (273), changes ( rather t; "‘15 thou Studied of age w from M ihCreaSe being tr l.340 fe as did t Of the b to 7.73 ”'03 De the cont lids mobi 43 determined. However, during chronic hypoxia there is an increase in blood volume in both man and animals, largely as a result of the expansion of the red cell mass (10, 142, 217). The first evidence of an increase in blood cell volume was reported as early as 1891 in observations at sea level and in the Andes of Peru and Bolivia (273). Viault determined that the red cell 6 concentration at sea level was 5 x 10 cells/mm3, and at 14,890 feet it had risen to 7.5-8.0 x 106 cells/mm3 (273). This was also the first evidence that blood changes occur in a very short time after exposure, rather than during generations of acclimatization as was thought until that time. The effect of hypoxia on blood volume has been studied in goats (20). Three female goats at six months of age were exposed for eleven weeks to pasturing from 6,100 to 8,230 feet elevation. Their body weight increased continually, except for a depression after being transferred to the high area from an altitude of 1,340 feet. Total blood volume increased significantly as did the body content of the blood, from 6.86 percent of the body weight at the control altitude (1,340 feet) to 7.73 percent at high altitude, and returned to normal (7.03 percent) after an eight-week recovery period at the control level. The reserve blood volume apparently was mobilized during the initial five weeks at altitude, and litti nts to increase percent reserves by adren altitude Plasma v decreasE i3 Often hl'POXia occurs d mechanis fol1nd th to the a c0‘n‘ditic in rats below 4’ Liere de kidney. subjectE feet (15 but the W5; her 1C 44 and little storage was accomplished. Metabolic adjust- ments to hypoxia in the remaining weeks permitted an increase in the storage of blood reserves, up to 12.2 percent of the total blood volume. Most of the blood reserves are maintained in the spleen and are released by adrenaline-like compounds. Grawitz, in 1895, was the first to report that altitude exposure was associated with a reduction in plasma volume (111). The plasma volume generally decreases during acute anoxic hypoxia, but the response is often inconsistent under conditions of chronic hypoxia (82, 269). It has been clearly shown that body water loss occurs during anoxic hypoxia, which is the primary mechanism in hemoconcentration (8, 142). Stickney found that body weight loss in rats was proportional to the altitude, up to 28,000 feet, under simulated conditions (238). The thresholds for body weight loss in rats via feces lie between 4,000 and 8,000 feet; below 4,000 feet for urinary loss. Lawless and Van Liere determined the water content of the cerebrum, kidney, liver, muscles, skin and adrenal gland in rats subjected to simulated altitudes from 8,000 to 28,000 feet (161). Above 8,000 feet all animals lost weight, but the organ weights changed little except for some water loss from muscle and skin at 18,000 feet. It was concl prinaril; the resuj its home: the extrl to lose ' an altit during t the body the tota recovers In a 32~ altitude "35 resel decompar Water incrGas reSPlra altitud Bent high (H liters the int Magma during 45 was concluded that the body weight loss was related primarily to hemoconcentration. The interpretation of the results was “that the body, in order to maintain its homeostatic state, allowed the blood, and perhaps the extracellular spaces rather than the tissue cells, to lose water" (161). In rats exposed continuously to an altitude of 15,000 feet, body water loss was greatest during the first week. During this time 20 percent of the body water was lost, accounting for 94 percent of the total body weight loss (209). During acute hypoxia, body water declines but recovers to normal levels after acclimatization (207). In a 32-day trial with sheep conducted at a simulated altitude of approximately 18,000 feet, water balance was restored by the end of the test period. This was accompanied by a marked increase in extracellular water, little change in plasma volume, a definite increase in basal metabolic rate and a decrease in the respiratory quotient. The sheep adapted well to high altitude in 4 1/2 weeks and stabilized in the environ- ment. In a study with humans, an acute exposure to high altitude conditions resulted in a shift of three liters of body water from the extracellular space to the intracellular space with a concomitant decrease in plasma volume (121). This relative change was maintained during the fourteen days of the study. In comparison with seve duration a return there is Per unit l9l3 it hemOglob decrease and disc levels i hemoglc‘: (l, 10, Clearly i“CreaSe 10, 35, tration, 5100;} i: The her: the SPEC consenSL “miller (I bhrden C and the the hen. 15,700 :i 46 with several other studies, it would appear that the duration of this trial was not long enough to observe a return to normal of the variables studied. It has been demonstrated conclusively that there is an increase in the total amount of hemoglobin per unit of body weight during hypoxia. As early as 1913 it was established that in humans of both sexes hemoglobin rises about 10 percent for every 100 mm Hg. decrease in barometric pressure (85). Both the chronic and discontinuous forms of hypoxia increase hemoglobin levels in many species of animals. Total circulating hemoglobin increases more than does the concentration (1, 10, 35, 53, 92, 187, 235). This phenomenon is not clearly understood. The number of red blood cells increases in equal prOportion with the hemoglobin (l, 10, 35, 53, 235). As would be expected in hemoconcen- tration, both the viscosity and specific gravity of the blood increases at high altitude (l, 10, 35, 53, 235). The normal value in man is 1.055, while at 14,100 feet the specific gravity increased to 1.073. The general consensus of investigators is that the increase in number of red cells does not place an extraordinary burden on the circulatory system. In a study of chicks and the effect of supplemental vitamin E in hypoxia, the hematocrit at 4,900 feet was 34 percent and at 15,700 feet was 45 percent. The hemoglobin was 40 mg/ 10 suppleme had no e either a signific which we There a; cation c ability Stress ( combinat nifiCant hEmOglO‘i altitllde therapy nicotin" when} to the C treatmer ferEnt l K I 3S‘dal’ e ‘ L0 altit 47 40 mg/100ml and 50mg/100ml, respectively, when no supplemental vitamin E was given. Additional vitamin E had no effect on the hematocrit and hemoglobin at either altitude. However, the vitamin did have a significant effect on the production of immunocytes, which were greatly increased at altitude (248). Hemoglobin varies with species (27, 55, 75). There appears to be a relationship between the classifi- cation of hemoglobin types (e.g. A, B, C) and the ability of the animal to adjust to or withstand hypoxic stress (27). The anabolic hormone, metelone acetate, in combination with a B-vitamin complex produced a sig- nificant increase in erythrocytes, hematocrit, and hemoglobin when humans were subjected to a range of altitudes from sea level to 20,000 feet (5). Vitamin therapy with vitamins 31' B2, 36' 312’ pantothenic acid, nicotinic acid and vitamin C was associated with insig- nificant changes in hematological values as compared to the combination with metelone acetate, but both treatments at all altitudes were significantly dif- ferent from sea level hematological values during a 35-day experiment (5). Hematological changes are significantly related to altitude and reflect the process of adaptation. Reynafar; of sea 11 Blood % 8100 K Henatocr HenOglob Ml‘Oglobi (mg/gm Eelmglo‘o (Rig/gm \ increaSe concentr animal SI Tal’Jle 2 I as an if ChdHQES the Prip 48 Reynafarje reported the hematological values in natives of sea level and altitude shown in Table l (216). Table 1 Blood Values of Sea Level and High Altitude Residents Sea Level High Altitude BIOOd component Native Native (14,100 ft.) Hematocrit (a) 43.30 i 2.50a 52.40 : 2.55b Hemoglobin (gm/100 cc) 14.41 a 0.88 17.03 : 0.89b Myoglobin (mg/gm fresh tissue) 6.07 i 0.70 7.03 t 0.73c Hemoglobin (mg/gm fresh tissue) 5.93 t 2.44 9.58 i 2.94c aMean 1 standard deviation bp < 0.001 CP < 0.02 Burton and co-workers have summarized the increases over sea-level values in hematocrit, hemoglobin concentration and erythrocyte count of man and three animal species adapted to high altitude, as shown in Table 2 (36). The results in Table 2 were interpreted as an indication that "the greatest and most consistent changes (in hypoxia) involve the oxygen-carrying capacity of the blood" (36). The authors also concluded that the primary erythrocytic response of the chicken is apparently a "net increase in total circulating red blood cells." Percen Eenatocr Benoglot Erythroc \ blOOd cg With the cell cor Concurrv the blo< actual l: dition' and is cont(int PEnSate Conttint 49 Table 2 Percentage Change from Sea Level of Blood Values in Man and Three Animal Species at High Altitude Blood Component Man Rat Mouse Chicken --------- percentage increase—-------- Hematocrit 28 15 20 27 Hemoglobin 29 20 26 36 Erythrocyte count 26 25 22 33 The oxygen capacity, or the amount of oxygen the blood can actually contain if exposed to air, increases with the number of red blood cells. The increase in red cell count with altitude is an excellent measure of the concurrent increase in the oxygen-combining capacity of the blood (50, 70, 133). The oxygen content, or the amount of oxygen actually present in the blood under a particular con- dition, is best measured with respect to oxygen capacity and is expressed as "percent saturation." The oxygen content declines with increased altitude, which is com- pensated for by an even greater increase in hemoglobin content of the blood (10, 87, 269). The coagulation time of blood decreases with increased altitude, but the response is highly variable among species (269). Hemolysis occurs only when the oxygen tension is greatly reduced, generally at altitudes above 18,000 fee considerat: Lei circulatini tine immed ever, the cells, 1.8 variation the polymc large 1m; nan (139). It Upon EXpog ‘0 Provide lncrec‘asinl H T, 1°“ Parti the {10w maintain liSm. 50 18,000 feet (269). Red blood cell fragility is of minor consideration below this altitude. Leucocytosis, or an increase in the number of circulating white blood cells, occurs for only a short time immediately after exposure to high altitude. How- ever, the proportion of the various types of white blood cells, i.e. the differential count, shows considerable variation both among and within species. For example, the polymorphonuclear cells may decline in favor of large lymphocytes in animals, but not necessarily in man (139). It is evident that the body reacts immediately upon exposure to hypoxia, a response which attempts to provide more oxygen to the tissues by rapidly increasing the oxygen binding and transport systems. Heart The heart is a primary organ that responds to low partial pressures of oxygen. Its role is to increase the flow of blood to the tissues to an extent that will maintain a supply of oxygen adequate for tissue metabo- lism. Cardiac Hypertrophy: The occurrence of cardiac hypertrophy is a significant physiological response to hypoxia (269). It is observed in species resident but not native to high altitude for periods of six months or longer, 269). In h only if the (252, 269). two ways: ”Eight, or left ventrj have summer rcib'oits an: Stated thal increase it, for the le high altit Left andE Th" \ S \ Gui Ra DOg \ arl b “O at right in Cattle. h; 51 or longer, and in natives of high altitude (141, 252, 269). In hypoxia, cardiac hypertrOphy is significant only if the degree and/or the duration is considerable (252, 269). Cardiomegaly is most often measured in two ways: (1) as the ratio of heart weight to body weight, or (2) as the ratio between the weights of the left ventricle and right ventricle. Gloster et al. have summarized the latter measurement in guinea pigs, rabbits and dogs as shown in Table 3 (99). The authors stated that these data support the observation that the increase in right ventricular size is greater than that for the left ventricle when these Species are exposed to high altitude. Table 3 Left and Right Ventricular Ratios on a Weight Basis of Three Species at Sea Level and 13,100 Feet Species Sea Level 13,100 Feet Guinea Pigs 3.2 2.6a Rabbits 3.5 1.9a Dogs 3.3 2.2b ap < 0.01 bp < 0.05 Badeer stated in a review of cardiac hypertrophy that right ventricular hypertrophy has been demonstrated in cattle, rabbits, lambs, pigs, guinea pigs, mice, horses, 11a high altitL' ration (10) to cardiac pressure. shows a rag EXposure tc In high altit showed that with an inc “eight (98, intake is 1 Whether die hypertmph1 Va: weight Verl “I the 0,. reported t the Sea le hlpertrOph SIX weeks 52 horses, llamas, chickens, pigeons and dogs native to high altitudes or after varying periods of acclimati- zation (10). Dogs native to sea level are resistant to cardiac hypertroPhy when subjected to low barometric pressure. The neonatal chick native to high altitude shows a rapid increase in right ventricular size upon exposure to hypoxia (37). In a study of rats at sea level, or pair-fed to high altitude intake or at high altitude, Gloster et al. showed that only high altitude conditions were associated with an increase in right ventricular size and lung weight (98). Cardiac hypertrophy occurs when dietary intake is reduced in hypoxia, but it is not known whether diet restriction accentuates or diminishes the hypertrophic response. Van Liere has employed the measure of heart weight versus body weight in guinea pigs as a determinant for the occurrence of cardiac hypertrophy (259). He reported that the ratio increases 55.8 percent above the sea level value and varies with altitude above 12,250 feet. Valdivia determined that a progressive hypertrophy of the right ventricle occurs in guinea pigs which are exposed to a simulated altitude of 18,000 feet (257). This hypertrophy stabilizes after six weeks and no further enlargement occurs. In x-ray tech: tude native increase i1 21.3 percer 53 as 4,000 f rate in an humans (10 is still n chemorecep instrument Ca \ incl-gages nOrmaI Wit AltMush t Strughold that led t in agnte h greatEr va which in ti In Chronic 0f Cardia Viduals ( in respon 53 In man, Kerwin (150) and Rotta (220) have used x-ray techniques to study the heart size of high alti- tude natives of Peru. They have measured an average increase in transverse heart diameter of from 11.5 to 21.3 percent over sea level controls. Heart Rate: Changes in elevation of as little as 4,000 feet can cause a significant increase in heart rate in animals, but the rate is usually unchanged in humans (10). The mechanism of a change in heart rate is still not known, although most theories focus on the chemoreceptors of the carotid and aortic bodies as being instrumental in this response (269). Cardiac Output: In anoxic hypoxia cardiac output increases rapidly in many species, then returns to near normal within a few days as blood hemoglobin increases. Although the mechanism is not fully understood, in 1940 Strughold (243) conducted the first convincing study that led to the current predominant hypothesis. It is thought that epinephrine and norepinephrine are liberated in acute hypoxia which cause an increased pulse rate, greater vasoconstriction and higher arterial pressure, which in turn cause the heart to beat more forcibly. In chronic hypoxia, no difference from sea level values of cardiac output has been noted in acclimated indi- viduals (10, 269). Coronary blood flow also is increased in response to hypoxia. Th conditions natized in declines, and carbon and oxygen Because of abnormal, 5‘5 the ind resting at 350cm3 per molecules The Partia is redUCec‘ The difqu Per inSpif amount 8% the total OXYQEn is the prima: of diminig rESpOHSeS at high ajl (67), and S4 Lung The respiratory rate increases in high altitude conditions, following even moderate exercise by unaccli- matized individuals. Arterial saturation by oxygen declines, as do the partial pressures of alveolar oxygen and carbon dioxide. The minute volume, tidal volume and oxygen consumption all increase in hypoxia (213). Because of oxygen want the breathing patterns become abnormal, but tend to return to a less-abnormal state as the individual becomes acclimatized (269). Man resting at sea level has an oxygen requirement of about 350cm3 per minute. At 11,300 feet the number of oxygen molecules per unit volume is reduced by one-third. The partial pressure of oxygen at the alveolar level is reduced from 96 mmHg to 64 mmHg (alveolar hypoxia). The diffusing capacity of the lung limits oxygen uptake per inspiration to about 20-25 percent of the total amount available. Hyperventilation occurs and increases the total oxygen inspired. Hypoxia exists when pulmonary oxygen is below body needs. Von Muralt suggests that the oxygen requirement at the tissue level should be the primary criterion for studies concerning the effects of diminished oxygen pressure and the compensatory responses of the body (274). The oxygen consumption at high altitude has been shown to increase 11 percent (67), and up to 32 percent (76), over sea level values. ‘7' I. negaly and Pul cattle, pigr and cats (1 calves do r to high a1: typoxic at (223). AIM Holstein c: reactive t, the breed ; of all the adapt to h, GaStl'Oihte AW 0f hemic’ Sta dition the: EffeCts ORI Grately re (so), In We 18,0 diminutiOn Th in rats Wa the degree 55 Pulmonary hypertension associated with cardio- megaly and cardiac failure is often observed in man, cattle, pigs and rabbits but is rarely seen in lambs and cats (10, 215). Bisgard et a1. determined that calves do not hyperventilate during acclimatization to high altitude (21). As a result, calves are more hypoxic at altitude than is man who does hyperventilate (223). Among the breeds of the bovine species, the Holstein calf has a pulmonary bed which is highly reactive to acute and chronic hypoxia. This renders the breed more susceptible to right heart failure, and of all the bovines, it displays the poorest ability to adapt to high altitude. Gastrointestinal Tract and Accessory Organs Of the four distinct forms of hypoxia (anoxic, hemic, stagnant and histotoxic), it is the anoxic con- dition that has been most studied with respect to its effects on the alimentary tract. Anoxic hypoxia mod- erately reduces gastric motility in man (126) and dog (60). In the normal, trained dog, simulated altitudes above 18,000 feet produce a loss of gastric tone and a diminution in the strength of hunger contractions (261). The effect of hypoxia on gastric emptying time in rats was demonstrated as an increase proportional to the degree of hypoxia and was not related to hypocapnia (reduced 0 earlier st‘ due to 11qu In threshold 8,000 feet Again, the Proportion and relati 0f the res considera'; Percent of Anether St Simulated emPtYing ShggeSt t‘ sihCe it '1“ in the ra (l) the 1‘ tracts, a the gastr “ant at t suggeStee. 56 (reduced carbon dioxide in the blood) (58). In an earlier study an inhibition of gastric emptying time due to hypoxia could not be demonstrated (179). In dogs, Van Liere and Stickney showed that the threshold for elevated gastric emptying time lies at 8,000 feet, under simulated altitude conditions (262). Again, the time required for the stomach to empty was proportional to the degree of hypoxia. This threshold and relationship has also been found to be characteristic of the response of man to hypoxia, although there is considerable variation among individuals (13.2 to 166.9 percent of the normal value for emptying time) (258). Another study has shown that the exposure of man to a simulated altitude of 12,500 feet or, to a true ele- vation of 15,000 feet, resulted in delayed gastric emptying times (231). The results of these studies suggest that the phenomenon should be studied further, since it may have a major effect on nutrient utilization. The mechanisms of delayed gastric emptying time in the rat, dog and man can be summarized as follows: (1) the low oxygen partial pressure stimulates vagal innervation of the pyloric sphincter, which then con— tracts, and (2) severe hypoxia will then directly affect the gastric musculature. Both stages reflect oxygen want at the tissue level. Another mechanism has been suggested, supported by the investigations of Van Liere et a1. (26 The hypoth emptying t secretion similar ef Un in the bio experimend blood Volt hunger cor time (268) E) aSSOCiateg or propuls inhibited “3°"?- (26c no signif; conditiom Ia effects 0: detested’ in cardiac with the 80 one ounce mo mmsmo ho mmsouw zoom CH massage mo mmoq 0>Humaoaso .6 .82 181 ucoafiummxm may no woo oov omm oom omm oom oma ooa om ll 0 o comma \\ cowumucmEonmsm x1! 0 Hmuocwe \. \ \ h \.\ \\ .\. \.\ \ squeep 30 zeqmnu eArqunmno mmmmmflc n X \ Hmowmmom u. . I momsoo Ham "0 \ mocmm mo \ coauwameoo L .~ .m .6 I .5 .m .m .3 .3 .2 .3 .3 .3 .3 .S .2 .3 182 ucmfiflnmmxm on» no moo poo comma mo mmsmo mo msouo Home: mop ca mHmEHcé mo mmoq o>flumadfido om OOH.“ 183 oov 0mm com ucwEfiuwmxm can no man omN P com F omH ooa om Hmowmhnm u o ommomwo u x monomo .38 no rod #3 uNH squeep go Jequmu eAraeInuma 184 ucmafiummxm oou mo moo pom gamma «0 mmsmo mo mdouo Hmaoq may ca mHmEHc¢ mo mmoq o>flumasadu om omflm 185 ‘\ "\ oov 0mm oom ucofiaummxm on» no moo 0mm 0 com om.” 00H amounmhnm u o mmmmmflo u x womsmo Has no yea IHH .3 squeep go Jaqmnu eArqunmna 186 There were nine deaths attributed to physical or traumatic causes, either from falling over the cliff or into a deep ditch. Four of these deaths occurred below the cliff. Three other animals slipped down in an area of the cliff that was less steep, but were prevented from plummeting the full distance by sliding into an irri- gation trench having a depth of about three feet. This also occurred once to the author during the process of extricating one of the steers from this trench. All three animals survived and gained weight, although one of them subsequently died of pneumonia on April 19, 1973. The five deaths following falls into the deep ditch were due to a broken neck and consequent destruction of the spinal cord, to suffocation caused by severe bending and pressure in the neck, or due to a combination of both causes. Several animals survived after falling into the ditch because they landed in a position which did not cause severe distortion of the neck. None of these animals were able to extricate themselves. Several workers were required to remove them from the ditch. None of the post-mortem examinations revealed displaced abomasums, which could have predisposed death from digestive disorders at a later time. Apparently the animals fell off the cliff or into the ditch while they were grazing. Several steers were observed grazing near the cliff and continued to 187 graze as they moved downward on the increasingly steep area. Those steers that fell must have grazed them- selves beyond a point where they could maintain their footing. The other steers fell into the ditch either as they grazed or while trying to jump across it. In the former situation, much of the opening of the ditch along its length was covered with small brush, to an extent that made it difficult to know where the pasture ended and the ditch began. There were some small spaces where the ditch was discernible and animals tried to jump it. Some steers were able to jump across the ditch, whereas others either died or survived the fall. Those that died landed head-first in the bottom of the ditch, indicating they must have grazed their way into it. The steers that survived the fall were usually on their backs when discovered, indicating that they attempted to jump and nearly reach the other side, but slipped backward and slid to the bottom of the ditch. Sur- prisingly, none of the survivors broke their legs or pelvis. After a gentle slope had been dug to where they had fallen, they were righted and able to walk out on their own. There were seven deaths from falls in the upper group and only two in the lower group, whereas the mor- tality due to disease was evenly divided between the lower and upper groups. The length of the cliff exposed 188 to the steers was about twice as great for the lower group, yet only one steer in the lower group died by falling over the cliff compared to three in the upper group. One steer in the lower group died in the ditch compared with the same demise for four steers in the upper group. The length of the ditch exposed to the upper group was nearly twice that of the lower pasture. All deaths from physical causes occurred during the night when visibility was poor and the herdsman was not watching the steers. During the first three months of the experiment heavy rains prevented the building of fences to reduce losses from falling. The loss of the first steer from a fall over the cliff occurred on the forty-second day of the trial. By the end of the rainy season, four steers died, two by falling off the cliff and two in the ditch. The need for extensive fence installation was recognized early in the trial and, after lengthy negotiation, the materials were received and fence- building began in late August, 1973. A period of nearly seven weeks was required to install an adequate fenceline in the critical areas. One steer of the upper group died during the period of fence construction and only one animal died from a fall over the cliff after the fence was installed. Six of the ten deaths due to disease occurred during the rainy season. 189 The mean body weights of all animals that died before the end of the experiment are shown in Table 22. This is the "intermediate" group of steers and the data illustrate that smaller, rather than larger animals, were more susceptible to death. Six steers died before a second body weight measurement could be made, there- fore no change in body weight could be calculated. One steer died the night following the first weighing of the second weighing period, providing only a single observation. This steer plus the remaining twelve steers survived long enough to calculate average daily gain prior to death. There were small differences in ADG and the absolute values are too small to indicate that significant changes in body weight occurred prior to death, regardless of the cause. Table 22 Mean Initial Body Weights and Average Daily Body Weight Change Prior to Death of Steers Not Surviving the Experiment Average Daily Mean Initial BW (Kg) BW Change (gm) Cause of Death Lower Upper Lower Upper Group Group Group Group Disease 159 (5)a 198 (5) -9.5 (4) 1.7 (4) Falling 157 (2) 210 (7) ---- (0) -5.5 (5) aFigures in parentheses are the number of steers in each category. 190 In summarizing the mortality encountered in this experiment several factors are evident. The number of deaths due to disease was the same at both altitudes. Although the lengths of the cliff and the ditch to which the steers were initially exposed were about equal in both pastures, many more steers in the upper group died from falls than in the lower group. The deaths of all animals regardless of cause occurred in a period of 376 days of a possible 384 days, an average of one death approximately each twenty days. The deaths from all causes were grouped into four distinct periods (Figure 4). Eight of the nine deaths due to falls occurred before fencing was completed. Six of ten deaths due to disease occurred during the rainy season, whereas the remaining four fatalities occurred during a two-month period in the latter half of the dry season. It must be remembered that the "dry season" is a relative term because conditions in the paramo remain cold and damp during this time. Precipitation continues but is less than during the rainy season. In addition, the winds are very strong during the dry season which adds to the stress on the livestock grazing there. Another feature of the data is the greater mean body weight of the animals that died from falls versus those due to disease. The larger animals were more aggressive while grazing and tended to graze a larger area than did the smaller steers. 191 It is evident from the data that the management of animals in the conditions of this experiment must include adequate fencing and supervision of livestock movement. In addition, rigorous health measures must be employed for the prevention, early diagnosis and the cure of disease. A major observation was the absence of severe brisket disease. There was some gross evidence of edema and jugular vein pulsing, but these symptoms were never severe and none of the animals displayed all of the symptoms of even moderate brisket disease. It may be that the disorder is debilitating, and perhaps fatally predisposing, in Ecuador, but the classical symptoms probably are not sufficient for early diagnosis of the disease. To the extent that it was observed in this trial, brisket disease is not a major deterrent to the utilization of the paramo for meat production using the male Holstein. Hematocrit The mean hematocrit values for all analytical groups of steers and fifteen "control" animals are pre- sented in Table 23. The control animals were milking cattle and yearling heifers which were raised and main- tained at 10,000 feet of altitude, the elevation of the Dairy Research Center. Control samples of the steers were not taken before the beginning of the trial because of a lack of sampling equipment. 192 .Amo. v ov uzonouuno mancoonuflzmwm one :Eznoo a swoon: muownomnoozm oadu mcnnooo manoZO .Amoo. v ov uconouunu anacoonuncmnm one cfiznoo a Genoa: muonnomnoozm oaom mznnunm dado: n .GOflUflerOU ”HMUCUUN H GGMO§ 0H” MOSHQ> Add” In In o.oo.m n m.mv o.ob.o n v.om o.oohm n m.m¢ ..o.ns.m n v.om I: van m.m n «.mv m.a n «.mn 0m.v n «.mw on.v n «.mv 0m.v n m.vv oh.v n m.nv II onw m.v n o.av m.m n h.mn om.n n o.av on.w n m.ov om.n n o.Hv o~.v n m.ov II and II II II II II II. H.m H v.mm II uuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuu u ezno> Haoolooxomo omoucoonoo ozone ozone ozone ozone ozone ozone noooD no3oq noooD nozoq noooz no3oq ozone uzoswnooxm oumwwwmwouan mnooum n2 ozone dunno nonucou no one monnomoume Hmowumauzd oonne on mnooum one maofiazd Honuzoe coouuao no mozao> unnooudaom zoo: MN oHnoB 193 The normal hematocrit (packed cell volume) range of mature bovines (Bos taurus) is 30.3-34.9 ml/lOO ml blood with a mean value of 32.4 m./100 ml blood (55). The hematocrit usually declines with age in low altitude conditions. The hematocrit value of the control group was higher than that of sea level conditions (55) sug- gesting that an adjustment to 10,000 feet of altitude includes elevation of the hematocrit which is maintained during exposure to this elevation. All groups showed a significant increase in hematocrit during the experiment. The changes in hematocrit of the steers in the final group were significant for each period. There were no significant differences between the treatment groups on each sampling date although the mean hematocrit value of the upper group was consistently higher. This suggests that the measurement of hematocrit was not sufficiently sensitive to detect differences due an average altitude increment of 1,150 feet between the two groups. Under normal altitude conditions the hematocrit tends to decline as age increases, being highest in the first weeks after birth in the bovine. In addition, the hematocrit increases after initial exposure to altitude regardless of age, then stabilizes at a level higher than that at the lower level after a few weeks of exposure. Neither of these phenomena occurred in this 194 trial. Age and hematocrit were positively correlated at each sampling of the upper group and at the last sampling of the lower group (Table 24). The slightly negative correlations on the first two samplings of the lower group became positive at the end of the trial suggesting that hematocrit was increasing as rapidly as age. The mean hematocrit steadily increased through- out the trial rather than stabilizing after acclimati- zation was complete. The change in hematocrit during each period for both groups was closely related with the number of days in each period. The data suggest that the change in hematocrit was fairly constant throughout the trial and had not begun to stabilize by the end of the experiment. Table 24 The Simple Correlations (r) of HematocritVersus Age in the Final Group of Steers Sample Date Lower Group Upper Group July 10, 1973 -.29 .51 Oct. 17, 1973 -.02 .31 Mar. 12, 1974 .07 .49 The body weight data indicated that survivability favored the heavier animals which, under normal experi- mental conditions, should have resulted in lower mean hematocrit values than those observed, due to a normal 195 decline in hematocrit with age. This interaction should have resulted, at least, in no change of mean hematocrit during the trial, and might have yielded a decline during each period. The blood samples of the steers after 139 days of adjustment to higher altitudes yielded a small increase in the mean hematocrit of both groups compared to the control value. After 238 days there was a significant elevation of the hematocrit which may be accounted for, in part, by continuing stress. The rise in packed-cell volume between the second and third samplings, however, indicates there must be other factors operative in the polycythemia, because there is a limit to which the hematocrit can increase without deleterious effects. These effects include excess viscosity and osmolarity which could alter the normal processes of metabolism, electrolyte exchange and oxygen diffusion to the tissues. The increase in hematocrit between the first and second samplings, when an unbalanced mineral mixture was irregularly offered, was significant for both treatment groups and changed at a rate of 0.034 percentage units daily. The hematocrit increased by 0.039 percentage units per day from the second to the third sampling. This daily increase of hematocrit was 13.4 percent greater than during the first period. The accelerated increase occurred at a time when it would be expected 196 that hematocrit should have stabilized. This period corresponds to the time when the balanced mineral mixture was regularly offered. Perhaps this mixture caused some of the increased erythropoiesis by providing necessary erythropoietic nutrients. Another explanation could be that excessive mineral intake increased the osmolarity or viscosity of the blood. The metabolic benefit to the animal of continued increases in erythro- cytes was not explained by the body weight data, because increases in average daily gain were not proportional to the change in hematocrit. It is not suggested that ADG is highly correlated with hematocrit values but low hematocrit could limit metabolic efficiency. The con- tinued increase in hematocrit was due, only to a small extent, to the need for more oxygen to support body weight gains. A principal question concerns the exaggerated increase in hematocrit at a time when lower values than those measured in the trial, and stabilized levels, would be expected. Polycythemia can occur directly through stimulation of erythropoiesis and from the early and transient release of red blood cells from splenic storage in response to hypoxia. It can occur indirectly by a loss of blood water, blood serum or plasma which results in a net decrease of blood volume and a consequent increase in red blood cell volume per 197 unit of extracellular blood fluid. Total blood and blood fluid volumes were not measured in this trial. A change in this component may have occurred contributing to the elevation of hematocrit. It is not known whether a change in blood fluid volumes could occur sufficiently, without metabolic detriment, to be the primary cause of such high hematocrit values. The continued increase of the number of red blood cells indicates the need for elevated oxygen transport, exceeding the increase normally expected at the altitudes included in the experiment. Perhaps there was a direct stimulation of red blood cell production, or indirectly there may have been toxic factors that excessively blocked oxygen-binding by hemoglobin. Additionally, oxygen trans- port across the pulmonary system may have been reduced, or oxygen uptake may have been partially inhibited. Blood Minerals The concentrations of macroelements and micro- elements in blood are often used as indicators of the mineral status of the organism under study. In many instances, assuming the human or animal is not under severe stress, these values can aid in the assessment of mineral status. Changes in blood mineral concentration related to dietary treatment offer insight into the mineral status of the organism under investigation. However, at best, the sampling of a single tissue or 198 blood can rarely provide a complete understanding of the mineral status. Complete mineral status can only be determined by measuring the minerals in other tissues and in the diet. This is a costly method requiring the study to focus more on mineral status and less on the practical aspects of production. This trial was designed to obtain some perSpec- tive of the mineral status of steers subjected to high altitude stress and poor quality feeds, to the extent that analysis of minerals in a single body component, blood, could provide basic information. Serum mineral concentrations are a classical measure in the research literature and permit some comparison of the values measured in this trial with data compiled under "normal conditions." However, just as the values in one tissue limit the assessment of mineral status, so does the lack of previous information on the mineral content of feeds, water and animal tissues at high altitude in Ecuador reduce the ability to understand completely the mineral metabolism of the experimental stresses. This section of results will discuss blood mineral concentrations and how they compare with mineral levels determined in countries other than Ecuador, but in similar production situations. Altitude is a factor of this trial which is not a variable affecting the analyses from other locations. Little information exists 199 on serum mineral levels in bovines at high altitude. The effects of altitude on mineral requirements have not been established. Normal, sea-level values for some serum minerals also may be "normal" at altitude but the stress of the environment and hypoxia may increase the requirements for other minerals. A high serum mineral value at altitude, compared with the "normal" concentration at sea level, may indicate that the requirement for the circulating or mobilized mineral is higher than at sea level, or storage may be inhibited as a consequence of the diet or environment. A low serum mineral value may be "normal" at altitude because of increased uptake by the tissues or due to a true deficiency in the diet. These concepts illustrate some of the difficulty in interpretation of the blood mineral content of animals in conditions for which few data exist on mineral levels and requirements. Serum Calcium Concentration: The serum calcium contents in all analytical categories are presented in Table 25. Of most interest are the serum calcium values for the final group of steers. The treatment differences due to altitude were not significant in any analytical category for any of the three sampling times as deter- mined by analysis of variance. As the experiment pro- ceeded, there was a decline in serum calcium concentration which was most pronounced in the lower group but none 200 noonoHMflo manzooflmnzmnm ono noflnomnoozm oEMm ozu mcflnmom zEzHoo m on memo: .COnnmw>oo unaccoum n 3o. v E ”swoosn mzooe ono monzmnm Hams III: III: III: 11:: van m.~ « mm.m~ m.o n h>.mm v.m n m.mh m.~ n o.mn mmm ~.H n oa.h~ m.m n om.m~ m.HH n m.mh «.ma n o.mm and ozone ozonooenoqu o.om.~ n Hm.v~ oto~.m n Hm.~m m.ma H «.mm v.oa n m.mm «mm oh.m n Hm.m~ om.m n mv.n~ m.HH n m.mm m.HH n b.mm mmm oh.~ n N>.>~ o>.m n m~.w~ m.HH n m.mm a.oa n «.mw mma mnooum Had oeom.m n Hm.v~ oenm.m n Hm.- m.ma n v.mm v.oa n m.mm emm om.m n mh.mm 0m.m n mm.b~ o.mH n m.mm m.HH n m.mm mmm om.m n va.mm ov.m n mm.h~ N.HH n H.mm mH.oa H «.mm mma ozone Hocno IIIIIIIIIIIIIIIIIIIIIIIIIIIIIII EooIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII ozone noooD ozone no3oq ozone noooD ozone nosoq uzoEHnooxm coaumnnzoozoe Eznmocmmz eznom zonumnuzoozoe eznoaoe Eznom mo oumo ozone uzofiuoona com mnomonme Hmowumamcd on mCOHnonuzoozoe Eznmocmmz com Ezfioame Eznom mm oHQoB 201 of the measurements were statistically significant. Normal serum calcium concentration is in the range of 90-120 ppm in the bovine (55). The values measured in this trial ranged from 59.9-112.4 ppm with an overall mean of 86.2 ppm. Because the mean was below the normal range and the forage contained less than one-half of the requirement, the mineral supplement included an adequate supply of calcium in the form of steamed bone meal. The supplementation began after the second sampling, but appeared to have no beneficial effect on raising the serum calcium to normal levels. Calcium is essential for bone growth, blood clotting, cardiac function, enzyme activation and membrane permeability. Severe calcium deficiency can retard skeletal development and reduce growth. Combined with a phosphorus deficiency, a low intake of calcium can cause weak bones with consequent fracturing, stiff joints and lameness. Lameness can diminish growth by reducing appetite and restricting the movement necessary for grazing. Forage and soil levels of phosphorus were low in the experimental area. The forage phosphorus level was only one-fifth the requirement for growing steers (199). The calcium deficiency in the forage, combined with the severe phosphorus shortage and the reduced dry matter intake aggravated the calcium:ph08phorus 202 relationship and produced a severe deficiency of both minerals. The need for supplemental calcium and phos- phorus exists in the best animal production systems except where the major portion of the dry matter intake is satisfied with high quality legumes. It is evident, because of the deficiencies noted above, and because of the absence of legumes in the paramo, that supplementation of calcium and phosphorus is necessary in amounts in excess of those in typical cattle production schemes. Both calcium and phosphorus are stored in the body. Ninety-nine percent of the calcium and 80 percent of the phosphorus is stored in the skeleton (255). Only a small amount of each mineral is in solution. There- fore, body reserves serve to protect the organism from periods of deprivation of these minerals and permit the maintenance of levels in the blood. In steers consuming normal amounts of calcium and phosphorus, circulating levels of these minerals would not be expected to change considerably if the animals were deprived of the minerals for a few weeks. The animals in this trial maintained serum calcium below the normal range for the length of the trial. The mineral was supplemented at a level that entirely met the requirement for calcium, regardless of the forage content of the mineral. Surfeit feeding of calcium did not relieve the slight deficiency of the 203 mineral in the blood. It is possible, although unlikely, in the conditions of the trial the need for calcium was below requirements established under more intensive cattle production systems at low altitude. It could be considered further that 86.2 ppm of serum calcium is the "normal" level at the altitudes of the experiment. But, most steers displayed gross signs of skeletal deterior- ation as the trial progressed. These signs were most evident in the shoulder area where moderate to severe "winging" occurred in steers of all ages and did not appear to be relieved by mineral supplementation. Lameness in the joints and weak backbones were also observed in many animals. The above observations suggest that even with adequate calcium and phosphorus intake the availability of these minerals was low or absorption was partially inhibited. The high fiber content of the forage and/or an unknown compound may have bound a sufficient quantity of the minerals pre- venting efficient utilization. The mean serum calcium concentrations of the nonsurvivors were notably lower than those of the steers that survived the experiment. However, four of the twelve nonsurvivors from which blood samples were obtained died from physical causes. It is difficult to relate all types of death in this trial with low serum calcium, but it may have played a predisposing role. 204 Serum Magnesium Concentration: The results of serum magnesium analysis are presented in Table 25. The serum magnesium levels of all steers and the final group were similar on the first two dates but were notably lower at the third sampling. Preliminary analyses indicated that magnesium levels were above normal. Therefore, no supplemental magnesium was included in the balanced mineral mixture. The normal range of serum magnesium in bovines is 19.4-26.7 ppm with a mean of 21.9 ppm (55). The range of serum magnesium concen- trations of this trial was 17.27-36.26 ppm with an overall mean of 26.69 ppm. Only three of 105 determi- nations were below the minimum normal value of 19.4 ppm, all of which occurred in the lower final group of steers at the last sampling. In addition, fifty-four of the 105 analyses were higher than the maximum normal value of 26.7 ppm, and were divided evenly between the lower and upper groups. The effect of altitude was not sig- nificant at any of the times of sampling. There was a statistically significant (P < .01) decline in serum magnesium concentration in the lower and upper groups from the first to third and second to third samplings. The serum magnesium content of a male steer at 10,000 feet was 21.0 ppm, which was in the low side of the normal range, but was apparently sufficient for growth. 205 Magnesium distribution and metabolism in the body is closely associated with calcium and phosphorus levels. The skeleton and teeth contain about 70 percent of the total body magnesium. The remainder is distributed in fluids and soft tissues and is important in enzyme activation and central nervous system function. According to the results of this trial, none of the steers were severely hypomagnesemic at any stage of the trial, although three steers were slightly below normal at the end of the experiment. Only four steers had serum magnesium values slightly higher at the third sampling than at the second sampling, indicating there was a notable decline of serum magnesium in the other steers at the end of the trial. The nonsurvivors con- tained lower serum magnesium concentrations than the survivors but the values were above the normal mean. The deaths in the trial were not related to serum mag- nesium content although, as the experiment progressed, the concentration of serum magnesium declined. It is possible that steers grazing the paramo for a period several months longer than the twelve and one-half months of this experiment may achieve a hypomagnesemic state which could be prevented or cured by magnesium supplementation. The dietary requirement of bulls for magnesium at low altitude is 0.08 to 0.1 percent of the dry 206 matter. The forage consumed in the experiment had a magnesium content of 0.040-0.056 percent on a dry matter basis. The slow rate of growth of the steers, compared with higher growth rates obtained under ideal conditions, reduced the need for magnesium. The decline of serum magnesium content at the end of the trial, combined with the observation of skeletal degeneration, indicates that magnesium reserves may have become depleted after twelve and one-half months of grazing in the paramo. Hypomagnesemia, as a result of consuming gala §g_péramo for a long time, and the hyperexcitability which accompanies low serum magnesium levels, may be masked by the lethargy common at high altitude. Therefore magnesium supplementation may be necessary for steers that are expected to graze in the péramo for periods greater than one year. Without supplemental magnesium the steers could reach a point at which magnesium might become a major factor restricting growth. Serum Sodium Concentration: The serum sodium concentrations in the three analytical categories and two treatment groups are presented in Table 26. With the exception of serum sodium in all steers of the upper group, the sodium concentration was lowest at the end of the trial than on the other two dates, but in all cases sodium was highest on the first sampling date and 207 .Amo. v ov noonoumno manomonmnzmnm .Aao. v ov econommnp mHnCMUHMflzmnm m.mv m.hm m.mb N.vw m.hv m.mh m.mo H.vm +l +l +l +l +l -H +l +4 o.¢em m.mem ¢.mhm m.¢mm m.~mm v.mhm m.Hmm H.0mm m.mm m.me v.mm m.~m o.mm m.mm +I +I +l +l +l +l +l 'H N.hmm m.~mm m.ehm H.Hmm H.v>m m.mhm m.mmm h.mmm .QOHUMH>0U UHMUGMUm .IT MCMQE 08a. MHM ono nonnomnoozm oEom mzwnozm zEzHoo m zH memo: ono noflnomnoozm oeom mznnmom zEzHoo o zfl mzmozo t.e mozao> dado em.men h n.nsnm we.mme e m.mnem en.mn~ h n.emem we.om~ e o.oe~e on.eom h o.emmm on.emm H n.~eem em.ene e n.emmm an.~nm h m.meem o.em.nem h e.mmmm 0.8m.mmm h e.mnmm n.eom h o.emem n.5mm h n.~eem m.mmm e m.n~em m.ee~ h m.meem k.mee h k.mmmm he.nmm h “.memm «mm mmm and ozone onmwooenoqu vwm mmm mma mnomum nn< «mm mmm mma (mmone Hocflo IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII EoolIIIIIIIIIIIIIIIIIIIIIIIIIIIIII ozone noooD ozone nozoq ozone noooD ozone no3oq conuonucoozoe Ezflmmmuoo Eznom cowbonnzoozoe ezfloom Eznom ozoEHnooxm mo moo ozone nzoEuoonB poo mnomonoe Hmonumaozd on mzowuonuzoozoe Ezfimmmuoo one eznoom Eznom mu oHQoB 208 significantly greater than subsequent measurements for all steers and in nonsurvivors. The normal range of serum sodium in bovines is 3,130-3,550 ppm with a mean of 3,300 ppm (55). The range of serum sodium concentrations in the trial was 2,702.5- 5,346.9 ppm with an overall mean of 3,741.5 ppm. The wide range of values observed in this trial may be due to the wide range of body weights and ages of the steers. This would reflect variable metabolic needs. In addition, the selection of forages during grazing may also vary with the age of the animal which could notably affect the intake of sodium. The high overall mean of serum sodium concentration suggests that the intake of sodium was sufficient for metabolic needs. Sodium is involved in the metabolism of water and the control of nutrient uptake by cells. A dietary deficiency causes a loss of appetite, decreased growth, loss of weight and an unthrifty appearance. Although the steers in this trial had depressed appetites, low body weight gains and rough hair coats, the serum sodium levels suggest that these characteristics were not caused by a deficiency of sodium. The decline of serum sodium concentration during the trial suggests that dietary intake of the mineral was insufficient to maintain previous levels. The steers consumed low quantities of forage, yet the 209 forage sodium content was similar to legumes which are usually higher in sodium than common forage grasses. Even with reduced forage intake the sodium consumption appeared sufficient to maintain adequate blood levels of the mineral. The serum sodium concentrations for March, 1974 were determined after the steers had received the balanced mineral mixture for 104 days. The mineral supplement had little effect on mean serum sodium levels. The rate of decline of serum sodium concen- tration in the final group of steers from the first sampling to the second was approximately twice as great in the upper group as compared with the lower group and about 50 percent greater from the second to the third samplings. The daily decline of serum sodium in both the lower and upper group from October, 1973, to March, 1974, was only 30-40 percent of the rate from July to October, 1973. This suggests that either an equilibrium in sodium metabolism was being reached or that the mineral supplement had a positive effect on reducing the rate of decline. It is possible that mineral supplementation permitted the serum sodium levels to approach normal concentrations, making more sodium available for tissue utilization. Inadequate sodium intake early in the trial may have reduced tissue stores of the mineral in favor of maintaining adequate 210 circulating levels. The most definitive conclusion is that sodium status approximated that of sea level steers and there was a sufficiency beneficial for normal metabolism. The concentration of sodium in the serum of a male Holstein at 10,000 feet of altitude was 6,600 ppm (0.66 percent) and in the whole blood was 6,200 ppm. This value is twice both the normal sea-level value and the concentration in the blood of steers exposed to the two altitudes of this trial. Because of the wide range of serum sodium measured in the trial the high sodium concentration at 10,000 feet of altitude does not indicate that the concentration declines with altitude. The levels of sodium in the serum of the steers that subsequently died from various causes (Table 26) were variable, yet close to the normal range found at sea level. The data indicate that the deaths of these steers were not closely related to deficient or excessive serum sodium concentrations. Serum Potassium Concentration: The serum potassium concentrations for the three analytical cate- gories and two treatment groups are presented in Table 26. Serum potassium values were highest at the second sampling for all steers and the final group. There were no significant differences among the serum 211 potassium concentrations. The normal concentration of potassium in bovine blood at sea level ranges from 190- 260 ppm with a mean value of 230 ppm (55). The range of values in the trial was 281.3-538.2 ppm, with an overall mean of 381.5 ppm. There were no significant differences due to treatment or with time of the experi- ment. The mean concentration of potassium in the trial was 65 percent greater than the sea level value. Potassium is important for cardiac function and the maintenance of osmolarity of body fluids. Potassium deficiency is characterized by retarded growth, emaci- ation, reduced appetite and decreased digestive effi- ciency. The body is tolerant of wide ranges of potassium concentration, with sodium partially replacing depleted potassium levels and the kidneys rapidly excreting the mineral when present in excess. Hyperkalemia is often seen during renal insufficiency, alcoholism, low protein intake and negative nitrogen balance. The hyperkalemia measured in the experiment may result from a combination of factors. These include renal insufficiency due to altitude and/or the low protein content of the principal forage. The forage contained potassium at about one-third of the sea-level requirement of 0.7 percent of the ration dry matter (199), suggesting that the excess serum potassium was not due to high dietary intake of the mineral. There 212 was little effect of mineral supplementation with potassium on serum concentration of the mineral. The concentrations in serum were similar before and after treatment. The mean serum concentration of potassium in the steers that died was equal to that of the sur- vivors, indicating that death was not closely related to serum potassium status. There are other possible sources of dietary potassium. The steers may have consumed small quantities of other forages that contained high levels of potassium. The water may have contained enough potassium from soil leaching to meet the requirements of the steers for the mineral. The potassium in the mineral supplement was sufficient to meet entirely the dietary requirement. Serum Iron Concentration: The analyses of blood for serum iron concentration are presented in Table 27. Normal plasma or serum iron content in bovines is in the range of 0.92-2.70 ppm. The range of values in this trial was 6.21-24.07 ppm with an overall mean of 12.35 ppm for all steers and 12.23 ppm in the final group of steers. The mean of nonsurvivors was 12.89 ppm. There were significant differences in total serum iron due to altitude at the time of the first sampling. The highest values were obtained at the second sampling and were sig- nificantly greater than the first and third measurements. 213 Amo. .Amo. v ov noonoMMHo MHDGMOHMflzmnm ono nonnomnoozm oEom mznnonm son m ca mcooz . COflfiMwammu UHMUQM#$ v ov noonoMMflo maucooflunzmnm one noflnomnoozm oEom mznnonm zEzHoo m cw mcooz Msmswoo Q mzooE on» one mozao> dado IIII IIII IIII IIII «mm H.mm n m.mam m.n n o.mv~ mo.v n em.va om.a n Ho.ma mmm m.>ea n H.mmv m.vma n m.mov me.v n mm.HH vv.m n Ne.HH mmH moone onmnooEnoucH mm.moa n e.bmm Um.mh n m.mnm mmm.m n me.oa meova.~ n mv.m «mm oo.m~H n m.vm~ «.mma n o.mmm w.omm. n mv.va moa.m n mo.ma mmm m.ov.hma n m.mmv om.HwH n o.nhm omm.m n em.oa ovm.¢ n ma.ma mma mnoonm Ham om.moa n e.nmm 0m.mw n m.mnm omm.m n mv.oa oeuvH.N n Ne.m «mm 0m.hmH n v.v>~ e.nma n >.Hmm eeooa.m n mm.ea opm.m n mo.ma mmm o.o~ had + e mav 0m mud + o onm 0.3mm a + OH OH o.omm m + me ma mma .mwone Hozwo IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII EooIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII ozone noooD ozone noBOA ozone noooD ozone nozoq ozoEnnooxm mo moo zonH zHoonOEom zonH Eznom monnomouoe Hoonnmaozd oonoB nae now zonH ozzoolcaooHeoEom com um odome zonH aznom mo macanonucoozoe U. 214 The absolute values of total serum iron are of interest because they are from two to eight times greater than the upper limit of the normal range. Serum iron normally accounts for l to 3 percent of the total iron in the blood and is the transport form of iron in the body. At low altitude the binding capacity of serum transferrin for iron in the male bovine ranges from 33 to 38 percent (254). Thus, the serum has the potential to contain 2.5-3.0 times the normal concentration of serum iron. That the potential binding capacity of serum iron may have been reached in this trial can account only partially for the high levels measured. It is ' possible that partial hemolysis of the samples occurred during transport and storage, which released hemoglobin- iron from the erythrocytes, and caused an elevation of serum iron. The serum iron concentration in male steers maintained at 10,000 feet of altitude was in the range of 3.5-4.0 ppm, which is two to three times greater than normal sea level values. Some of the excess serum iron may be attributable to high levels of iron in the soil and for water. The steers could have consumed iron directly from the soil while grazing. The forage was not analyzed for its iron content, but the high serum iron values indicate that it also may have been adequate 215 in iron. It is possible that the steers consumed small quantities of other forage having high iron content. Concentration of Hemoglobin-bound Iron: The analyses of whole blood for content of hemoglobin-bound iron are presented in Table 27. The decline in concen- tration of this element bound to hemoglobin was highly significant (P < .05) from the first to last measurements in the lower group and from the first to subsequent samplings in the upper group. The normal range of hemoglobin-bound iron in bovines is 374-408 ppm (55, 75, 184). The hemoglobin of most mammals contains 0.34 percent iron. The hemo- globin content in the blood of bovines is in the range of 11-12 gm/lOO ml (55, 75). The range of hemoglobin- bound iron measured in this trial was 99.8-654.7 ppm, with an overall mean of 337.8 ppm. The hemoglobin content of blood rises with altitude. A concurrent rise of iron bound to hemoglobin would be expected. In this trial the hemoglobin-bound iron was slightly below the sea-level value. The iron concentration at the high altitudes of this trial was notably below the expected values. This deficiency, however, may have been compensated for by the extremely high levels of serum iron. Leakage of iron from the red blood cells into the serum may have occurred, accounting for the 216 excess serum iron and for some of the low concentration of hemoglobin-bound iron. The variability was great within treatments and was not correlated with mortality or body weight gains. Only two of the forty-one steers sampled had hemoglobin- bound iron values that remained above the minimum normal concentration. One of these two steers had normal iron levels at two samplings but died before the last sampling. The mean hemoglobin-bound iron concentration of non- survivors ranged from 33 percent below the lower value of the normal range to 13.5 percent above the upper value of the normal range. Thus, hemoglobin-bound iron status was not correlated with mortality. The data suggest that several animals may have been marginally iron-deficiency anemic. However, the considerable variability of the body weights and ages of the steers probably accounted for the greater part of the wide range of hemoglobin-bound iron values. The data do not confirm that there was a serious iron- deficiency anemia in steers grazing the paramo. Summary of Blood Iron Content: The serum iron concentrations of the survivors in the lower and upper groups were significantly different (P < .05) after 139 days of exposure to the respective altitudes of the experiment. In addition, mean serum levels in all 217 animals were notably higher than sea-level values throughout the trial. The hemoglobin-bound iron concentrations were variable and considerably below sea-level normal levels. The hemoglobin content of the blood would be expected to rise notably due to the need for increased oxygen transport due to the hypoxia of high altitude. Because of the constancy of the iron content in hemoglobin, this is often used as an indicator of hemoglobin status. The low levels of iron bound to hemoglobin in this trial suggest that hemoglobin was not significantly elevated above normal values. However, past research shows a definite increase in hemoglobin in men and animals exposed to high altitude. The expected increase in hemoglobin in this experiment was not detected by the analysis of hemoglobin-bound iron. The data do show that iron-deficiency was not a significant limiting factor for survival and body weight gain. The relative proportions in the blood of serum and hemoglobin-bound iron were about normal, with the latter being the principal form of iron in the blood of mammals. The correlations between the two forms of iron were relatively high, being highest at the second sampling (Table 28). This is in agreement with the normal relationship of iron distribution in the blood. The high correlations suggest that individual changes 218 in serum iron were proportional to the changes in hemoglobin-bound iron. Table 28 Simple Correlations (r) Between Serum Iron and Hemoglobin-bound Iron in the Final Group of Steers Day of Experiment Lower Group Upper Group 139 .373 .66 238 .84 .78 384 .60 .51 aCorrelation coefficient Concentrations of Other Microelements in Serum: Serum was analyzed for copper, cobalt, manganese, zinc and selenium. The normal serum levels of these micro- elements are below the minimum level of detection by the analytical instruments that were available. From these analyses it could not be determined with certainty that there were deficiencies of the above minerals in the experimental animals. Summary of Blood Analyses: The analyses of blood minerals and hematocrit before and after mineral supple- mentation in the final group of steers are summarized in Table 29. Although the lower and upper groups had significantly different serum iron concentrations at 219 the first sampling, this difference did not continue in the subsequent samplings. Concentrations of the minerals in blood declined after mineral supplementation. There were slight declines for calcium, sodium and potassium whereas notable reductions in serum iron, hemoglobin- bound iron and magnesium were noted. Table 29 Summary of Blood Analyses of the Final Group of Steers (Lower and Upper Groups Combined) Before and After Mineral Supplementation Mineral Supplementation Blood Percentage Measurement Before After Change Mean Concentration (ppm) Calcium 87.7 86.9 - 0.9 Magnesium 28.26 23.57 -16.6 Sodium 3807.4 3638.7 - 4.4 Potassium 383.4 377.7 - 1.5 Iron 13.82 9.84 -28.8 Hemoglobin-bound iron 348.0 282.7 ~18.8 Hematocrit (%) 42.6 50.0 17.4 The relationship of calcium and magnesium is of interest in grazing cattle. Hypomagnesemic tetany (grass staggers) is associated with low serum magnesium and calcium. When these levels are sufficiently below normal, the animal's movements are stiff and staggering can occur, similar to the difficulty of movement observed in some of the steers in this experiment. Within a few hours or days of the initial signs, violent 220 convulsions develop and death can occur rapidly unless the animal receives subcutaneous or intravenous injections of magnesium sulfate. Clinical signs can be observed when serum magnesium levels are 10-17 ppm (normal range is 19.4-26.7 ppm). Symptoms are certain to occur when concentrations of serum magnesium below 10 ppm are maintained. Almost all occurrences of the disorder are accompanied by a serum calcium concen- tration at or below 66 ppm (normal range is 90-120 ppm). The disease is often characterized by sudden and unexpected death. There were gross signs that mild hypomagnesemic tetany may have occurred in the trial. Chronic hypo- magnesemia is characterized by a stiff gait and a gradual loss of condition that can occur for several weeks with- out affecting appetite or body weight gain. This dis- turbance is often followed by spontaneous recovery or by the acute form of tetany. It is difficult to recon- cile the blood levels of calcium and magnesium in this trial with even mild hypomagnesemic tetany based on a comparison of the "normal" levels of these minerals. However, it is possible that the metabolic requirement for calcium and magnesium may be elevated at high altitude. This would cause the observed levels to be low relative to the required concentrations, causing at least a mild hypomagnesemia detrimental to production. 221 The magnesium and calcium contents of the forage were only a fraction of those found in typical forage grasses. Because the dietary intake of these minerals was low,. an extensive mobilization of calcium and magnesium from skeletal stores had to occur to maintain the blood con- centration. Continued depletion and a low rate of mobilization of these minerals could retard growth over a long period of time. Serum sodium concentrations remained slightly above to normal levels throughout the experiment. The pica, i.e. a craving for salt, observed during severe and prolonged salt restriction in cattle, was not observed in this trial. Other research at high alti- tude indicates that little change in serum sodium con- tent occurs (140, 146, 269). The serum potassium concentration of steers in this trial averaged approximately twice the normal level. Early studies indicated that either serum potassium levels were depressed (84) at altitude or there was no change (140). However, recent research has demonstrated that with a constant potassium intake at 14,100 feet of altitude, humans show a decline in urinary potassium and an increase in serum potassium (146). This is a net retention of potassium upon exposure to hypoxia and may be a protective mechanism beneficial to oxygen uptake, but it is counter-productive to the need for [Ll 222 increased urinary electrolyte excretion caused by the alkalosis produced by hypoxia. The excessive levels of potassium in the serum of the steers in this trial were a normal response to hypoxia but the concentrations were not high enough to reduce the growth rate. The iron status of the blood in the steers of this experiment was unexpected. Mean serum iron concen- trations were two to three times normal values. Hemoglobin-bound iron concentrations varied considerably, both greatly above and below normal levels. The mean concentration was below normal. This was unexpected because hemoglobin-bound iron is highly correlated with blood hemoglobin content which increases with altitude. Despite low total iron concentrations in the blood, the increased transport form of iron in the serum may have prevented severe iron deficiency anemia, permitting normal metabolism of the element by the tissues. The continued increase of packed-cell volume in the blood during the trial was unexpected. An initial elevation of this blood component is expected in response to hypoxia, followed by a stable level sufficient to sustain the oxygen requirements of the steers. A long- term erythropoietic stimulus caused a steady increase in polycythemia. The initial response can be accounted for by the release of splenic reserves of red blood cells. 223 In summary, the serum mineral concentrations of calcium, magnesium, sodium, potassium and iron were not sufficiently different from normal values to have been major limiting factors to growth under the conditions of this trial. The low levels of iron in hemoglobin suggest that the hemoglobin content did not increase. Hemoglobin concentration per red blood cell may not have increased but, due to a considerable increase in the total number of red blood cells, total hemoglobin may have been elevated. Forage Analysis The native forage is the primary source of nutrients for livestock maintenance and production in the high altitude grasslands of Ecuador. The concen- trations of organic and inorganic constituents of the forage are among the several determinants of the live- stock production potential of the native forage in the area. Dry matter consumption, which is related to palatability of the forage, combined with the nutrient density and proportions of nutrients, can provide an estimate of the utility of the grasslands. This trial was designed to estimate the nutrient yield of the paramo by measuring the growth of animals grazing the native herbage. The area was representative to the extent that the predominant forage of the site 224 is Stipa Ichu. The nutrient yield could have been measured by periodically cutting and weighing small areas of the pasture and analyzing the forage. This method is imprecise for estimating potential animal production. It is difficult for the investigator to select a sample having a botanical composition and maturity equal to that consumed by grazing animals. The forage analyses of this trial provided additional information on the nutrient quality and quantity rela- tive to typical forages used in low altitude dairy production systems. Although normal requirements of nutrients for high altitude production have not been established, the analyses provided a basis for compara- tive nutrition. Proximate Analysis and Total Digestible Nutrients of Paja de Paramo: The proximate analysis and TDN of the principal forage in the paramo is shown in Table 30. Samples of young and mature gala were collected on four different dates. The dry matter content declined with maturity, but not significantly. The concentrations of crude protein and lipids (ether extract) increased as the plant matured. Concentrations of crude fiber and ash did not change significantly in the young plant, while the former declined with maturity and ash steadily increased. The changes in nitrogen-free extract (NFE) 225 «.mm ~.mv m.me m.HH m.~ H.mm m.m m.om mn\m m.am H.mv m.mv v.oa >.H m.mm o.m «.mm mh\m H.~m H.5e m.mv m.oa n.a m.mm m.m o.vm mh\o “onmo onzuoz n.mm m.me H.mv m.oH o.~ m.mm m.m n.Hm mh\m n.oe e.om e.me m.e o.~ «.mm n.m m.nm me\m IIII m.nv v.me H.oa m.a m.mm m.m v.em mn\~ umfloo.mzzow IIIIIIIIIIIIIIIIIIIIIIIIIIIIIII ommuzoonooIIIIIIIIIIIIIIIIIIIIIIIIIIIII 9. one. “New we“. we... new. mflmom nounmz one o no oeonwo MW owmo onznoz ecu mzzow mo AZQBV muzonnnzz oaowumomno Hmuoa woo AQSQV mnnaflonumomno nouns: one .mamhaozd ouoEflxono om oHQoB 226 reflected the changes in crude protein and ether extract. The high crude fiber content was at or above the highest crude fiber values observed in the better forages at their most mature stage, yet was slightly lower than the content of crude fiber in cat and wheat straws (199). The total digestible nutrient content of the forage was similar at both stages of maturity and con- siderably below the values of higher quality grasses. Steers consuming normal amounts of dry matter generally need a diet containing about 50 percent TDN to meet their maintenance requirement. The steers in the exper- iment were able to meet their maintenance requirement and also gained body weight from forage containing less than 50 percent TDN. This suggests that the TDN require- ment for growth was less at high altitude than at sea level. On the contrary, it is likely that the TDN requirement for energy was greater in the conditions of the experiment because of the almost daily rains and near-freezing temperatures during the night. If the maintenance requirement for TDN is, in fact, higher at altitude the steers must have consumed far greater quantities of forage than observed by similar cattle at low altitude grazing quality pastures. This does not seem likely because the condition of most of the steers was poor. They appeared thin until receiving the mineral supplement and spent much of the time lying 227 down and grazing sporadically when they were standing up. Therefore, the dry matter intake must have been reduced below normal. The above observations indicate that the equations for calculating TDN may not include factors that are related to the high altitude conditions of this trial. The crude protein content, even at the highest value of 8.8 percent, is at or below that of most grasses at the stage of greatest maturity when protein levels are low. Mean crude protein content is higher in the young than mature (paja_dg,paramo), but the difference is not commensurate with the differences in stage of maturity between the samples. The changes in nutrient content (Table 30) do not represent completely the true differences due to stage of maturity. The samples were taken randomly from several locations in the experimental site. Each composite sample was collected from similar locations on each sampling date, but no two serial samples were taken from the same plant. The stage of maturity was based more on the comparative stage of growth of young plants versus that of mature ones, and less on the stage of maturity related to initial stages of growth. Thus, the data provide some information on the nutritive value of the principal forage in the paramo, but are of little value for determining seasonal changes in nutrient composition. 228 Forage Digestibility: Table 30 includes the in_gitrg_dry matter digestibility (DMD) of the gala, according to the method of Tilley and Terry (251). The mean DMD for young paja was 18 percent greater than mature 2313, but the highest digestion coefficient of 40.1 was considerably below that of grasses commonly used in cattle production, such as mature bromegrass, ryegrass and bluegrass. The iglvitrg_organic matter digestibility (IVOMD) of 2212.92 paramo is presented in Table 31. The value is the mean of four samples taken from the experimental site for the development of laboratory techniques which were included in the thesis research of another investi- gator in the Nutrition Laboratory (203). These data are presented for comparison and provide additional infor- mation on the chemical composition of the paja_g§'paramo consumed by the steers in this trial. The organic matter digestibility of the forage was lower than the total dry matter digestibility. This, combined with a low organic matter content makes the forage a poor source of energy for rapid growth of cattle. Cell-Wall Constituents and Ash, Silica and Nitrogen Content of Paja de Paramo: These analyses, obtained from research at INIAP (203) are presented in Table 31. The values for wheat straw are presented for Iii—i 229 Table 31 In Vitro Organic Matter Digestibility, Cell-Wall Con- stituents, Silica, Ash and Nitrogen Content of Paja g3 Paramo and Wheat Straw Chemical Composition b,c as a Percentage of AnaIYSiS the Dry Mattera Paja de Paramo Wheat Straw IVDMD 35.72 i 3.73 ---- IVOMD 29.88 i 0.02 25.70 i 0.77 NDF 72.14 t 1.51 81.58 i 1.43 ADF 47.70 t 0.63 56.76 i 0.69 ADL 6.97 i 0.68 10.75 t 0.73 Silica 9.11 t 0.36 5.72 t 0.05 Ash 10.50 i 0.03 8.25 i 0.03 Nitrogen 0.64 i 0.02 0.71 i 0.03 aAll values are the mean of four samples except for IVDMD (five samples) 2 standard deviation bIVDMD = In vitro dry matter digestibility; IVOMD = in vitro organic matter digestibility; NDF = neutral detergent fiber; ADF = acid detergent fiber; ADL = acid detergent lignin cAll values derived from reference (203) except for IVDMD [I \I\I I‘llllllllllllll.| 230 purposes of comparison. Wheat straw is generally con- sidered a poor source of nutrients for animal production and is marginally able to satisfy maintenance require- ments. The data in Table 31 include the percentage of the indigestible dry matter that is accounted for as total fiber (neutral-detergent fiber), lignocellulose (acid-detergent fiber), lignin (acid-detergent lignin), silica (a residue in ADF) and total ash, of which the major mineral in most grasses is silica. The data illustrate that paja.aayparamo is similar to wheat straw in its fiber fractions, is superior in organic matter digestibility and inferior in nitrogen content. The latter measurement, extrapolated by using a factor of 16 percent nitrogen in crude protein, estimates that 2213.92 paramo contains 4.0 percent crude protein, whereas the level in wheat straw is 4.4 percent. A silica content of greater than 2 percent depresses digestibility at the rate of three percentage units of digestibility for each increase of one per- centage unit of silica (4). Thus, the gala aa paramo, containing about seven percentage units of silica above the threshold, has a reduced digestibility of about 21 percent compared with a similar forage with less than 2 percent silica. 231 These data illustrate that the principal forage consumed in this trial was of poor quality and that the productive potential of the paramo in its natural state is limited, in part, by the scarcity of high quality forage. Mineral Content of Paja de Paramo: Table 32 presents the mineral content of two composite samples of young paja_and one composite sample of mature paja. Both the calcium and phosphorus content was significantly lower than that of many of the common forages such as ryegrass, bluegrass and bromegrass. The concentration of potassium in paja was only 5 to 10 percent of that measured in the common grasses. The level of sodium was comparable to that in forage legumes and grasses. The magnesium content ranged from one-tenth to one-fourth of the concentration measured in most forage grasses. The cobalt concentration was more than twenty-five times greater than the levels in legumes and cereal grains, which are usually higher in cobalt than are grasses. There is a wide range of normal manganese contents in most forages which is higher in forages growing in an acid soil such as that of the param . The manganese content of paja_was in the upper half of the normal range. The c0pper content was approximately one—half the value of most forages. Zinc was present in paja at concentrations similar to legumes, which are usually [ll 232 Table 32 Mineral Content of Paja aa Paramo on a Dry Matter Basis 2/73 9/73 9/73 Mineral Units ——————— -——————— (young) (young) (mature) Calcium % 0.13 --- --- Phosphorus % 0.04 --- --- Magnesium % 0.04 0.047 0.056 Sodium % 0.09 0.141 0.209 Potassium % 0.21 0.282 0.314 Copper ppm 6.0 --— ___ Cobalt ppm 4.0 I<4.0 ‘<4.0 Manganese ppm 5.0 435.0 302.0 Selenium ppm -- ‘<100.0 <1100.0 Arsenic ppm -- <40.0 <40.0 Molybdenum ppm -- <40.0 *<40.0 Zinc ppm -- 4.0 19.0 Chromium ppm -- <4.0 ‘<4.0 l1 233 much higher than forage grasses. The minimum detectable levels of selenium, molybdenum, chromium and arsenic were above the normal levels measured in plants. There- fore, the presence of deficient or toxic concentrations of these micronutrients could not be established. Summary of Forage Analyses: The principal forage consumed by the steers in this trial was low in protein, TDN, fat and digestibility and had high contents of fiber and ash compared to the common forage grasses. The pro- tein and TDN levels were apparently not low enough to prevent body weight gain. Also, they were not suf- ficiently high to permit the higher rates of gain possible in steers consuming good quality forage. The steers could gain body weight under the nutritional and environmental stresses of the experiment. This suggests that the forage is not devoid of nutritional merit and can make some contribution to the energy needs of cattle grazing solely on paja aa param . The ability to utilize forage at high altitude is species-dependent. For example, the ability of the alpaca to digest the pro- tein, fat and fiber of forage is much greater than for sheep (9). The TDN of the same feed at high altitude is 15 to 30 percent higher in the alpaca than in the sheep. The ability of the bovine to convert poor quality roughages to meat at high altitude may be limited. 234 There were severe deficiencies in the forage of calcium, phosphorus, magnesium and potassium, There was only one-half the normal level of copper. Excesses were noted for sodium, cobalt and zinc. Although the analysis was imprecise, there may have been some selenium toxicity, but this was not observed during the trial. Just as urea may have been beneficial to growth rate, a mineral mixture, balanced to provide the mineral requirements of the steers, should enable efficient metabolism and utilization of the forage consumed. Even the highest quality forage can be inefficiently utilized if the mineral status of the animal is unbalanced. Soil Analyses The mineral content and pH of two composite samples of the lower and upper pastures are presented in Table 33. The interpretation of the mineral status of the soils was made by the Soils Laboratory of INIAP. Potassium, copper and zinc were present in normal amounts in both soils. Nitrogen was high in the lower soil and normal in the upper pasture. Both soils had excessive levels of calcium, magnesium and iron. There were deficiencies of phosphorus and manganese in the soil. The pH was slightly acidic but within the normal range. 235 Table 33 Soil Mineral Content and pH of the Paramo Pastures Soil Measurement Lower Pasture Upper Pasture Calcium (ppm) Iron (PPm) Potassium (PPm) Magnesium (PPm) Phosphorus (PPm) Nitrogen (PPm) Manganese (PPm) Zinc (ppm) Copper (ppm) pH 600 126 105 100 8 68.0 12.0 7.6 4.0 5.6 625 108 105 105 10 55.0 13.5 7.2 3.2 5.6 One difficulty encountered in the interpretation of soil mineral data in Ecuador is the relationship of local concentrations to established "normal" values. The soil chemists there have monitored the soils of the sierra for several years and have determined the contents of soil minerals in many areas. But the interpretation of whether the concentration of a particular mineral is low, medium or high is based on data of soil, plant and animals established elsewhere, few of which are derived from areas having soil of volcanic origin. INIAP has only recently begun studies to determine "norms" of mineral requirements of native species of plants and animals, of soil fixation, the effect of organic matter 236 content and the ratios of inorganic to organic phos- phorus. As norms are established for the local conditions interpretations of mineral status will become increasingly relevant. For example, although phOSphorus concentration in volcanic soils is low, if its availability in the soils of Ecuador is greater than elsewhere, the soil content could remain below that of established norms yet be sufficient for plant and animal production. Much more research is needed to define more precisely the nutrient status of soils, plants, animals and humans. A good example of the "state of the art" of interpretation of mineral status in Ecuador is the role of magnesium in the soil-plant-animal relationship. The analysis of soil magnesium led to the interpretation that it was present at a high level. But this level did not produce excessive plant uptake, because the magnesium in the forage was only a small fraction of that found in most forage grasses utilized at low altitude. The extremely "low" plant magnesium level should have led to severe deficiency of this element in the animal consuming 2212.92 paramo. On the contrary, the serum magnesium concentrations were in the upper portion of the normal range. The requirement for magnesium may be lower at high altitude, but this remains to be deter- mined. Perhaps the availability of magnesium in the plant is considerably greater under the conditions of 237 the experiment, to an extent that provides adequate utili- zation of the mineral. Also the magnesium may be in forms more readily absorbed by the gastrointestinal tract of the animal. The steers probably consumed mag- nesium in enough soil and water to maintain adequate levels of the element in the serum. The soil pH of 5.6 lies in a normal range of pH 5.5-6.5. The availability and solubility of soil minerals such as calcium, phosphorus, magnesium, man- ganese, zinc, iron, cobalt and boron are greatest in organic soils having a pH of 5.0-6.0. Below pH 7.0 the availability of molybdenum is low especially in organic soils. Most soil minerals in this trial should have been highly available for incorporation into the paja_aavparamo, although some were present in low quantities in the soil. Mineral Interrelationships The mineral interrelationships of most interest in this trial may include calcium-phosphorus-magnesium, copper-molybdenum-sulfate and magnesium-potassium. The availability of calcium and phosphorus in the soil has long been known to be interrelated. These minerals are also interrelated in uptake by the plant and in the nutrition of the animal. In this experiment the high calcium level in the soil was not reflected in the 238 plant content, yet the steers were only mildly hypocalce- mic. The low accumulation of calcium in the plant may reflect of low soil phOSphorus. The moderate hypo- calcemia was a result of depressed intake of forage as well as its low calcium content. High soil magnesium can depress calcium incorporation by the plant. Low plant and blood phOSphorus combined with relatively high calcium intake can reduce cellulolytic digestion in the rumen. The normal magnesium, low calcium and possibly low phos- phorus in blood may have played a major role in the skeletal deterioration noted in the steers after several months of grazing a forage having low levels of all three minerals. A depressed intake of forage low in phosphorus could have aggravated the nutritional stress. A high phosphorus diet normally increases the magnesium require- ment. Because the intake of phosphorus was low the mag- nesium requirement probably was not elevated. A prolonged intake of forage having low calcium and magnesium content could lead to hypomagnesemic tetany. If this state developed at all in the trial, it was neither debilitating nor was a cause of death. The copper-molybdenum-sulfate interaction can only be speculated upon in this trial because the levels of these minerals in blood were not determined. Moly- bdenum and sulfate can prevent the toxicity of copper by reducing its concentration. The binding of copper 239 by molybdenum compounds and sulfate in the soil and plant also makes copper less available to plants and animals, especially the ruminant. The results of unpublished experiments at INIAP suggest that soil and plant sulfur may be low. This, combined with the lack of diagnosable copper deficiency or toxicity in the present experiment, suggests that the nature of the relationship of these three minerals was not a deleterious factor for the growth and survival of steers in the param . Magnesium and potassium are interrelated both in soil and in animals. A magnesium deficiency can occur in soils having high levels of potassium that interfere with magnesium uptake by plants. The data indicate that this was not a factor in the trial. A high intake of potassium by animals can decrease magnesium absorption. This also did not occur in the trial, because potassium intake was low and magnesium blood levels were in the normal range. The high potassium content in the blood apparently had no deleterious effect on magnesium con- centration in the blood. The opposite situation, low potassium and above-normal magnesium in soils and ani- mals, usually does not interfere with normal plant uptake or animal metabolism. Iii 240 Mineral Supplementation Supplementing the diet of the steers with a mineral mixture balanced to meet the requirements for normal growth at low altitude resulted in dramatic increases in the rate of daily body weight gain, despite a decline in serum mineral concentration. The decline may have been caused by increased tissue storage and/or utilization of the minerals. It is possible that increased excretion occurred due to alkalosis produced by hypoxia. On the other hand, depletion of body stores of some minerals may have occurred prior to mineral supplementation. The additional mineral intake may have prevented a severe depression of serum mineral content toward the end of the experiment. The inclusion of urea in the mineral supplement may have been a significant factor in the dramatic increase in rate of gain. The steers were consuming a nitrogen- poor forage in which the ratio of protein to calories was wider than required for normal productive performance. The mean crude protein in the forage was 6.4 percent. Based on a mean body weight of 300 kg just prior to mineral supplementation, a normal dry matter intake of 2.9 percent of body weight per day leads to a consumption of 8.7 kg of forage dry matter or 557 grams of crude pro- tein. The daily crude protein requirement is 745 grams for a 300 kg steer gaining 1 kg of body weight per day. H 241 Thus, there was a deficit of 188 gm of crude protein per day for normal average daily body weight gain. The mineral mixture contained 12.8 percent of urea. The mean daily consumption of the mixture was 340 gm per steer, providing an average of 43.5 gm urea daily to each animal. Using a protein-equivalent value for urea of 2.62, the intake of the mixture would raise the protein-equivalent daily intake by 114 grams. The total intake of crude protein, or its equivalent, from forage and urea should be sufficient to meet the requirements for a daily gain of 500 gm under normal circumstances. The maintenance requirements of all nutrients are unknown for high altitude conditions. It was estimated that dry matter intake by the steers was reduced to one-half the normal level. Even so, the urea content of the diet did not exceed 1 percent of the dry matter, above which urea toxicity may occur. Because the amount of urea provided by the supplement accounted for a large portion of the protein requirement, it is clear that urea played a major role in the increase of body weight gains. Molasses was added to the ration to improve pala- tability and assure the desired intake of the mixture. The molasses contributed about 2.6 percent of the mega- calories of net energy required for maintenance and an ADG of 1.0 kg for a 300 kg growing steer. Therefore, 242 the molasses played only a small role in the changes of body weight that occurred after mineral supplementation began. Based on the results of this study, male Holsteins not only can satisfy their maintenance requirements, but can achieve a moderate rate of gain with the native forage as the sole source of nutrients. aa libitum feeding of a mineral mixture, containing urea and balanced to correct deficiencies in the herbage, doubled the rate of body weight gain of steers. Although this is a major metabolic response, given the conditions of the experiment, the average daily body weight gains were low compared with those obtained in feedlot conditions at low altitude. This low metabolic efficiency in the paramo should be profitable, however, because of inexpensive labor, land and feed costs. Once the experimental site had been established the daily direct input costs of labor and minerals were (U.S. dollar equivalent) five cents and 3.5 cents per animal. The return from daily liveweight gain (based on an ADG of 212.5 gm in the final group of steers during mineral supplementation) was eleven cents, yield- ing a gross income over labor and feed costs of 2.5 cents daily per steer. Direct labor costs are essentially fixed within limits, i.e., one herdsman is required full-time regardless of herd size up to a limit which 243 was not approached in this study. Up to this limit direct labor costs decrease per animal as the herd size expands. Land costs have the same characteristic for small herds as do fencing and roads. Total costs of the supplement are essentially variable because they vary with the number of cattle being fed. The mineral cost per animal is related to body size because consumption depends on this variable. Observation of the Steers Several observations noted during the trial were difficult to quantify, yet they may contribute to an understanding of the nature and stress of the experimental conditions. During the month previous to being sent to the paramo, the original group of forty-eight steers and nine others were maintained in a pasture located just below the experimental site. This pasture ranged in altitude from 10,500 to 11,000 feet. All of the steers grazed normally, although the pasture was of only mod- erate quality. They showed normal vigor and few signs of stress. They were wary of humans but were not wild. Their hair appeared normal and showed no signs of mineral deficiency. Some of the younger steers became ill, however, and were not selected to be sent to the paramo. 244 Shortly after ascent to the paramo the steers became lethargic and the hair became rough on several animals. Many of the steers would lie down for long periods instead of grazing frequently. Most animals would rise when approached by humans but would make little effort to maintain a distance greater than ten feet. It was necessary for the herdsman to move con- tinually between groups to encourage the animals to graze the entire pasture at each altitude. The steers became less wary as the altitude increased, behaving as if in a stupor. As the trial progressed some physical deterior- ation became noticeable and the lethargy of the steers stabilized. Most steers were thin prior to mineral supplementation. After consuming minerals they filled out and appeared healthier and less lethargic. The most prominent change in many steers was a pronounced ”winging" of the shoulders. This was accompanied by drooping heads and sagging backs. At times some steers showed an unnatural gait when walking or running, which is best characterized as staggering. The lack of coordination was also evident when rising to graze was accomplished with difficulty. The staggering and difficult coordi- nation appeared sporadically for a few days and then disappeared. Some previously affected animals never displayed these signs later in the trial, while others 245 did. The degree and types of symptoms were highly variable with no apparent relationship to size, season or other experimental variables. The loss of steers over the cliff and in the ditch suggested that vitamin A deficiency possibly was causing night-blindness. All steers were treated with injectable vitamin A at 280 days of the experiment. Only one steer died from physical causes after this time. Fence construction was probably the major factor that reduced the number of deaths due to falling. The behavior of four animals in the upper group, consisting of one bull and three steers, was notably different from that of the others. All four animals survived the trial. After only a few weeks of residence in the paramo, they continually grazed in the upper half of the high altitude pasture and descended only for water and minerals. They were among the most vigorous animals of the trial and preferred to graze at an alti- tude at least 500 feet higher than the rest of the group. They often ascended to the upper limits of the pasture during the day. Their initial mean body weight was 294 kg, their final mean body weight was 328 kg. The ADG of these steers for the trial was 89 gm. A con- siderable amount of energy probably was expended during extensive grazing, which could account for their ADG being below the mean for the group. Their propensity 246 for grazing at high altitude may have a genetic basis, which is related to the ability to withstand the nutri- tional and environmental rigors of high altitude. This would permit the selection and breeding of cattle for maximum production at high altitude, which could sub- stantially reduce mortality and permit higher rates of gain under these conditions. CHAPTER V CONCLUSION AND RECOMMENDATIONS The government of Ecuador was interested in con- ducting research to determine if high altitude grasslands could be used as a resource for livestock production. Utilization of this area could expand the nutrient resource base of the country for meat and wool pro- duction. Thousands of newborn dairy males that could be raised in the paramo are presently slaughtered each year because the lack of perceived production alterna- tives. Vast areas of grasslands at high altitude are presently unused or under-utilized. Credit is available to support substantial expansion of agricultural pro- duction in the country. Conclusion The results of this experiment demonstrate con- clusively that Holstein cattle can grow in the paramo consuming only native forage and water. Appropriate nutrient supplements can enhance appreciably the growth of livestock grazing at high altitude. Disease control 247 248 and appropriate fence construction must be employed to reduce livestock mortality. Nutrient deficiencies affect livestock production at high altitude greater than does the reduced partial pressure of oxygen. Recommendations There is a need for additional research in the soil-plant—animal-human relationship to provide a basis for the economic development of the paramo for livestock production. These relationships are of most practical significance if improvement of the human diet is the ultimate target of changes in agricultural production. The primary research necessity is to investigate‘ thoroughly three nutritional aspects of livestock pro- duction at high altitude: (l) the metabolism of macro-elements and micro-elements; (2) nitrogen metabolism; and (3) the nutrition of young animals. Implicit in all research is exhaustive economic analysis of each experiment to determine the course of subsequent research and implementation of production practices. The mineral requirements for high altitude live- stock production must be established. This information will contribute to the knowledge of agricultural pro- duction at lower altitude in the sierra. This research will result in the formulation of apprOpriate mineral supplements and fertilizers for high altitude conditions. 249 Investigations of nitrogen metabolism should examine nonprotein nitrogen as a nutrient, as well as protein and its constituent amino acids. Nitrogen and mineral supplementation are metabolically interdependent and, when dietarily balanced, can improve the efficiency of total nutrient utilization. Investigations of calf nutrition from birth to six months of age should be emphasized. The younger steers in the paramo trial were unable to withstand the nutritional and environmental stress. Proper calf nutrition can provide healthy animals that will survive the transitions from lower to higher altitudes and from high quality pastures to the low quality forage of the param . A second major area of research in the paramo should focus on improvement of the forage. Fertilization studies and the introduction of legumes and grasses should be continued. Subsequent research should examine management of forage using pasture rotational systems with different animal densities. These agronomic studies can improve utilization of the available land for nutrient production. Nutritional studies and research on pasture improvement will provide a basis for investigating livestock production options in the péram . These options include the use of a combination of steers and 250 sheep, or cow-calf operations utilizing beef cattle breeds suited for high altitude conditions. A system of gradual transition of animals to high altitude should be considered. In addition, livestock could be sent to feeding centers for finishing prior to marketing. Steers should be marketed at weights below current standards to take advantage of the feed efficiency of the young animal. Large quantities of animals, homogeneous with respect to age, body size and breed, should be used to assess livestock responses. A wide range of ages and body sizes make it difficult to isolate the response of livestock to other experimental variables. These variables should include: A. Altitude--the cold, wet and windy conditions of altitude probably affect livestock performance more than a low partial pressure of oxygen. Shelters from wind and rain may be of benefit in the param . Because of the relatively narrow range of altitudes in the paramo, differences of altitude within this area need not be a major variable. B. Location--the climatic and physiographic diversity of the sierra is sufficiently great to require that similar research should be conducted in several high altitude locations. IF:- 251 The suitability of other areas of paramo for livestock production must be established. More information is needed before recommendations can be made for widespread utilization of these grasslands. A summary of the priority research needs for development of the paramo is outlined below: A. General Statement 1. In all studies, the confounding effects of altitude, species of livestock and species of forage must be isolated. For example, to study the effect of altitude the type of animal and variety of forage must remain constant. Economic analysis of all experiments is essential both for subsequent research and for adoption of production practices. Permanent meteorological stations should be established in the param . Nutritional Research 1. The determination of the mineral requirements and apprOpriate supplements for livestock in the paramo is of highest priority. Even the best of feeds are inefficiently used without a mineral supplement balanced to meet metabolic requirements. 252 The interrelationships of minerals in the soil-plant-animal-human sequence must be determined to understand the point at which mineral application is best utilized. For example, nitrogen may be applied to the soil to produce more forage, or nitrogen could be fed directly to the animal. Either one option, or the combination of two options, will provide the best utilization of scarce nitrogen resources. C. Pasture Improvement 1. Fertilization of the soils in the paramo should focus primarily on increasing the growth of the native forage. Pasture rotation can improve the harvest of the plant nutrients by livestock. Studies of animal density combined with pasture rotation will determine the appropriate stocking rate to best utilize the seasonal nutrient production of the param . Legumes and grasses adapted to high altitude must be studied under the conditions of the param . The establishment of forages higher in nutritional quality can reduce the need for costly dietary supplements. D. 253 Production Alternatives 1. It is essential that the nutrient production of the paramo be efficiently harvested. The following production systems should be investigated: a. Grazing of dairy steers, beef steers or sheep; b. A combination of cattle and sheep; c. Cow-calf Operations using beef cattle. The above production alternatives should include a system of fattening the offtake animals at lower altitudes prior to marketing. Studies must be conducted on the adaptation of livestock Species to the stress of high altitude conditions in the param . There are significant differences in adaptive ability both within and among animal species. Thorough investigation of the etiology and con- trol of disease is apparent from this study. The prevalence in Ecuador of most animal diseases is a limiting factor to improvements in livestock production. APPENDIX . .II Friar“): ._ .mEmanHnM one moznop anew emu emn eum eem eon uom aom eon mom emu nmu uau aau emu as nun mum nun eum aum umm mum mum uem emu uem nnm emu eon ea III III III III III III III III III III III euu euu auu ea see nee eee oee ene was eoe nee men eee «me ane nme eue ue mum mum nmn emm mam aem oem nem emm eum umm mum mnm eem ne aem can eem uem mam aam mam eem nem eem eem men oem emm ea III III III III III III III III eun eun uun emn nmn uen am III III III emn emn a n oen oen enn ann ann nen aen een em III III III III III III III III III III III eun eun aun mm III III III III III III III III uen emn amn aun aun emn nm men mam nem eem euu eum cum enm oau mau aeu aeu oeu emu em nuu nmu nuu euu aeu ean eou ean ean een man een ean een mu eeu eeu mmu emu onu een aan sen man ean ean uen uen aen au enu muu nuu ouu ueu enu enu mnu uan men een nan men umn mu euu euu euu enu ean sou ecu eou amn nan man man een ueu uu III III III aen men men men men een uen men men uen men ou use can umu eeu eeu eon oum aom mom emu mau emu emu emu en «en eeu emm umm mum amm eem uum eum uum num can amm emm nn neu meu oeu eeu neu emu emu aeu emu euu emu nuu eeu anu on enm enm enm anm enm enm enm aem enm uem anm nmu enm amm a sac oae aae oee one mne cue eee mam eem aem nan men men e aue mue ems mne nee eam eem mam amm nmm nmm emm nmm sea a see aee man eae eee see nee eme aee eee eoe one eee nee e III III III III III III III III III III III aen aen men n en un nn an eu en an en nn en a uu nu eu .oz H”: HMS HMS Gflh. >02 U00 #00 “.00 H55 _ Hflh H50 th th DOM .é monoo mznzmfioz zoom co mnooum mo ozone nozoq onn mo mnnmnoz Neon nozen>nUzH em XHQZmood oanoa 254 255 .meonmoamx one moznm> damn eoe aem mmm eem uem eam aam eam mmm mmm amm eem eem eem ee eeu eeu eeu aou een omn men men amn een men uen men man ee III III III III uue one eme mne ume nne eue mue ene eme me III III III III III III III III III III III uan nan men mm III III III III III III III III een men oen mmn mun mmn em III III III III um aen een men een een men uen een mmn em III III III III III III III III III III III eun eun umn mm III III III III III III III III III III III emm mem nem um III III III III III III III III aan ean ean ean aen men eu omu eeu emu m u euu mnu unu mnu anu enu mnu eou emn eou eu III III III III III een uen men een uen emn emn mmn uen eu III III III III umn umn uen nen omn een men een men een mu III III III III III III III III uan oan oan een men nan nu uum oum mmm unm eee aee eae mee one uoe moe ene uue mue mn mmu onm nnm uom eau oeu eeu meu mmu meu emu mom meu uom an oem mmm mem omm omm mmm eem emm eem uem eem aum eom eum en III III III III III III III III III III III uuu enu muu mn III III III III III III III III oeu mmu emu amu muu eeu en nam mam oem nem omm nem emm omm mmm aum mum mmm eum umm mn mmu emu euu auu enu nuu muu anu mnu enu enu emn nmn nmn un nee mee aee mee ene moe moe moe mem eam mam mam eam amm e eem eem emm aoe nem mem mem omm nem nem nem eem nmm ooe m unm enm anm enm emu emu mmu mom mom emu mmu meu eeu uom u mum aum mum onm omu eeu mmu eeu ueu uau eau meu eeu eau n mn un nn an eu en an en nn on m uu nu ou .02 no: no: no: can >oz moo uoo one new nso new nom nom omm .qa monmn mzmnmnoz some do mnoonm Mo ozone noooD on» no mnemnoz mwom nozem>mozH mm enema 256 0.5mm m.mmv H.Hmm N.~¢vm m.mmmm m.mwmm mo.HN Hm.eN Hm.m~ v.5m m.vn H.vh be m.oav o.Hmm m.¢mv N.NHmm m.omnm o.aomv oa.v~ mm.m~ vm.em m.om m.vh ~.mb we m.mov m.mov H.mHv m.oaov ~.ommm mevmm ov.e~ va.m~ mm.m~ v.moa H.mm h.mm we N.mmm H.dhm m.vmm m.me¢m H.0mwm m.~mhm hN.bH Hm.mm mm.e~ o.~m e.hw h.mm He 5.Hmm «.mvm m.Hmm m.monm m.mmmm mIHNHv mm.H mo.b~ mm.mm m.mm m.mm h.moH ov III III m.mov IIII IIII m.mmmv III III om.h~ II III m.vm hm III N.Nvm o.m~m IIII o.v~hm m.¢mmm III omIMN Hm.HN II m.om «.mb em III III v.e~v IIII IIII m.v~mv III III omIQN II III m.mm Hm N.omv m.vev v.m~v v.mmov OImohm o.aomv om.hN hm.mm hm.mm e.mm «.maa m.oaa om h.amm H.Hmm m.m¢m «.mmov m.mm>m mImomv mm.mm cm.v~ mo.m~ m.om o.Nh H.mm m~ h.mmm m.mNm h.ovm m.mvmm m.oaov «.momm ov.mN HN.NN on.e~ b.mm N.mm m.eh 5N e.Nom N.HHm o.va m.HNHq m.mH¢¢ ~.vmom ve.m~ mo.om Ho.m~ m.Hm N.m0H m.~m mm H.Hmm 0.0Hm m.HmN «.mmmm H.emvm h.mmH¢ om.NN NN.MN mm.mN «.mm m.on H.Nm NN III e.hmm v.mav IIII m.moam H.Nomw III mm.m~ NN.mN II N.hb N.mm om ~.0Hv «.mmm o.mvv N.vumm «.mmov H.~omv me.m~ eN.em vN.hN m.Hm m.mm e.hm ma v.aom m.mhm N.HHm v.mhom m.monm >.mmmm memH Hv.NN mo.m~ m.me m.mn H.mm HH A.ham o.vnm m.vwm H.m~dm m.mamm «.mmvm mN.mH om.hm mN.m~ v.55 «.mm H.mm 0H v.5Nm m.Nmm m.mmm N.NHmm «.mvem m.wm¢m NV.NN mo.m~ mo.Hm m.~a N.mm m.mm m m.vwv m.m~v m.moe «.mvmm «.mmmm m.mham mm.em mm.om HH.om H.mm H.mm H.vm m «.mem v.mwm m.bwm m.~o>m «.mmmm H.m~Hm AN.mH Ho.mN bBIQN m.mm H.mm m.om h 5.0Ae m.mmm H.Hmm m.mmmm o.mvmm NIMmHm Hm.eN ma.v~ mH.mN o.Hm o.mb o.mh e IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIEooIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII Na\n hH\oH oa\h ma\m nH\oH oa\h NH\m ba\oa oa\b NH\m hH\oa oa\h .oz .q< Eznmmmnoo Eznom fiznoom Eznom ezmmozmoz eznom Eznonoe Eznom ouoo monaoeom zoom :0 ozone nozoq oeu zn mnoonm mo Eznom on» an ezmmmouoo coo ezmeom .Eznmozmoz .Eznonoe mo moonnonuzoozoe mm oanoa l" 257 m.meu u.ene u.one n.uoem m.amoe m.oeme ee.eu em.mm em.mu e.ee e.oon e.ae ee m.nme e.mae e.ume a.emmm m.uuem e.momm mm.uu ao.nm em.eu e.ue e.om e.om ee III e.oem m.eem IIII m.memm u.emmm III au.eu em.eu III e.oe m.ne me III III m.mum IIII IIII m.meem III III un.eu III II m.me em III n.eom e.mne IIII e.unau m.eemm III no.uu mm.eu III m.na e.ae em III III e.ooe IIII IIII u.eoem III III en.eu III II m.ne eu n.eom n.eom a.unm m.auem u.ummm m.emmm oe.mu em.eu nm.eu a.mon e.om m.mm eu III a.nem n.nam IIII u.ueem u.emam III ae.au en.au III a.ne m.oa eu III e.moe a.mem IIII m.oenm o.euam III au.eu me.au III e.ua n.mm mu III III e.mne IIII IIII e.ummm III III um.au III II e.ae nu e.aem e.oem u.mem e.meem m.nmnm e.oaae mm.eu mn.om em.om e.mon a.mon e.em mn m.mum u.emm e.aem o.eeem o.eeem e.omee um.au em.mm me.um m.me e.om e.um an u.emm n.mm e.aem m.uuem m.muum m.omem mm.nu eu.om ma.mu e.ma n.me a.ee en III III o.nee IIII IIII m.amoe III III nm.eu III II e.me en m.aem u.enm u.uem e.mmam o.eeam e.mmme ae.eu ao.nm me.mu o.eon n.ae a.me mn a.unm e.mom m.mmu u.emam e.mnme m.meue ou.nu me.au no.mu n.ee e.em m.oa un a.enm o.eme a.ame o.eeem e.moam n.mmau ea.eu aa.mu mn.eu a.em e.ee e.ma e e.uam m.nme e.mem e.ummm o.eeem a.emmm mm.uu oe.mu no.mu e.me e.me e.me m a.oom m.mae e.aee m.memm a.eeue m.auem me.ou um.um ma.mm e.na u.em u.eon u a.oem e.mem n.nam e.oemm e.mmmm e.uomm ea.uu na.au ee.eu m.ma e.me m.oa n un\m anxon on\a unxm an\on onxa un\m anxon on\a un\m an\on on\a .oz .5 azmmmouoo Eznom Ezneom Eznom Eznmozmoz eznom Ezmoaoe Eznom ouoo monaofiom £00m do ozone noooD on» on mnooum mo Eznom on» an eznmmouoo one Ezneom .Ezmmozmoz .Ezmoaoe mo moonnonuzoozoe hm wanna 258 e.um m.mm m.mm m.mou m.mem o.enm ue.e ee.mn ea.en ae o.ee e.em e.am e.meu e.eue e.nem oe.a ue.en ao.eu ee m.mm m.me n.me m.omu e.neu m.mun am.e mo.mn ao.en ue o.ee m.em e.ne e.mnm e.ueu n.aem au.a ee.mn eo.on ne m.em e.ne o.oe m.een m.omn a.nen au.e ea.on ne.on oe II II m.em II II o.emu II II eu.on am II m.am o.em II m.emu a.eme II ao.en am.nn em II II n.me II II e.mau II II ne.on nm o.me e.me m.ee m.moe m.nan e.nmn ue.mn am.nn ee.mn om o.um e.ae a.ue a.mem m.uee e.ume me.on mu.an me.uu mu m.ee m.me e.ee m.oem e.umm e.mee ao.mn ee.mn mm.nn au u.me o.ee n.ee o.eau a.emn m.enm am.on ae.m ea.on mu o.ee e.ee a.ee e.unm e.num a.moe ue.e ea.on nm.nu uu II e.oe u.mm II e.meu a.mme II ee.mn ue.e ou m.ae e.oe e.ne e.aen e.neu a.ean au.e mm.en eo.on en e.mm o.ae a.um m.eeu m.mmm e.mee em.a on.nu em.e nn m.nm u.oe a.em a.omu e.ean e.eau mu.m mn.m mn.m on o.em e.em e.am e.nen m.oem e.aon mn.a mm.en me.e m e.ee m.ae e.ne e.eem n.ueu o.eee un.e nm.mn mu.m e o.ee e.me e.me m.onu a.amm a.mem mm.on mo.an eu.on a a.mm m.me e.mm a.emm u.umm m.uee ao.en eu.on eu.mn e unxm anxon on\a un\m an\on on\a un\m anxon onxa .02 con H . and meano> nneoIeoxomm oczooIcnoonmoEom zonH Eznom onoa monaoeom zoom :0 ozone no3oq on» on mnoonm mo ooonm oon cm oEzHo> mm oHnoB HHoeIooxomo omoncoonoo ecu zonH ozzoaIzmooamoEom woo zonH eznom mo mzomumnucoozoe H 259 e.ee m.me m.mv m.oam e.mma m.mHm mmIe mm.m au.e we o.H m.ae e.mm o.eov e.uam e.mmv mm.vH HmImH mm.~H vv II o.em a.ne II H.HH¢ m.oev II mm.ud no.ma mv II II o.hm II II a.emm II II mm.m mm II m.me m.me II m.enm m.mve II oe.a mm.vH on II II e.am II II h.ho¢ II II mn.m mm m.me m.me o.ee m.mm a.mom m.mmm me. ee.ma mo.m mm II m.ae e.am II m.mmm e.mav II N~.¢H mmIm em II m.me a.mv II ¢.vmm u.moa II «H.5H Hm.m mm II II m.mm II II OIBHQ II II hN.HN Hm m.me n.ae m.mm a.med a.mha e.avv mn.oa om.NH m¢.m ma a.ue n.ae m.oe m.mom m.mma a.mav mm.HH MNINH mNIOH ha e.am m.mm e.ae m.mwm e.mmm o.emm mn.m wN.mH ee.ma ea II II o.ee II II vIva II II om.MH vH e.mm m.mm 0.5m m.oma hImHH a.emm we.h au.a HvIQH ma H.vv m.me m.mm a.mvm m.enm m.mmv mmINH en.ea mn.oa NH m.me h.vm n.av m.mha m.mbm m.eNm mm.oa mm.ma vw.m w m.mm o.mv e.mv e.mom a.mmm m.mmv ee.ma ov.mH mH.0H m m.me a.ne m.me m.ahm a.mem NINNH Hm.HH MNINH vm.m N v.~m m.mv e.ae m.mmm H.Hmv e.mvm mv.m mn.ma mH.NH H NH\m hH\oa oa\b NH\m ha\oa oa\h NH\m hH\oa oa\h .oz GOHH C4 oezao> nHoeIooxooo zonH Eznom ozzooIznoonoEom onoo manoEom zoom zo ozone noooD on» om mnooum mo oooam oeu on oezno> Haoelooxooo oeonzoonoo oco zonH ozzoolzmQOHmOEom ozo zonH eznom mo ozonnonuzoozoe mm oHQoB LIST OF REFERENCES 10. LIST OF REFERENCES Abderhalden, E. 1902. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Adolph, E. F. and J. Goldstein. 1959. Survival of rats and mice without oxygen in deep hypothermia. J. Appl. Physiol. 14:599. Agar, W. T., F. J. R. Hird and G. S. Sidhu. 1953. The active absorption of amino acids by the intestine. J. Physiol. 121:255. Agricultural Research Service. 1970. Forage fiber analysis. Agricultural Handbook No. 379. H. K. Goering and P. J. VanSoest, Eds. Washington, D.C.: U.S. Department of Agriculture. Albrecht, E. and H. Albrecht. 1969. Metabolism and hematology at high altitude and the effect of drugs on acclimatization. Fed. Proc. 28:1118. Anonymous. 1974. Effects of high altitude. CSU Research 24(2):1. Archdeacon, J. W., J. T. Danforth and G. D. Dummit. 1954. Factors affecting bile flow in the rabbit and rat. Amer. J. Physiol. 178:499. Asmussen, E. and F. C. Consolazio. 1941. The circulation in rest and work on Mount Evans (4300 m). Amer. J. Physiol. 132:555. Baca A., S. F. y M. C. Novoa. 1963. Estudio comparativo de la digestibilidad de los forrajes en ovinos y alpacas. Revista de la Facultad de Medicina Veterinaria. 18:88. Lima, Peru: Univ. de San Marcos. Badeer, H. S. 1973. Cardiomegaly at high altitudes: Pathogenetic considerations. Aerospace Med. 44:1173. 260 ."'_"SI-Q.' .‘ Ira-A 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 261 Barach, A. L., M. Eckman, I. Eckman, E. Ginsburg and C. C. Rumsey, Jr. 1947. Studies on positive pressure respiration. II. Effect of continuous pressure breathing on arterial blood gases at high altitude. J. Aviat. Med. 18:139. Barach, A. L., M. Eckman, E. Ginsburg, A. E. Johnson and R. D. Brookes. 1946. The effect of ammonium chloride on altitude tolerance. J. Aviat. Med. 17:123. Barach, A. L., M. Eckman and N. Molomut. 1941. Modification of resistance to anoxia, with especial reference to high altitude flying. Amer. J. Med. Sci. 202:336. Barcroft, J. 1920. Anoxaemia. Lancet 2:485. Barcroft, J. 1925. The Respiratory Function of the Blood. Part 1. Lessons from high altitudes. Cambridge: Cambridge University Press. Bayeux, M. R. 1909. Influence d'un sejour prolongé a une trés haute altitude sur la temperature animale et la viscosité du sang. Comptes Ren- dues Acad. Sci. (Paris) 148:1691. Behar, M. and N. S. Scrimshaw. 1962. Effect of environment on nutritional status. Arch. Environ. Health 5:257. Berger, C. and O. Boje. 1937. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Bert, P. 1878. La Pression Barometrique. Paris: Masson. Bianca, W. 1969. Blood volume in young goats at high altitude. Fed. Proc. 28:1220. Bisgard, G. A., A. V. Ruiz, J. A. Will and G. F. Filley. 1972. Ventilatory response to acute hypoxia and chronic hypoxia in the calf. Fed. Proc. 31:389. Blake, J. T. 1964. Characteristics of brisket disease. Farm and Home Sci. 25(1):38. Logan: Utah. Agr. Exp. Sta. I . [I I, l ill II...) I. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. -"i . 262 I-‘ . ..—I. a. I Blake, J. T. 1968. Symptomatic treatment of brisket disease. Circular No. 150. Logan: Utah Agr. Exp. Sta. Blake, J. T. 1968. Occurrence and distribution of brisket disease in Utah. Circular No. 151. Logan: Utah Agr. Exp. Sta. Blume, F. D. and N. Pace. 1967. Effect of trans- location to 3,800 m altitude on glycolysis in mice. J. Appl. Physiol. 23:75. Blume, F. D. and N. Pace. 1969. Changes in the tissue distribution of glucose radiocarbon at altitude. Fed. Proc. 28:933. Blunt, M. H., M. Perry and R. Lane. 1970. The pro- duction of hemoglobin C by sheep at simulated high altitude. Res. Vet. Sci. 11:191. Bock, A. V., D. B. Dill and H. T. Edwards. 1932. Lactic acid in the blood of resting man. J. Clin. Invest. 11:775. Borsuk, V. N. 1949. Repression of ascorbic acid synthesis in rabbit under hypoxic conditions. Chem. Abstr. 43:4740. Britton, S. W. and R. F. Kline. 1945. Age, sex, carbohydrate, adrenal cortex and other factors in anoxia. Amer. J. Physiol. 145:190. Bronshtein, Y. E. 1944. The effect of hypoxemia on secondary C-hypovitaminosis. Amer. Rev. Sov. Med. 1:314. Brunquist, E. H., E. J. Schneller and A. S. Loeven- hart. 1924. The effects of anoxemia on nitrogen metabolism. J. Biol. Chem. 62:93. Bullard, R. W. and G. E. Funkhouser. 1960. Cited in: Van Liere, E. J. and J. C. Stickney. 1968. Hypoxia. Chicago: Univ. Chicago Press. Bullard, R. W. and J. L. Snyder. 1961. Hypoxic alteration of righting ability and pain threshold in two mammalian species. Proc. Soc. Exp. Biol. Med. 106:341. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 263 Burker, K., R. Ederle and F. Kircher. 1913. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Burton, R. R., R. Sahara and A. H. Smith. 1971. The hematology of domestic fowl native to high altitude. Environ. Physiol. 1:155. Burton, R. R. and A. H. Smith. 1969. Induction of cardiac hypertrophy and polycythemia in the developing chick at high altitude. Fed. Proc. 28:1170. Calder, R. M. 1948. Effect of nicotinic acid on anoxia in rats. Proc. Soc. Exp. Biol. Med. 68:642. Campbell, J. A. 1935. Further evidence that mammals cannot acclimatize to 10 p.c. oxygen or 20,000 feet altitude. Brit. J. Exp. Path. 16:39. Cardozo, A. 1970. El Altiplano de Bolivia y la Cria de Ovejas. Cochabamba, Bolivia: Univ. Mayor de San Simon. Carlson, A. J. 1916. The Control of Hunger in Health and Disease. Chicago: Univ. Chicago Press. Carson, R. P., W. 0. Evans, J. L. Shields and J. P. Hannon. 1969. Symptomatology, pathophysiology and treatment of acute mountain sickness. Fed. Proc. 28:1085. Cattell, M. and H. Civin. 1938. The influence of asphyxia and other factors on the serum potassium of cats. J. Biol. Chem. 126:633. Chandra, S. V. and S. K. Tandon. 1973. Enhanced Mg toxicity in iron-deficient rats. Environ. Physiol. Biochem. 3:230. Chardon, G., G. Neverre and G. Jeannoel. 1949. Modifications de la sécrétion biliaire sous l'influence du deficit en oxygene. Soc. Biol. C. R. (Paris) 143:697. Charipper, H. A., E. D. Goldsmith and A. S. Gordon. 1944. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 264 Charipper, H. A., E. D. Goldsmith and A. S. Gordon. 1945. Vitamin deficiency and overdosage and the resistance of rats to lowered barometric pressures. Amer. J. Physiol. 145:130. Childs, S. B., Jr., H. Hamlin and Y. Henderson. 1935. Possible value of inhalation of carbon dioxide in climbing great altitudes. Nature 135:457. Chinn, K. S. K. and J. P. Hannon. 1969. Efficiency of food utilization at high altitude. Fed. Proc. 28:944. Chiodi, H. 1957. Respiratory adaptations to chronic high altitude hypoxia. J. Appl. Physiol. 10:81. Chiodi, H. P. and R. Bass. 1969. Hypoxic fatty liver degeneration in suckling rats. Fed. Proc. 28:1080. Christensen, W. R. and M. Clinton, Jr. 1947. Effect of cytochrome C therapy on altitude tolerance of normal rats. Proc. Soc. Exp. Biol. Med. 66:360. Cohnheim, O. 1913. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Collins, J. D. and B. T. Farrell. 1969. Changes in number and quality of erythrocytes in horses transported to high altitudes. Irish Vet. J. 23:42. Committee on Biological Handbooks. 1971. Blood and Other Body Fluids. Altman, P. L. and D. S. Dittmer, Eds. Washington, D.C.: Federation of American Societies for Experimental Biology. Consolazio, C. F. 1963. The energy requirements of men living under extreme environmental conditions. World Rev. Nutr. Diet. 4:53. Consolazio, C. F., L. O. Matoush, H. L. Johnson, H. J. Krzywicki, T. A. Daws and G. J. Isaac. 1969. Effects of high-carbohydrate diets on per- formance and clinical symptomatology after rapid ascent to high altitude. Fed. Proc. 28:937. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 265 Cordier, D. and J. Chanel. 1950. Influence of the carbon dioxide tension of the inspired air on the rate of gastric passage in normal and anoxic rats. Soc. Biol. C. R. (Paris) 144:535. Craven, C. W. 1951. Oxygen consumption of rats during partial inanition. Amer. J. Physiol. 167:617. Crisler, G., E. J. Van Liere and W. T. Booher. 1932.. The effect of anoxemia on the digestive movements of the stomach. Amer. J. Physiol. 102:629. Cullumbine, H. 1952. Changes in composition of tissues of mice after exposure to low pressure. Amer. J. Physiol. 169:515. Dallwig, H. C., A. C. Kolls and A. S. Loevenhart. 1915. The mechanism adapting the oxygen capacity of the blood to the requirements of the tissues. Amer. J. Physiol. 39:77. Darrow, D. C. and E. L. Sarason. 1944. Some effects of low atmospheric pressure on rats. J. Clin. Invest. 23:11. Davidovic, J. and I. Wesley. 1959. Tolerance of cooled animals to acute hypoxia during rewarming. Amer. J. Physiol. 197:1357. Davies, H. W., J. B. S. Haldane and E. L. Kennaway. 1920. Experiments on the regulation of the blood's alkalinity. J. Physiol. 54:32. Davis, B. D. and B. F. Jones. 1943. Effects of estrogens on altitude tolerance. Endocrinology 33:23. Davis, T. R. A. 1964. The influence of climate on nutritional requirements. Amer. J. Public Health. 54:2051. De Haan, R. L. and J. Field. 1959. Anoxic endurance of cardiac and respiratory function in the adult and infant rat. Amer. J. Physiol. 197:445. Dennis, J. and F. J. Mullin. 1938. Blood potassium changes as a result of partial asphyxia in dogs. Proc. Soc. Exp. Biol. Med. 38:560. Dill, D. B. 1938. Life, Heat and Altitude. Cam- bridge: Harvard University Press. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 266 Dill, D. B., O. O. Benson, Jr., W. H. Forbes and F. G. Hall. 1940. Benzedrine sulphate (ampheta- mine) and acute anoxia. I. Respiratory effects. J. Aviat. Med. 11:181. Dill, D. B., J. H. Talbott and W. V. Consolazio. 1937. Blood as a physicochemical system. XII. Man at high altitudes. J. Biol. Chem. 118:649. Dorrance, S. S., G. W. Thorn, M. Clinton, Jr., H. W. Edmonds and S. Farber. 1943. Effect of cobalt on work performance under conditions of anoxia. Amer. J. Physiol. 139:399. Drastich and Lejhanec. Cited in: Loewy, A. and E. Wittkower. 1937. The Pathology of High Altitude Climate. London: Oxford University Press. Dukes, H. H. 1970. Physiology of Domestic Animals. 8th Edition. M. J. Swenson, Ed. Ithaca: Com- stock Pub. Associates. Edelman, I. S. and J. Liebman. 1959. Anatomy of body water and electrolytes. Amer. J. Med. 27:256. Edwards, H. T. 1936. Lactic acid in rest and work at high altitude. Amer. J. Physiol. 116:367. Emerson, G. A. 1943. Drug prophylaxis against lethal effects of severe anoxia. VI. Neostigmine bromide and diphenylhydantoin. Proc. Soc. Exp. Biol. Med. 54:252. Emerson, G. A. and E. J. Van Liere. 1943. Drug prophylaxis against lethal effects of severe anoxia. V. Agents affecting the autonomic nervous system. J. Lab. Clin. Med. 28:700. Erslev, A. J. 1974. In vitro production of erythro- poietin by kidneys perfused with a serum-free solution. Blood. 44:77. Fazekas, J. F., F. A. D. Alexander and H. E. Himwich. 1941. Tolerance of the newborn to anoxia. Amer. J. Physiol. 134:281. Feigen, G. A. and P. R. Johnson. 1964. Blood volumes and heart weights in two strains of rats during adaptation to a natural altitude of 12,470 feet. In: The Physiological Effects of High Altitude. 1964. W. H. Weihe, Ed. New York: The MacMillan Co. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 267 Feldman, J., R. Cortell and S. Gellhorn. 1940. On the vago-insulin and sympathetico-adrenal system and their mutual relationship under con- ditions of central excitation induced by anoxia and convulsant drugs. Amer. J. Physiol. 131:281. Ferguson, F. P. and D. C. Smith. 1953. Effects of acute decompression stress upon plasma electro- lytes and renal function in dogs. Amer. J. Physiol. 173:503. Fitzgerald, M. P. 1913. The changes in the breath- ing and the blood at various high altitudes. Phil. Trans. Roy. Soc. London B. 203:351. Flores, M., M. T. Menchu and G. Arroyave. 1969. Ingesta da micronutrientes en las areas de Centro America y Panama. Arch. Latinamericanos de Nutricién. 19:265. Folk, G. E., Jr. 1966. Introduction to Environ- mental Physiology. Philadelphia: Lea & Febiger. Forbes, W. H. 1936. Blood sugar and glucose tolerance at high altitudes. Amer. J. Physiol. 116:309. Fowler, N. 0., R. Shabetai and J. C. Holmes. 1961. Adrenal medullary secretion during hypoxia, bleeding, and rapid intravenous infusion. Circulat. Res. 9:427. Freedman, A. M. and H. E. Himwich. 1948. Anoxic survival and diisopropyl fluorophosphate (DFP). Science. 108:41. Fridhandler, L. and J. H. Quastel. 1955. Absorption of amino acids from isolated surviving intestine. Arch. Biochem. 56:424. Fryers, G. R. 1952. Effect of decreased atmospheric pressure on blood volume of rats. Amer. J. Physiol. 171:459. Gellhorn, E. 1936. The effect of OZ-lack, variations in the COz-content of the inspired air, and hyperpnea on visual intensity discrimination. Amer. J. Physiol. 115:679. Gellhorn, E. 1937. Oxygen deficiency, carbon dioxide and temperature regulation. Amer. J. Physiol. 120:190. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 268 Gellhorn, E. and A. C. Packer. 1939. Influence of anoxia on glycogenolytic action of adrenalin. Proc. Soc. Exp. Biol. Med. 41:345. Giragossintz, G. and E. S. Sundstroem. 1937. Corti- coadrenal insufficiency in rats under reduced pressure. Proc. Soc. Exp. Biol. Med. 36:432. Gloster, J., D. Heath and P. Harris. 1972. The influence of diet on the effects of a reduced atmospheric pressure in the rat. Environ. Physiol. Biochem. 2:117. Gloster, J., D. Heath and P. Harris. 1972. Lipid composition of the heart and lungs of rats during exposure to a low atmospheric pressure. Environ. Physiol. Biochem. 2:125. Gloster, J., Y. Oertel, D. Heath, J. Arias-Stella and P. Harris. 1971. The lipid composition of the myocardium of animals indigenous to high and low altitudes. Environ. Physiol. 1:77. Glover, G. H. and I. E. Newsom. 1915. Brisket Disease. Bulletin 204. Ft. Collins: Colo. Agr. College. Glover, G. H. and I. E. Newsom. 1917. Brisket Disease. Bull. 229. Ft. Collins: Colo. Agr. College. Glover, G. H. and I. E. Newsom. 1918. Further studies on brisket disease. J. Agr. Res. 15:409. Goebel, F. and S. Marczewski. 1938. Acclimatization of the human organism to low atmospheric pressures. Acta Biol. Exp. (Warsaw) 12:87. Goldsmith, E. D., A. S. Gordon and H. A. Charipper. 1945. Estrogens, thiourea, thiouracil and the tolerance of rats to simulated high altitudes (low atmospheric pressures). Endocrinology. 36:364. Gordon, A. S. 1959. Hemopoietine. Physiol. Rev. 39:1. Gordon, A. S., E. D. Goldsmith and H. A. Charipper. 1944. Effects of thiouracil and 5,5-diphenyl hydantoinate (dilantin sodium) on resistance to lowered barometric pressures. Proc. Soc. Exp. Biol. Med. 56:202. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 269 Gordon, A. S., E. D. Goldsmith and H. A. Charipper. 1945. Effects of p—aminobenzoic acid and thioura- cil on thyroid function and resistance to low pressures. Endocrinology. 37:223. Gordon, A. S., F. J. Tornetta and H. A. Charipper. 1943. Effect of low atmospheric pressures on the reproductive system of the male rat. Proc. Soc. Exp. Biol. Med. 53:6. Govier, W. M. 1944. Rationale for use of vitamins in the therapy of shock and anoxia. J. Am. Med. Assoc. 126:749. Grant, W. C. and W. S. Root. 1952. Fundamental stimulus for erythrOpoiesis. Physiol. Rev. 32:449. Grawitz, E. 1895. Cited in: Hannon, J. P., K. S. Chinn and J. L. Shields. 1969. Effects of acute high-altitude exposure on body fluids. Fed. Proc. 28:1178. Gray, E. L. 1955. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Green, D. M., J. S. Butts and H. F. Mulholland. 1945. The relationship of anoxia susceptibility to diet. J. Aviat. Med. 16:311. Greig, M. E. and W. M. Govier. 1943. Studies on shock induced by hemorrhage. IV. The dephos- phorylation of cocarboxylase in tissues during shock and anoxia. J. Pharmacol. Exp. Ther. 79:169. Grice, H. C., T. Goodman, I. C. Munro, G. S. Wiberg and A. B. Morrison. 1969. Myocardial toxicity of cobalt in the rat. Ann. N.Y. Acad. Sci. 156:189. ‘ Gusman, S. M., D. M. Shteingart and K. M. Kharadze. 1946. Effect of flight on the vitamin metabolism of aviators. Chem. Abst. 40:2213. Hailman, H. F. 1944. The effect of vitamins of the B complex on the resistance of the organism to anoxia. Amer. J. Physiol. 141:176. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 270 Haldane, J. S., A. M. Kellas and E. L. Kennaway. 1919. ExPeriments on acclimatisation to reduced atmospheric pressure. J. Physiol. 53:181. Hale, H. B., G. Sayers, K. Sydnor, M. L. Sweat and D. D. Van Fossan. 1957. Blood adrenocortico- trophic hormone and plasma corticosteroids in men exposed to adverse environmental conditions. J. Clin. Invest. 36:1642. Halstead, W. C. 1945. Chronic intermittent anoxia and impairment of peripheral vision. Science. 101:615. Hannon, J. P., K. S. K. Chinn and J. L. Shields. 1969. Effects of acute high-altitude exposure on body fluids. Fed. Proc. 28:1178. Hanson, V. 1952. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Hartiala, K. J. V. 1951. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Hecht, H. H., H. Kuida, R. L. Lange, J. L. Thorne and A. M. Brown. 1962. Brisket Disease. II. Clinical features and Hemodynamic observations in altitude-dependent right heart failure of cattle. Amer. J. Med. 32:171. Hecht, H. H., R. L. Lange, W. H. Carnes, H. Kuida and J. T. Blake. 1959. Brisket Disease. I. General aspects of pulmonary hypertensive heart disease in cattle. Trans. Assoc. Amer. Physicians. 72:157. Hellebrandt, F. A., E. Brogdon and S. L. HOOpes. 1935. The effect of acute anoxemia on hunger, digestive contractions and the secretion of hydrochloric acid in man. Amer. J. Physiol. 112:451. Hershgold, E. J. and M. B. Riley. 1959. Diet induced variations in tolerance to altitude hypoxia in the mouse. Proc. Soc. Exp. Biol. Med. 100:831. Hiestand, W. A. and H. R. Miller. 1944. Further observations on factors influencing hypoxic resistance of mice. Amer. J. Physiol. 142:310. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 271 Hill, J. R. 1959. The oxygen consumption of new- born and adult mammals. Its dependence on the oxygen tension in the inspired air and on the environmental temperature. J. Physiol. 149:346. Hilton, J. G. and R. A. Woodbury. 1951. Influence of low oxygen tension and lowered glucose levels on uterine activity. Fed. Proc. 10:309. Hingston, R. W. G. Cited in: Barcroft, J. 1925. The Respiratory Function of the Blood, Part I. Lessons from High Altitudes. Cambridge: Cam- bridge Univ. Press. Hoff, E. C. and C. Yahn. 1944. The effect of sodium 5,5-diphenyl hydantoinate (dilantin sodium) upon the tolerance of rats and mice to decompres- sion. Amer. J. Physiol. 141:7. Houston, C. S. and R. L. Riley. 1947. ReSpiratory and circulatory changes during acclimatization to high altitude. Amer. J. Physiol. 149:565. Hove, E. L., K. Hickman and P. L. Harris. 1945. The effect of tocopherol and of fat on the resistance of rats to anoxic anoxia. Arch. Biochem. 8:395. Huckabee, W. E. 1958. Relationships of pyruvate and lactate during anaerobic metabolism. I. Effects of infusion of pyruvate or glucose and of hyperventilation. J. Clin. Invest. 37:244. Huckabee, W. E. 1958. Relationships of pyruvate and lactate during anaerobic metabolism. III. Effect of breathing low-oxygen gases. J. Clin. Invest. 37:264. Hughes, A. M. 1944. Resistance to the anoxia of high altitude afforded by thiouracil. Fed. Proc. 3:21. Hurtado, A. 1932. Studies at high altitude. Respiratory adaptation in the Indian natives of the Peruvian Andes. Amer. J. Phys. Anthropology. 17:137. Hurtado, A. 1932. Studies at high altitude. Blood observations on the Indian natives of the Peruvian Andes. Amer. J. Physiol. 100:487. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 272 Hurtado, A. 1964. Acclimatization to High Alti- tudes. In: The Physiological Effects of High Altitude. Weihe, W. H., Ed. Symposium held at Interlaken, Sept. 18-22, 1962. New York: The MacMillan Co. Hurtado, A. 1964. In: Handbook of Physiology. Adaptation to the Environment. Sect. 4. Washington, D.C.: Am. Physiol. Soc. Hurtado, A., C. Merino and E. Delgado. 1945. Influence of anoxemia on the hemopoietic activity. Arch. Internal Med. 75:284. Ilk, S. G., J. J. Seguin, B. Balraj and J. A. F. Stevenson. 1961. A criterion to assess the effect of various factors on altitude tolerance. Fed. Proc. 20:211. Informe. 1970-72. Instituto Nacional de Investi- gaciones Agropecuarias. Quito, Ecuador. Instituto Nacional de Investigaciones AgrOpe- cuarias. Quito, Ecuador. Unpublished Information. Janoski, A. H., B. K. Whitten, J. L. Shields and J. P. Hannon. 1969. Electrolyte patterns and regulation in man during acute exposure to high altitude. Fed. Proc. 28:1185. Jarcho, S. 1958. Mountain sickness as described by Fray Joseph De Acosta, 1589. Amer. J. Cardiology. 2:246. Jordan, J. P., J. B. Simmons, 11., D. V. Lassiter, Y. Deshpande and D. J. Dierschke. 1969. Metabolic effects of nitrogen and neon as diluent environmental gases. In: Depressed Metabolism, Musacchia, x. J. and J. F. Saunders, Eds. New York: Amer. Elsevier Publishing Co. Kaufman, P., J. Hollo, J. Rosenthal, J. Stone, R. D. Beck and V. Fink. 1950. The effect of 10 per cent and 100 per cent oxygen inhalation on certain liver-function tests. New Eng. J. Med. 242:90. Kerwin, A. J. 1944. Observations on the heart size of natives living at high altitudes. Amer. Heart J. 28:69. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 273 Kessler, M., H. Hailman and E. Gellhorn. 1943. Studies on the effect of anoxic anoxia on the central nervous system. Amer. J. Physiol. 140:291. Keyes, G. H. and V. C. Kelley. 1949. Glucose tolerance of dogs as altered by atmospheric decompression. Amer. J. Physiol. 158:358. Keys, A., J. P. Stapp and A. Violante. 1943. Responses in size, output and efficiency of the human heart to acute alteration in the compo- sition of inspired air. Amer. J. Physiol. 138:763. Klain, G. J. and J. P. Hannon. 1970. High altitude and protein metabolism in the rat. Proc. Soc. Exp. Biol. Med. 134:1000. Kline, R. F. 1947. Increased tolerance to severe anoxia on carbon dioxide administration. Amer. J. Physiol. 151:538. Kline, R. F. 1947. Effects of severe anoxia and their amelioration. Fed. Proc. 6:143. Kottke, F. J., J. S. Phalen, C. B. Taylor, M. B. Visscher and G. T. Evans. 1948. Effect of hypoxia upon temperature regulation of mice, dogs and man. Amer. J. Physiol. 153:10. Krzywicki, H. J., C. F. Consolazio, L. O. Matoush, H. L. Johnson and R. A. Barnhart. 1969. Body composition changes during exposure to altitude. Fed. Proc. 28:1190. Lahiri, S. 1971. Genetic aspects of the blunted chemoreflex ventilatory response to hypoxia in high altitude adaptation. In: High Altitude Physiology: Cardiac and Respiratory Aspects. 1971. R. Porter and J. Knight, Eds. London: Churchill Livingstone. Laugier, H. and C. P. Leblond. 1943. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Lawless, J. J. and E. J. Van Liere. 1947. The effect of various degrees of anoxic anoxia on water distribution in the body. Amer. J. Physiol. 149:103. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 274 Leblond, C. P. 1944. Increased resistance to anoxia after thyroidectomy and after treatment with thiourea. Proc. Soc. Exp. Biol. Med. 55:114. Leblond, C. P., J. Gross and H. Laugier. 1943. Effect of fasting on resistance to anoxia. J. Aviat. Med. 14:262. Leipert, T. and E. Kellersmann. 1942. Carbohydrate metabolism in anoxia. I. Hyperglycemic reaction. Pyruvic acid and phosphate metabolism. z. Physiol. Chem. 276:214. Lenfant, C., J. Torrance, E. English, C. A. Finch, C. Reynafarje, J. Ramos and J. Faura. 1968. Effect of altitude on oxygen binding by hemo- globin and on organic phosphate levels. J. Clin. Invest. 47:2652. Li, C. H. and V. V. Herring. 1945. Effect of adrenocorticotropic hormone on the survival of normal rats during anoxia. Amer. J. Physiol. 143:548. Lintzel, W. 1931. Cited in: ‘Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Loaysa, 0., E. Flores, E. Ramirez, J. Hidalgo and G. Carbo. 1971. Respuesta hematologica al cambio de altitud en pacientes con anemia anquilosto- miasica. Revista Ecuatoriana Med. Ciencias Biolég. 9:23. Loehning, R. W., V. Zapata-Ortiz, F. W. Hughes and A. L. Tatum. 1952. Effects of chronic ingestion of cocaine on tolerance to low oxygen. J. Pharm. Exp. Ther. 106:404. Loewy, A. and E. Wittkower. 1933. Further studies on the physiology of high altitudes. Arch. Geo. Physiol. 233:622. Loewy, A. and E. Wittkower. 1937. The Pathology of High Altitude Climate. London: Oxford Univ. Press. Luft, U. C. In: Aerospace Medicine. H. G. Arm- strong, Ed. 1961. Baltimore: Williams and Wilkins Co. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 275 Luft, U. C., D. Cardus, T. P. K. Lim, E. C. Anderson and J. L. Howarth. 1963. Physical performance in relation to body size and com— position. Ann. N.Y. Acad. Sci. 110:795. McDowell, L. R., J. H. Conrad, J. E. Thomas and L. E. Harris. 1974. Latin American Tables of Feed Composition. Gainesville: Univ. Florida. McFarland, R. A. 1937. Psycho-physiological studies at high altitude in the Andes. II. Sensory and motor responses during acclimati- zation. J. Comp. Psychol. 23:227. McFarland, R. A. 1937. Psycho-physiological studies at high altitude in the Andes. J. Comp. Psychol. 24:189. McFarland, R. A. and M. H. Halperin. 1940. The relation between foveal visual acuity and illumination under reduced oxygen tension. J. Gen. Physiol. 23:613. MacLachlan, P. L. 1939. The effects on blood lipids of short exposure to low atmospheric pressure. J. Biol. Chem. 129:465. MacLachlan, P. L. 1946. Effect of anoxic anoxia on gastric emptying time of rats fed corn oil. Proc. Soc. Exp. Biol. Med. 63:147. MacLachlan, P. L., C. K. Sleeth and J. Gover. 1947. Effect of anoxic anoxia on bile secretion in the rat. Proc. Soc. Exp. Biol. Med. 66:275. MacLachlan, P. L. and C. W. Thacker. 1945. The effect of anoxia on fat absorption in rats. Amer. J. Physiol. 143:391. McQuarrie, I., M. R. Ziegler and L. J. Hay. 1942. ReSponse of the vago-insulin system to anoxia as demonstrated in adrenalectomized dogs. Endocrinology 30:898. McQuarrie, I., M. R. Ziegler, W. E. Stone, 0. H. Wangensteen and C. Dennis. 1939. Mechanism of insulin convulsions. III. Effects of varying partial pressures of atmospheric gases after adrenalectomy. Proc. Soc. Exp. Biol. Med. 42:513. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194 . 195. 196. 276 Manual of Analytical Methods. 1972. Atomic Absorption Spectrophotometry. Perkin-Elmer Corp., Norwalk, Conn. Margaria, R. and L. Faraglia. 1940. Changes in resistance to anoxia provoked by variations in the acid-base balance of the blood. Boll. Soc. Ital. Biol. Sper. 15:1096. Mazess, R. B. 1969. Exercise performance at high altitude in Peru. Fed. Proc. 28:1301. Merino, C. F. 1950. Studies on blood formation and destruction in the polycythemia of high altitude. Blood 5:1. Milledge, J. S. 1971. In: High Altitude Phy- siology: Cardiac and Respiratory Aspects. 1971. R. Porter and J. Knight, Eds. London: Churchill Livingstone. Miller, J. A. 1949. Factors in neonatal resistance to anoxia. I. Temperature and survival of new- born guinea pigs under anoxia. Science 110:113. Miller, J. A., Jr. and F. S. Miller. 1961. Hypo- thermic protection against asphyxia in newborn puppies. Fed. Proc. 20:214. Miller, J. A., Jr., F. S. Miller and C. B. Farrar. 1951. Effects of temperature upon resistance of guinea pigs to anoxia. Fed. Proc. 10:92. Miller, M. E., D. Howard, F. Stohlman, Jr. and P. Flanagan. 1974. Mechanism of erythrOpoietin production by cobaltous chloride. Blood 44:339. Monge C., C. 1954. Man, Climate and Changes of Altitude. Meteor. Monographs 2(8):50. Monge C., C. 1948. Acclimatization in the Andes. Historical Confirmations of Climatic Agression in the Development of Andean Man. Translated by D. F. Brown. Baltimore: The Johns Hopkins Press. Monge, C., R. Lozano, C. Marchena, J. Whittemburg and C. Torres. 1969. Kidney function in the high-altitude native. Fed. Proc. 28:1199. Monge M., C. and C. Monge C. 1966. High Altitude Diseases. Springfield, 111.: Charles C. Thomas. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 277 Monge M., C. and C. Monge C. 1968. Adaptation to High Altitude. In: Adaptation of Domestic Animals. E. S. E. Hafez, Ed. Philadelphia: Lea and Febiger. Nasmith, G. G. and F. C. Harrison. 1910. Changes induced in the blood of rabbits by living in an atmosphere of water gas. J. Exp. Med. 12:282. National Research Council, Committee on Animal Nutrition. 1971. Nutrient Requirements of Dairy Cattle. Publication No. 1916. National Academy of Sciences-National Research Council, Washington, D.C. Nelson, M. L. 1971. Thyroid function in immature rats developing at high altitude. Environ. Psysiol. 1:96. Northrup, D. W. and E. J. Van Liere. 1939. Intestinal secretion during anoxia. Proc. Soc. Exp. Biol. Med. 42:162. Northrup, D. W. and E. J. Van Liere. 1941. The effect of anoxia on the absorption of glucose and of glycine from the small intestine. Amer. J. Physiol. 134:288. Oleas A., T. B. 1974. Analisis de Carbohidratos y Fibras en Pastos de la Estacion "Santa Cata- lina." Tesis: Ingeniero Agronomo. Quito, Ecuador: Universidad Central. Pace, N. 1974. Respiration at high altitude. Fed. Proc. 33:2126. Phillips, N. E., P. A. Saxon and F. H. Quimby. 1947. Humidity and tolerance to low barometric pressure. Science 106:67. Phillips, N. E., P. A. Saxon and F. H. Quimby. 1950. Effect of humidity and temperature on the survival of albino mice exposed to low atmOSpheric pressure. Amer. J. Physiol. 161:307. Phillips, R. W., K. L. Knox, W. A. House and H. N. Jordan. 1969. Metabolic responses in sheep chronically exposed to 6,200 m. simulated altitude. Fed Proc. 28:974. .1" I iii“. mart .‘a I. '- 208. 209. 210. 211. 212. 213. 214. 215. 216. 217. 218. 278 Pickett, A. D. and E. J. Van Liere. 1939. The effect of anoxia on gastric secretion from Pavlov and Heidenhain pouch dogs. Amer. J. Physiol. 127:637. Picon-Reategui, E., G. R. Fryers, N. I. Berlin and J. H. Lawrence. .1953. Effect of reducing the atmospheric pressure on body water content of rats. Amer. J. Physiol. 172:33. Pincus, G. and H. Hoagland. 1943. Steroid excretion and the stress of flying. J. Aviat. Med. 14:173. Pugh, L. G. C. and M. P. Ward. 1956. Some effects of high altitude on man. Lancet 271:1115. Quimby, F. H., N. E. Phillips, B. B. Cary and R. Morgan. 1948. Effect of humidity on the change in body temperature of the albino rat during exposure to low atmospheric pressures. Amer. J. Physiol. 155:462. Rahn, H. and A. B. Otis. 1947. Alveolar air during simulated flights to high altitudes. Amer. J. Physiol. 150:202. Rasmussen, P. 1969. The relationship of nutrition to fatty degeneration of the myocardium and kidney. Ann. N.Y. Acad. Sci. 156:130. Reeves, J. T., R. F. Grover and S. G. Blount, Jr. 1960. Altitude as a stress to the pulmonary circulation of steers. Clin. Res. 8:138. Reynafarje, B. 1962. Myoglobin content and enzymatic activity of muscle and altitude adaptation. J. Appl. Physiol. 17:301. Reynolds, 0. E. and N. E. Phillips. 1947. Adap- tation of the albino rat to discontinuous chronic exposure to altitude anoxia. Amer. J. Physiol. 151:147. Riesen, A. H., T. N. Tahmisian and C. G. Mackenzie. 1946. Prolongation of consciousness in anoxia of high altitude by glucose. Proc. Soc. Exp. Biol. Med. 63:250. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 279 Robillard, E. and M. Gagnon. 1953. Resistance to acute anoxia of the rat exposed to relatively low environmental temperature. Rev. Canad. Biol. 12:411. Rotta, A. 1947. Physiologic condition of the heart in the natives of high altitudes. Amer. Heart J. 33:669. Rotter, W. 1941. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Royce, P. C. and G. Sayers. 1960. Purification of hypothalmic corticotropin releasing factor. Proc. Soc. Exp. Biol. Med. 103:447. Ruiz, A. V., G. E. Bisgard, and J. A. Will. 1973. Hemodynamic responses to hypoxia and hyperoxia in calves at sea level and altitude. Pflfigers Arch. 344:275. Samson, F. E., Jr., W. M. Balfour and N. Dahl. 1958. Cerebral ATP concentration during anoxia in rats. Fed. Proc. 17:140. Schaffeler, K. and M. Flury. 1948. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Schmensky, K. Cited in: A. Loewy and E. Wittkower. 1937. The Pathology of High Altitude Climate. London: Oxford University Press. Schmidt, J. P. 1969. Resistance to infectious disease versus exposure to hypobaric pressure and hypoxic, normoxic or hyperoxic atmospheres. Fed. Proc. 28:1099. Schnedorf, J. G. and T. G. Orr. 1941. The effect of anoxemia and oxygen therapy upon the flow of bile and urine in the nembutalized dog. II. Its possible relationship to the hepatorenal syndrome. Amer. J. Dig. Dis. 8:356. Schubert, G. 1937. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Lil 230. 231. 232. 233. 234. 235. 236. 237. 238. 239. 240. 241. 280 Selle, W. A. 1944. Influence of glucose on the gasping pattern of young animals subjected to acute anoxia. Amer. J. Physiol. 141:297. Shocket, E., M. M. Jackson and H. C. Dyme. 1953. The effect of moderate altitude upon human gastric emptying time. J. Aviat. Med. 24:113. Sleeth, C. K. and E. J. Van Liere. 1937. Effect of anoxemia on the impermeability of the stomach to water. Proc. Soc. Exp. Biol. Med. 36:571. Smith, A. H., R. R. Burton and E. L. Besch. 1969. DevelOpment of the chick embryo at high altitude. Fed. Proc. 28:1092. Smith, D. C., R. H. Oster and J. E. P. Toman. 1944. The effect of thiamine deficiency and of reduced food intake on resistance to low oxygen tension in the cat. Amer. J. Physiol. 140:603. Smith, H. P., A. E. Belt, H. R. Arnold and E. B. Carrier. 1925. Blood volume changes at high altitude. Amer. J. Physiol. 71:395. Smith, M. I. 1918. The action of the autonomic drugs on the surviving stomach. Amer. J. Physiol. 46:232. Sobel, H., M. Sideman and R. Arce. 1960. Effect of cortisone on survival of morphine treated guinea pigs under decompression hypoxia. Proc. Soc. Exp. Biol. Med. 104:31. Stickney, J. C. 1946. Effect of anoxic anoxia on body weight loss in rats. Proc. Soc. Exp. Biol. Med. 63:210. Stickney, J. C., D. W. Northrup and E. J. Van Liere. 1948. Blood sugar and dextrose tolerance during anoxia in the dog. Amer. J. Physiol. 154:423. Stickney, J. C., D. W. Northrup and E. J. Van Liere. 1950. Studies on effect of anoxic anoxia on goat blood sugar. Fed. Proc. 9:122. Stickney, J. C., D. W. Northrup and E. J. Van Liere. 1951. Blood sugar and hemoglobin responses to anoxia in sheep and the effect of acclimatization. Amer. J. Physiol. 167:559. f F mam )- I'll!“ IIII' 1"! 242. 243. 244. 245. 246. 247. 248. 249. 250. 251. 252. 281 Stickney, J. C. and E. J. Van Liere. 1953. Acclimatization to low oxygen tension. Physiol. Rev. 33:13. Strughold, H. 1930. A cinematographic study of systolic and diastolic heart size with special reference to the effects of anoxemia. Amer. J. Physiol. 94:641. Sundstroem, E. S. and W. R. Bloor. 1920. The physiological effects of short exposure to low pressure. J. Biol. Chem. 45:153. Surks, M. I., K. S. K. Chinn and L. O. Matoush. 1966. Alterations in body composition in man after acute exposure to high altitude. J. Appl. Physiol. 21:1741. Tanturi, C. A. and A. C. Ivy. 1938. A study of the effect of vascular changes in the liver and the excitation of its nerve supply on the for- mation of bile. Amer. J. Physiol. 121:61. Telford, I. R., O. B. Wiswell and E. L. Smith. 1954. TocoPheral prophylaxis in multiple exposure to hypoxia. Proc. Soc. Exp. Biol. Med. 87:162. Tengerdy, R. P., R. H. Heinzerling and C. F. Nockels. 1972. Effect of vitamin E on the immune response of hypoxic and normal chickens. Infection & Immunity 5:987. Tepperman, J., H. M. Tepperman, B. W. Patton and L. F. Nims. 1947. Effects of low barometric pressure on the chemical composition of the adrenal glands and blood of rats. Endocrinology 41:356. Tiku, J. L. 1970. High altitude sickness in Kashmir Valley at Leh. Indian Vet. J. 47:88. Tilley, J. M. A. and R. A. Terry. 1963. A two- stage technique for the in vitro digestion of forage crOps. J. Brit. Grassland Soc. 18:104. Timiras, P. S. 1964. Comparison of growth and development of the rat at high altitude and at sea level. In: The Physiological Effects of High Altitude. 1964. W. H. Weihe, Ed. New York: The MacMillan Co. 253. 254. 255. 256. 257. 258. 259. 260. 261. 262. 263. 264. 265. 282 Timiras, P. S. 1965. High altitude studies. In: Methods of Animal Experimentation. 1965. W. I. Gay, Ed. New York: Academic Press. Underwood, E. J. 1962. Trace Elements in Human and Animal Nutrition. New York: Academic Press. Underwood, E. J. 1971. Trace Elements in Human and Animal Nutrition. New York: Academic Press. Vacca, C. and E. Boeri. 1953. Cited in: Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. Chicago Press. Valdivia, E. 1957. Right ventricular hypertrophy in guinea pigs exposed to simulated high altitude. Circulat. Res. 5:612. Van Liere, E. J. 1936. Effect of anoxemia on the emptying time of the human stomach. Influence of high altitudes. AMA Arch. Intern. Med. 58:130. Van Liere, E. J. 1936. The effect of prolonged anoxemia on the heart and spleen in the mammal. Amer. J. Physiol. 116:290. Van Liere, E. J., W. V. Crabtree, D. W. Northrup and J. C. Stickney. 1948. Effect of anoxic anoxia on propulsive motility of the small intestine. Proc. Soc. Exp. Biol. Med. 67:331. Van Liere, E. J. and G. Crisler. 1930. The effect of anoxemia on hunger contractions. Amer. J. Physiol. 93:267. Van Liere, E. J., G. Crisler and D. Robinson. 1933. Effect of anoxemia on the emptying time of the stomach. AMA Arch. Intern. Med. 51:796. Van Liere, E. J., H. S. Fang and D. W. Northrup. 1954. Resistance to hypoxia produced by poly- cythemia in rats. Amer. J. Physiol. 178:503. Van Liere, E. J., D. H. Lough and C. K. Sleeth. 1936. The effect of ephedrine on the emptying time of the human stomach. JAMA 106:535. Van Liere, E. J., G. B. McCarty and J. G. Matthews. 1952. Effect of hypoxia and anemic anoxia on uterus. Amer. J. Physiol. 171:245. 266. 267. 268. 269. 270. 271. 272. 273. 274. 275. 276. A‘i—HJ'I 283 1.. Van Liere, E. J., D. W. Northrup, J. C. Stickney and G. A. Emerson. 1943. The effect of anoxia on peristalsis of the small and large intestine. Amer. J. Physiol. 140:119. Van Liere, E. J. and C. K. Sleeth. 1936. Absorption of sodium chloride from the small intestine at various degrees of anoxemia. Amer. J. Physiol. 117:309. Van Liere, E. J., C. K. Sleeth and D. Northrup. 1936. The effect of acute hemorrhage on the emptying time of the stomach. Amer. J. Physiol. 117:226. Van Liere, E. J. and J. C. Stickney. 1963. Hypoxia. Chicago: Univ. of Chicago Press. Van Liere, E. J. and P. E. Vaughan. 1940. The influence of anoxia on the absorption of sodium chloride and sodium sulphate from the small intestine. Amer. J. Physiol. 129:618. Van Middlesworth, L. and M. M. Berry. 1951. Iodide metabolism during anoxia, nephrectomy, trauma, avitaminosis and starvation in the rat. Amer. J. Physiol. 167:576. Vaughan, D. A., J. L. Steele and P. R. Korty. 1969. Metabolic effects of feeding aspirin to rats at simulated altitude. Fed. Proc. 28:1110. Viault, E. 1891. Sur la quantité d'oxygéne contenue dans 1e sang des animaux des hauts plateaux de l'Amerique du Sud. C.R. Acad. Sci (Paris) 112:295. Von Muralt, A. Where are we? A short review of high altitude physiology. In: The Physiological Effects of High Altitude. 1964. W. H. Weihe, Ed. New York: The MacMillan Co. Weihe, W. H. 1964. Some examples of endocrine and metabolic functions in rats during acclimati- zation to high altitude. In: The Physiological Effects of High Altitude. 1964. New York: The MacMillan Co. Weiser, O. L., N. J. Peoples, A. H. Tull and W. C. Morse. 1969. Effect of altitude on the micro- biota of man. Fed. Proc. 28:1107. 277. 278. 279. 280. 281. 282. 284 Wezler, K. and E. Frank. 1948. Cited in: Hypoxia. Van Liere, E. J. and J. C. Stickney. 1963. Chicago: Univ. Chicago Press. Whitten, B. K. and A. H. Janoski. 1969. Effects of high altitude and diet on lipid components of human serum. Fed. Proc. 28:983. Wilder, R. L. and S. W. Schultz. 1931. The action of atropine and adrenaline on gastric tonus and hypermotility induced by insulin hypoglycemia. Amer. J. PhysiOl. 96:54. Wilson, T. H. and G. Wiseman. 1954. The use of sacs of everted small intestine for the study of the transferrance of substances from the mucosal to the serosal surface. J. Physiol. 123:116. Zarrow, M. X., W. A. Hiestand, F. W. Stemler and J. E. Wiebers. 1951. Comparison of effects of experimental hyperthyroidism and hypothyroidism on resistance to anoxia in rats and mice. Amer. J. Physiol. 167:171. Zwemer, R. L. and F. H. Pike. 1938. Effect of nerve-excitation on potassium in body fluids. Ann. N.Y. Acad. Sci. 37:257. 9 111111 101 3 1111 64 Q a l [1 “1711111 3129 111m 1 1177 391 ‘ B IES 11 1