ACID-BASE BALANCE DURING POLYPNEA AND PANTING IN THE UNANESTHETIZED CAT I Thesis for the Degree of Ph. D. _ MBCHIGAN STATE UNIVERSITY ' MARY LAURENCE MORGAN 1972 This is to certify that the thesis entitled ACID-BASE BALANCE DURING POLYPNEA AND PANTING IN THE UNANESTHETIZED CAT presented by Mary Laurence Morgan has been accepted towards fulfillment of the requirements for Mdegree in thgiology 923”» BMW Major professor Date November 2; 1972 0-169 IIII LIBRAR Y L Michigan State University \ 2" ~.... BINDING BY ‘- HUAB 8. WW 100K BINDERY INC. LIBRARY BIN DERS SMIEPflIY Illrunznn Ill .1 u———‘ _ ACID-8A5 Unanestheti planted thermoco ad a cannula in albient temperat alues of rectal azd respiratory firming a 30-mim It the beginning Here analyzed f: Concentration w. the Henderson-H. Steady-Sta tures rose line E'J’Pothalamic te: Mature at all the relationshi lbflaminal tempe iEncephalic: te ”Mothermic ex ABSTRACT ACID-BASE BALANCE DURING POLYPNEA AND PANTING IN THE UNANESTHETIZED CAT BY Mary Laurence Morgan Unanesthetized cats, each equipped with chronically im- planted thermocouple guide tubes in the anterior hypothalamus and a cannula in the left carotid artery, were exposed to ambient temperatures between 32 and 42°C. Steady-state values of rectal, hypothalamic, and seven skin temperatures, and reSpiratory frequency, were recorded at 5-minute intervals during a 30-minute period. Samples of arterial blood, drawn at the beginning and end of the 30-minute measurement period, were analyzed for pH, PC02' and P02. Plasma bicarbonate concentration was calculated from pH and PCO2 values using the Henderson-Hasselbalch equation. Steady-state levels of rectal and average skin tempera- tures rose linearly with increasing ambient temperature. Hypothalamic temperature was linearly related to rectal tem— perature at all respiratory frequencies, but the slope of ‘Uhe relationship was altered by panting, so that a change in abdominal temperature was accompanied by a smaller change in diencephalic temperature after panting began than during 4. normothermic exposures . P de ace 2 respiratory i was steeper a blood was no‘ 0.1 unit as 1 L'A ‘ ~ltal‘bonate ' 3 ‘tv 2 " Values c ‘requenCy' M u 1 Pnase Mary Laurence Morgan PaCO declined curvilinearly from 43 to 28 mm Hg as 2 :respiratory frequency rose from 18 to 205/min. The decrease was steeper at low respiratory frequencies. pH of arterial blood was not dependent on respiratory frequency, but rose 0.1 unit as Paco was reduced from 43 to 28 mm Hg. Plasma 2 bicarbonate concentration was a direct linear function of Pacozo Pa0 rose from 90 to 120 mm Hg as respiratory frequency 2 increased from 20 to 70/min. In resting cats, PaO remained 2 at approximately 120 mm Hg as respiratory frequency rose to 250/min. In exercising animals, Pa02 was maintained at low- er values, compared to resting cats with the same respiratory frequency, when frequency was greater than 70/min. "Phase II" breathing, that is, the slow, deep respira- tory pattern characteristic of cattle, sheep, and dogs during very severe heat stress, was not observed in this study. These data are interpreted to indicate that unanesthe- tized cats exposed to heat stress hyperventilate during pant- ing, but successfully avoid alkalosis. Reduction of plasma bicarbonate concentration is believed to contribute to the retention of normal blood pH in the face of hypocapnia. The oxygen tension of arterial blood in unanesthetized, heat- stressed cats is determined by the thermally driven hyper- ventilation and the activity level of the animal. ACID-B in ACID-BASE BALANCE DURING POLYPNEA AND PANTING IN THE UNANESTHETIZED CAT BY Mary Laurence Morgan A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Physiology 1972 The autho: "s" sheen Ce: gOOO lectual leader h. A I‘D be u 3.621 R. H01 5::5 encourage: ACKNOWLEDGEMENTS The author is indebted to Dr. Thomas Adams for his patience, good humor, and insight as well as for his intel- lectual leadership and professional guidance; and to Kenneth R. Holmes and William S. Hunter for their assistance and encouragement. ii LIST OF TABLES . LIST OF FIGURES Why-w ..\...ouCCTION . . ‘W'. L Definiti 2.Pnylogen panting 3.Control 4.Re5pirat cooling - Effect 0 . Previous Summary '- ‘ lfirll‘N“. ..... if- _| «MIT OF THE he -~-HC:s . . 1' Animals L construe ' Urgery Care of 'EqUipmen MEasurem 8. Xfierime ° a Culat 9' Analysis ‘n A W \1 an» o D TABLE OF CONTENTS Page LIST OF TABLES O O O O O O O O O O O O O O O O O O 0 O O V LIST OF FIGURES . . . . . . . . . . . . . . . . . . . . vi INTRODUCTION. . . . . . . . . . . . . . . . . . . . . . 1 REVIEW OF THE LITERATURE. . . . . . . . . . . . . . . . 3 1. Definition of terms . . . . . . . . . . . . . . 3 2. Phylogenetic distribution of polypnea and panting . . . . . . . . . . . . . . . . . . . . 4 3. Control of panting. . . . . . . . . . . . . 5 4. Respiratory pattern and site of evaporative cooling . . . . . . . . . . . . . 9 5. Effect of panting on blood gases and pH . . . . 14 6. Previous studies on cats. . . . . . . . . . . . 19 7. Summary . . . . . . . . . . . . . . . . . . . . l9 STATEMENT OF THE PROBLEM. . . . . . . . . . . . . . . . 21 METHODS O O O O O 0 O O I O O O O O O O O O O O O O O O 2 2 1. Animals . . . . . . . . . . . . . . . . . . . . 22 2. Construction of implanted materials . . . . . . 22 3. Surgery . . . . . . . . . . . . . . . . . . . . 30 4. Care of animals . . . . . . . . . . . . . . . . 32 5. Equipment . . . . . . . . . . . . . . 32 6. Measurements. . . . . . . . . . . . . . . . 35 7. Experimental design . . . . . . . . . . . . 38 8. Calculations. . . . . . . . . . . . . . . . . 39 9. Analysis of data. . . . . . . . . . . . . . . 39 RESULTS . C C O O O O O O O O O O O O O O O C O O O O C 4 1 DISCUSSION. 0 O O O O O O O O O O O O O O O 0 O 0 . 0 . 67 CONCLUSIONS 0 O O O O O O I O O O O O O O O O O O O O O 8 l BIBLIOGMPHY O C O O O O O O O O O O O O O O O I O O O O 82 iii 3.31.3 OF CONTEI ‘DR':\"'\T VS 51:..341 u o l. Calibra 2. Average tempera 3. Aver ge thalari " ReSpire thalamj (.1 I . ReSpira Skin tg 6.p . aCOZ c 7. PaCOZ E 3. p . aCOz ¢ 9. p . aeoz c 10. PH as pH as PH as . ' P a a la P 02 15, P 302 53 16, PaO a TABLE OF CONTENTS--C0ntinued APPENDICES. . 12. l3. 14. 15. 16. Calibration curve for thermocouples. . Average skin temperature as a function temperature. . . . Average skin temperature as a function thalamic temperature . . . . . . . . . Respiratory frequency as a function of thalamic temperature Respiratory frequency as a function of skin temperature . PaC02 PaC02 PaC02 PaC02 pH as a pH as a pH as a as a function as a function as a function function of function of function of as a function of of rectal of hypo- hypo- average ambient temperature . . of average skin temperature. of rectal temperature. . of hypothalamic temperature. ambient temperature. . . . rectal temperature average skin temperature . a function of ambient temperature. . . a function of rectal temperature . . . a function of average skin temperature DJ iv function of hypothalamic temperature Page 90 92 94 96 98 100 102 104 106 108 110 112 114 116 118 120 122 1- Means and temperate: cats in a] 2- Means and and PH an: for all c. TABLE LIST OF TABLES Page Means and standard errors of body and ambient temperatures and respiratory frequency of all cats in all experiments. . . . . . . . . . . . . 42 Means and standard errors of blood gas tensions and pH and means of bicarbonate concentration for all cats in all experiments. . . . . . . . . 55 Schenatlg and acr 1 Lateral ); thalamic Cdl’lflllla. IEStraI ¢g‘.‘ Rectal ta tempera: MI ag e ”bier; FIGURE 10. 11. 12. 13. 14. LIST OF FIGURES Page Schematic drawing of cannula and stopcock. . . . 25 Schematic drawing of thermocouple guide tubes and acrylic disc . . . . . . . . . . . . . . . . 27 Lateral X-ray View of cat's head showing hypo— thalamic thermocouple guide tubes, stopcock, and cannula. . . . . . . . . . . . . . . . . . . . . 29 Schematic drawing of cat in exposure chamber and restraint device . . . . . . . . . . . . . . . . 34 Rectal temperature as a function of ambient temperature. . . . . . . . . . . . . . . . . . . 44 Average skin temperature as a function of ambient temperature. . . . . . . . . . . . . . . 46 Rectal temperature as a function of hypothalamic temperature. . . . . . . . . . . . . . . . . . . 49 Respiratory frequency as a function of ambient temperature 0 O O O O O O O O O O O O O O O O O O S 1 Respiratory frequency as a function of rectal temperature 0 O O O O O O O O O O O O O O O O O O 5 3 PaCO2 as a function of respiratory frequency . . 57 pH as a function of respiratory frequency. . . . 60 pH and plasma bicarbonate concentration as func- tions of PaC02 in resting cats . . . . . . . . . 62 Pao2 as a function of respiratory frequency. . . 64 Record of respiratory movements from a single cat 0 O O O O I O O O O O O O O O O O O O O O O O 6 6 vi I A homeothe dissipate both generated by t1: constancy. Whe: 6 fi .33“ .rature , E‘»'« .e ancil .gulation may Leary role 0 ad carbon (ho a exchang Qteeth ”my de “muons 53511113“ “Sous a 3h INTRODUCTION A homeotherm subjected to an acute heat stress must dissipate both the heat gained from the environment and that generated by tissue metabolism in order to maintain thermal constancy. When ambient temperature exceeds body surface temperature, evaporation is the sole avenue of heat loss available to the animal. Furred or feathered homeotherms face a further restriction in that most of their external body surface is not suitable as a site for evaporation. These animals must depend on evaporation from the surfaces of the nasal and buccal cavities and upper respiratory passages for maintenance of homeothermy during severe heat stress. The ancillary use of respiratory passages for thermo— regulation may, however, jeOpardize the fulfillment of the primary role of the respiratory system—~the exchange of oxygen and carbon dioxide. Maintenance of an appropriate rate of gas exchange requires that alveolar ventilation be regulated by the metabolic activity of the body, whereas defense of homeothermy demands that ventilation of the upper reSpiratory Surfaces be governed by the heat load on the animal. Simultaneous achievement of both functions implies a fine Imatehing of respiratory frequency and tidal volume, resulting i: nomotherni; Exper inae r: the precision '. ran. .31 alveola: parting. The n in normothermia with normal blood pH and blood gas tensions. Experiments reported here were designed to elucidate the precision with which the furred homeotherm maintains normal alveolar ventilation during hyperthermally induced panting. The unanesthetized cat was used as a model. 1L. .- Defiflition C Although t heat stress ha? sinc e the en:3 0 standardized te 3::- ...... et (1898? T as 'a facilitat .ater authors I“. ‘ gym ‘1‘ a designated and-Grodins, 19 reserved the te freqaency acco: , relaxati "ongue ( orster re: t0 , 15 REVIEW OF THE LITERATURE 1. Definition of terms Although the respiratory responses of homeotherms to heat stress have been the subject of scientific investigation since the end of the nineteenth century, there has been no standardized terminology to describe the observed phenomena. Richet (1898; quoted in Richards, 1970a) defined "panting" as "a facilitated form of rapid shallow respiration". Some later authors have chosen an arbitrary respiratory frequency and designated all frequencies above this as panting (Lim and Grodins, 1955; Baldwin and Ingram, l968). Others have reserved the term "panting" for an elevated respiratory frequency accompanied by retraction of the angles of the mouth, relaxation of the lower jaw and protrusion of the tongue (Forster and Ferguson, 1952; Andersson gt 31., 1956). Those who use this restricted definition often designate a high respiratory frequency without accessory head movements as "polypnea". Other authors treat "polypnea" as a synonym for "panting", regardless of their criteria for “panting". The term "tachypnea" also is used, especially in the older literature, to designate an elevated respiratory frequency. In this review, "panting" will refer to increased respiratory I‘ —'I 'ifl‘h‘“ frequency with aill designate The use oi difficulty in a are show that heat stress bot‘ Bligh. 1966). 1.1059 ObSErVat '1 L' P"I’l’lo'e'ehetic and Ranting Respirato :rigmated e91 ieaelo‘gEG in t irinant form in: bil‘ds. LiZardS frequency with accessory mouth movements, while "polypnea" will designate simply increased respiratory frequency. The use of anesthetized animals is a further source of difficulty in appraising research on panting. Many studies have shown that anesthesia disrupts the panting response to heat stress both in mammals and in birds (Albers, 1961a; Bligh, 1966). In this review, emphasis will be placed on those observations made on unanesthetized animals. 2. Phylogenetic distribution of polypnea and panting Respiratory evaporative water loss appears to have originated quite early in evolutionary history. It is best deveIOped in the homeotherms (birds and mammals), and is the dominant form of evaporative heat loss in furred mammals and birds. Lizards are the oldest animal forms in which either polypnea or panting have been reported. Some desert species pant when body temperatures exceed 42°C (Richards, 1970a). Others do not pant, but instead exhibit rhythmic, high- frequency movements of the ventral neck region ("gular pump- ing"; Bartholomew and Tucker, 1964). Many birds, except some species native to arctic or nuauntain regions, include panting among their responses to heat (Salt, 1964). Some birds display gular flutter simul- taneously with panting, although it may not be synchronized Witfli the panting rhythm (Calder and Schmidt-Nielsen, l968). Among Fri: altnough they T temperature ap; 19706.). Most «'7 addition (Richs widespread, hav anadillos (Ric \K) . 42), goats I’ {I 'a‘ebster, 1967) . Taylor, 1969). liamouda, 1932 :ainea pigs, a‘ at‘ares (Richer 13W. cattle 3:9) Sweating aw “r’VSI-Ire o 5' Control of The cont: azeteenth ceI .i‘r‘ - . «Ch Ulltiat‘ Im' “51“ undete as an. “wothala i9“. rerature ' All YSensibl Among primitive mammals, prototheres do not pant, although they may elevate respiratory frequency when body temperature approaches the upper lethal limit (Richards, 1970a). Most metatheres exhibit polypnea, and many pant in addition (Richards, 1970a). Among Eutheria, panting is wideSpread, having been reported in bats (Richards, 1970a), armadillos (Richards, 1970a), rabbits (Hiestand and Randall, 1942), goats (Andersson gt 31., 1956), sheep (Hales and Webster, 1967), cattle (Bianca, 1955), many African ungulates (Taylor, 1969), pigs (Mount, 1962), and dogs and cats (Hammouda, 1933). Panting has not been observed in rats or guinea pigs, although polypnea occurs at raised body temper- atures (Richards, 1968). In sheep (Alexander and Brook, 1960), cattle (McLean, 1963), and some African bovids (Taylor, 1969) sweating and panting occur simultaneously during heat exposure. 3. Control of panting The control of panting has been studied since the late nineteenth century, but the precise nature of the stimuli Which initiate panting, as well as their mode of integration, .remain undetermined. Considerable evidence indicates that 'the hypothalamus is essential for the regulation of body temperature, and also that this region of the brain is ther- mallysensible (see reviews by Hardy (1961), Bligh (1966), and! Hammel (1968)). Early workers were concerned largely with the relative (chiefly SK '1: the use of a- the relative importance of central (brain) and peripheral (chiefly skin) stimulation in the initiation of panting. The use of anesthetics and the crudeness of apparatus em- ployed for heating the brain complicate the interpretation of most of these studies. Experiments during the last twenty years using increasingly sophisticated techniques applied to unanesthetized animals demonstrate that in sheep (Bligh, 1959), cattle (Bligh, 1957a,c; Findley and Ingram, 1961), dogs (Hales and Bligh, 1969), and some cats (Forster and Ferguson, 1952) panting can occur as a result of peripheral thermal stimulation without a rise in deep body temperature. In most cats (Forster and Ferguson, 1952; Adams gg_gl., 1970), pigs (Mount, 1962), goats (Andersson g3 g1., 1956) and chickens (Richards, 1970b) panting does not occur unless deep body temperature rises above its thermoneutral range. Direct, localized heating of the thermosensible area of the anterior hypothalamus can initiate polypnea or panting in cattle (Ingram and Whittow, 1962a), cats (Hunter and Adams, 1971), dogs (Hammel gg g£., 1963), pigs (Baldwin and Ingram, 1968) and rabbits (von Euler, 1964). The response to hypothalamic heating is progressively diminished by decreasing ambient and skin surface temperatures, and enhanced by increases in these temperatures (Randall and Hiestand, 1939; Lim and Grodins, 1955; Ingram and Whittow, 1962a; Baldwin and Ingram, 1968; Hunter and Adams, 1971). The influ respiratory su its considerat trailer. Hunt: zionship betwe' nanesthetized ship is altere tire cooling 0 cooling of the The tenperatur considered re; 595‘! Sites. r Elleratures n 2301.199 in re: ‘EAPEIatUre (I turn diminish! The influence of evaporative cooling of the upper reSpiratory surfaces on hypothalamic temperature complicates its consideration as an input to the thermoregulatory con- troller. Hunter and Adams (1966) have shown that the rela- tionship between hypothalamic and rectal temperatures in the unanesthetized cat is linear, but the slope of the relation- ship is altered by panting. They demonstrated that evapora- tive cooling of the upper reSpiratory tract causes local cooling of the ventral brain, including the hypothalamus. The temperature of the hypothalamus cannot, therefore, be considered representative of the temperatures of other deep body sites. Nevertheless, extrahypothalamic deep body temperatures modify thermoregulatory activity. Evaporative cooling in response to hypothalamic heating lowers deep body temperature (Hammel gg’gl., 1960; von Euler, 1964), which in turn diminishes the response to the central thermal stimulus. The location of the receptors by which extrahypothalamic deep body temperatures are transduced remains unknown. Localized heating of the spinal cord has been reported to initiate panting in dogs (Jessen and Mayer, 1971) and rabbits (Kosaka g2 31., 1969) and to cause increased cutaneous and respiratory evaporative heat loss in oxen exposed to a hot environment (McLean gg gl., 1970). Reflex panting has been initiated by heating the scrotum of the ram (Hales and Hutchinson, 1971) and the pig (Ingram and Legge, 1972) and the udder of the goat (Linzell and Bligh, 1961) and the ewe I) (Phillips and and Rag..avan ( tors in the u; pate in the cc implicated the V ”a. -..rnoregulatc anesthetized in the fowl , :iltlng Ihies (Phillips and Raghavan, 1970b). Bligh (1963) and Phillips and Raghavan (1970a) have suggested the existence of recep- tors in the upper respiratory tract of sheep which partici— pate in the control of panting. Rawson and Quick (1972) implicated thermosensitive elements in the gut of sheep in thermoregulatory responses to heat stress. The role of the vagi in controlling panting is species- dependent. Double vagotomy does not affect panting in the anesthetized rabbit, lamb, or pigeon (Richards, 1968), while in the fowl, double but not unilateral vagotomy abolishes panting (Hiestand and Randall, 1942). Double vagotomy has little effect on respiratory frequencies during panting in the anesthetized dog (Albers, 1961b), although it may cause a more abrupt onset and cessation of panting (Anrep and Hammouda, 1933). During the onset of panting, the Hering- Breuer inflation reflex mediated by the vagus disappears gradually in anesthetized dogs (Hammouda, 1933) although it persists at a reduced level in the panting duck and to a larger extent in the rabbit (Hiestand and Randall, 1942). The role of the cerebral cortex in the panting response also varies with Species. Hammouda (1933) described panting as a conditioned reflex in dogs, since after multiple ex- posures of one animal to 45°C ambient temperature, the latent period before the onset of panting decreased from eight minutes to thirty seconds. In chickens, however, such "learning" did not occur, even after 100 exposures (Richards, 1970b). Relativ of thermal V Eamouda (1' in the anes arterial bl dioxide cau the frequer dioxide res in tidal v< that the s was decree 21' ‘ '1 ‘ . GDSCI'E C1 Relatively little work has been done on the integration of thermal with chemical drives to respiration. Anrep and Hammouda (1933) found that hypoxia did not prevent panting in the anesthetized dog until oxygen saturation of the arterial blood fell below 80%. Inhalation of 2% carbon dioxide caused an increase in tidal volume but no change in the frequency of panting. Higher concentrations of carbon dioxide resulted in a decline in frequency and a further rise in tidal volume. Albers (1961c) found in anesthetized dogs that the slope of the minute ventilation--PaCO response curve 2 was decreased and the intercept was shifted to a lower CO2 pressure during panting. In contrast, the slope of the alveo- lar ventilation-- response curve was unchanged by either PaCO2 polypnea or panting, although the intercept was shifted to progressively lower CO tensions as respiratory frequency 2 rose during panting. Since an increment in body temperature increased minute and alveolar ventilation more when body temperature was high, Albers concluded that the thermal drive is additive to the chemical one, but in a non-linear fashion. 4. Respiratory pattern and site of evaporative cooling When the unanesthetized dog is initially exposed to heat, reSpiratory frequency is unchanged or may even decline. As the heat stress continues, respiratory frequency increases, ‘while tidal volume remains unchanged. Consequently, minute ‘ventilation increases, reaching 3.5 times the control value before panting. this period of INKS as 8001‘. mtabrupt; sh Ely-pnea. The Elements 53 D » V\ L. . .zec docs a“: rating is co sf alscontinu' anesthetized as achient an narrating tin free. 1953} ‘J n sheep 9‘ . \' “l K" 1971) 53-‘i . K Elle S . to I’m "4 . this 0 ‘;~ .811 10 before panting is initiated. The dog appears restless during this period of polypnea, but the apparent discomfort disap- pears as soon as panting begins. The onset of panting is not abrupt; short bursts of panting begin to interrupt the polypnea. The panting bursts consist of rapid thoracic movements superimposed on a tonic abdominal inspiration. During panting bursts the tidal volume declines to about 75% of the control value (Hemingway, 1938). Albers (1961a) observed that respiratory frequency in- creases continuously as body temperature rises in anesthe- tized dogs, while the alternation of polypnea with bursts of panting is confined to the unanesthetized animal. The pattern of discontinuous episodes of panting occurs also in the un- anesthetized pig (Ingram and Legge, 1970). In both Species, as ambient and skin temperatures rise the polypneic intervals separating the panting bursts become shorter, and respiratory frequency during both polypnea and panting increases. The decline in tidal volume at the onset of panting occurs in cattle (Bianca and Findlay, 1963; Taylor gg g£., 1969), sheep (Hales and Webster, 1967), and goats (Heisey ‘g2_g1., 1971). In the pig, tidal volume declines only until frequency reaches lOO/min, then stabilizes as frequency continues to rise (Ingram, 1964). The wildebeest departs from this general pattern, since its tidal volume is main- tained at control values during polypnea and panting (Taylor gt; _a_1_._., 1969) . The ostrich responds conversely to the ramalian patt from S/rnin to it higher arbi steadil" incre so tidal vol: 5‘35? te-‘fiperai: .. A , zzras snift a 151:8 the nat ‘L n EN \al'oreg‘lla s‘. . .ECuSl, r? «A HE T‘Nn §~\"V ‘~~'r‘ ‘ Y 52‘: A H e: k the up, t. . ll mammalian pattern. Its respiratory frequency rises abruptly from 5/min to 45/min when ambient temperature exceeds 25°C. At higher ambient temperatures the evaporative water loss steadily increases despite the constant respiratory frequency, so tidal volume is presumed to increase Wlth elevations in body temperatures (Crawford and Schmidt-Nielsen, 1967). Some birds shift abruptly to a respiratory frequency which approxi- mates the natural resonant frequency of the chest for that species. Other species display a gradual increase in respira- tory frequency which is linearly related to body temperature (Richards, 1970a). The pattern of ventilatory movements during panting is important because borrowing respiratory functions for thermo- regulation could interfere with the normal, strict control of alveolar ventilation which maintains blood pH and gas content within physiological limits. The extent to which thermoregulation and blood gas regulation can proceed simul- taneously depends to some extent on the portion of the respiratory tract from which evaporative cooling occurs. If evaporation took place in the alveoli, an increase in evapor- ative water loss would obligate augmented alveolar ventila- tion and interfere with blood gas regulation. Alternatively, if vaporization of sufficient water occurs as air passes over the upper respiratory tract during respiration, the two functions of evapOration and gas exchange should be separable by matching an increase in frequency with a reduction in tidal solute. Blig‘; in the poison: panting calf ‘ not occur in C: baSal bra 5...: AdaI‘s 12 volume. Bligh (1957b) found the temperature of the blood in the pulmonary artery and in the bicarotid trunk of the panting calf to be the same, suggesting that evaporation does not occur in the alveoli. The temperature of the blood drain- ing into the external jugular vein of the ox decreases markedly during panting (Ingram and Whittow, 1962b). The site of vaporization would consequently appear to be the nasal and buccal cavities, which are drained by the external jugular vein in this species. Similarly in the cat, evapora- tion from the roof of the mouth resulted in localized cooling of basal brain structures including the hypothalamus (Hunter and Adams, 1966). In the large African ungulates, blood cooled by evaporation in the complex nasal cavities passes through a counter-current heat exchange system in the carotid rete, cooling the arterial blood before it reaches the ventral brain region and enabling these animals to maintain a differ— ence of several degrees C between hypothalamic and rectal temperatures during severe heat stress (Taylor, 1969). Since evaporative cooling occurs in the upper respiratory tract which constitutes part of the deadspace, the amount of heat lost would be expected to depend upon deadspace ventila- tion rather than on alveolar ventilation. In cattle, the ratio of alveolar to total ventilation declines as total 'ventilation rises during panting, and the ratio of deadspace 'volume to tidal volume increases (Hales and Findlay, l968a). Such.an arrangement would facilitate a desirable separation 13 of evaporatory and gas exchange functions. Albers (1961a) reported a similar situation in the dog: deadspace volume increased linearly with tidal volume at any given frequency, but the slope of the relationship became steeper the higher the frequency. The pattern of panting in which tidal volume is dimin- ished as respiratory frequency rises is referred to as "Phase I" breathing, and predominates during mild and moder- ate heat stress. In very severe heat stress, tidal volume begins to increase as respiratory frequency reaches its peak (Albers, 1961a). Frequency then declines, returning approximately to the control level as tidal volume continues to increase (Bianca and Findley, 1962, cattle; Hales and Webster, 1967, sheep; Hales and Bligh, 1969, dog). In the chicken (Whittow gg_g$., 1964) and the anesthetized cat (Samek g5 gl., 1970), frequency declines at very high body temperatures. In the pig (Ingram and Legge, 1970) and the goat (Heisey gg gl., 1971) tidal volume increases during very severe heat stress. Respiratory frequency stabilizes when tidal volume increases in the pig, but frequency continues to rise despite the elevated tidal volume in the goat. The pat- tern common to cattle, sheep, and dogs, i.e., decreased fre- quency and elevated tidal volume, has been designated "Phase II“ breathing (Bianca, 1958). The shift from Phase I ‘tchhase II breathing is not correlated with rectal tempera- thre (Hales and Bligh, 1969). Phase II panting cannot be initiated by ': My temperate hymthalamus r. body temperate During Ph alveolar, dead heaSured at U". crease in alVe in deadspace a Cdttle; H3183 ‘le $10»;ng a: ta U l4 initiated by heating the hypothalamus unless skin and deep body temperatures are at hyperthermic levels, and cooling the hypothalamus will not prevent its appearance if the other body temperatures are high (Findlay and Hales, 1969). During Phase II panting in both sheep and cattle, alveolar, deadspace and total ventilation increase over values measured at the peak of Phase I breathing, although the in- crease in alveolar ventilation is more marked than the changes in deadspace and total ventilation (Hales and Findlay, 1968a, cattle; Hales and Webster, 1967, sheep), as expected from the slowing and deepening of the respiratory rhythm. Respira- tory evaporative water loss during Phase II panting exceeds that at the peak of Phase I breathing (McLean gg g£., 1970). 5. Effect of panting on blood gases and pH Disturbance of alveolar ventilation during panting is minimized by decreasing tidal volume and by maintaining a tonic abdominal inspiration during the high frequency breath- ing. The success of these compensatory maneuvers will largely determine the animal's ability to maintain normal acid-base balance during heat stress. In the unanesthetized ox exposed to moderate heat stress which evoked Phase I breathing only, Hales and Findlay (l968a) reported that Pa02 rose 5 mm Hg above control, while PaCOZ declined 5 mm Hg and arterial blood pH rose 0.03 units. Albers (1961a) reported that, in ‘the unanesthetized dog, arterial pH, bicarbonate concentration, O) 9 P A3 I I a ' C32 02 capacity are 1; NR (the res in ad during pan '50? during the Scott (1923) f 15 Paco , Pa0 , and arterial blood oxygen saturation and oxygen capagity aie unchanged during moderate heat stress (PhaSe I), and R (the respiratory exchange ratio) remained at 0.8 before and during panting. In contrast, Shelley and Hemingway (1940) reported that R decreased rapidly in the unanesthetized dog during the first half hour of heat stress, and Flinn and Scott (1923) found that unanesthetized dogs exposed to 40°C ambient temperature had a decrease in venous blood CO2 con- tent, although the venous pH remained within "normal limits" (7.55). Hemingway and Barbour (1938) reported that dogs treated with diathermy so that their heat production rates were one, two, or three times their BMR had lowered PaCO but showed no change in arterial blood pH. 2 At least two factors contribute to the maintenance of normal pH in the face of lowered P First, during acute O O C 2 heat stress in the Ayrshire calf, the kidneys compensate for the hyperventilation by producing alkaline urine, so that venous pH is unchanged despite a fall of venous PCO from 2 35-40 mm Hg in the control to 27 mm Hg during panting (Bianca, 1955). Fuller and MacLeod (1956) showed that excretion of acid and ammonia fell during hyperventilation in dogs, while bicarbonate excretion increased. Second, excess lactate appears in the blood of panting oxen during exposures to 40°C dry bulb/38°C wet bulb (Hales gg g£., 1967). Burshtein and Tilis (quoted in Richards, 1970a) have shown that acid retabolites a Frankel gt 2 in the blood . and Posner (1. caused the a; from the brai: H.923) demons: 16 metabolites accumulate in the blood of heat-stressed dogs. Frankel g5 gl. (1963) observed that excess lactate appeared in the blood of dogs when Phase II breathing began. Plum and Posner (1967) reported that hyperventilation in dogs caused the appearance of excess lactate in blood draining from the brain but not in arterial blood. Anrep and Cannan (1923) demonstrated that the accumulation of lactate in the blood during hyperventilation is not dependent on P0 or 2 blood oxygen saturation, but is directly related to the extent of over-ventilation. This was confirmed by Frankel (1965) who showed that in artificially respired chickens inhaling CO hyperventilation produced no excess lactate unless the 2' CO2 concentration of the inSpired gas was less than 5%. Although several factors act to maintain normal blood pH during panting, as respiratory frequency reaches its peak the compensatory ability of these factors is exceeded, and Pao 2 and pH rise while PaCO falls substantially below control. 2 In cattle, blood pH begins to rise during the final part of Phase I breathing, and reaches 7.78 during Phase II panting (Bianca and Findlay, 1962). The elevated pH is accompanied by a fall of PaCO from 45 mm Hg (control) to 17 mm Hg 2 (Bianca and Findlay, 1962). Tetany was observed in two oxen in which PaCO had fallen below 10 mm Hg and pH exceeded 7.8 2 (Hales and Findlay, l968a). In sheep also, when respiratory frequency peaks-during Phase I panting, venous pH rises from the control value of 7.38 to 7.67, and PvCO falls from 42 mm 2 :9 to 24 nun r1 declines stea Sales and Eli with small ele frequency in t found that the hours had nor? exposed to 45: hour. Dogs ex 7.84 when they‘ injury. entered Phase served arteria.‘ :nase II breatl «HLIdt‘NIEISEI l7 Hg to 24 mm Hg (Hales gg gl., 1970). In the goat, PaCO 2 declines steadily as frequency rises (Heisey g: gl., 1971). Hales and Bligh (1969) reported a slight decline in PaCO 2 with small elevations in PaO and pH at maximum respiratory frequency in the unanesthetiged dog. Flinn and Scott (1923) found that the venous blood of dogs exposed to 40°C for six hours had normal pH values, whereas the blood of those dogs exposed to 45°C had an average pH of 7.79 at the end of one hour. Dogs exposed to 50°C had venous blood pH values of 7.84 when they were removed from the heat stress to prevent injury. No mention was made of whether these dogs had entered Phase II respiration. Hales and Bligh (1969) ob- served arterial pH values of 7.77 with PaCO2 at 4 mm Hg in Phase II breathing in one unanesthetized dog. Calder and Schmidt—Nielsen (1968) studied the effects of panting on acid-base balance in a number of avian species. In some, panting was associated with no change in either PaCOZ or pH, whereas in others pH values as high as 7.86 and carbon dioxide tensions as low as 8.6 mm Hg were observed. The hypocapnia which develops at the end of Phase I pant- ing would be expected to counteract the thermal stimulus for reSpiration if it led to reduced brain tissue PCO or in- 2 creased brain tissue pH. Brain tissue PCO cannot be measured 2 in the unanesthetized animal, but the PCO in the vicinity of 2 the medullary chemoreceptors can be estimated if the gas tensions of blood and cerebrOSpinal fluid (CSF) are known. Hales g2 a1 an increase P. from 4 Caz the same 611 3"3.1319 Phas ling at 7. The fall if. NiCXide te: antes aft In); wit; r633. , 18 Hales gg gl. (1970) found, during Phase I breathing in sheep, an increase of CSF pH from 7.32 to 7.47, and a fall of CSF PCO from 41 mm Hg to 29 mm Hg. These changes in CSF are in 2 the same direction but are smaller than those in the blood. During Phase II panting, CSF pH peaked at 7.59 before stabil- izing at 7.50, and CSF P declined from 29 to 18 mm Hg. C02 The fall in CSF pH (from 7.59 to 7.50) while CSF carbon dioxide tension was constant or falling reflected a reduction in CSF bicarbonate concentration. That these changes in the CSF are likely to reflect those in brain tissue is suggested by Ponten (1966), who found that changes in brain tissue CO2 content in hyperventilated rats were complete within thirty minutes after a step-change in PaCO . 2 Decreased P and alkalosis would be expected to in- CO2 hibit respiration, but Chapot (1967) found in cats that lowered arterial PCO caused a large increase in phrenic nerve discharge, in a pattgrn similar to that during thermal panting. Pleschka (1969) observed that, in anesthetized dogs, artificial hypertilation produced polypnea, even if body temperatures were relatively low. The role of this effect in the normal response to heat stress remains to be evaluated. Hypocapnia resulting from severe panting would be ex- pected to influence brain blood flow, since Hayward (1966) reported that a 2% decrease in end-expired CO2 caused a de- crease in blood flow to the brain of the monkey, and Serota ad Gerard halation i 5. Previcu Anrep thetized c 2‘3CC When ‘ t‘33.;eratur. from 24 to 19 and Gerard (1938) showed in anesthetized cats that CO2 in- halation increased brain blood flow. 6. Previous studies on cats Anrep and Hammouda (1933) studied panting in one anes— thetized cat and reported that tidal volume declined from 20cc when rectal temperature was 37°C to 9.3cc when rectal temperature reached 39°C, while respiratory frequency rose from 24 to 370/min. Samek gg'gi. (1970) reported a decrease in respiratory frequency in anesthetized cats exposed to severe heat stress. Von Euler gg gi. (1970) found that tidal volume increased in anesthetized or decerebrate cats which displayed polypnea but not panting when heated to rectal temperatures of 39.6°C. Blood gas pressures in resting unanesthetized cats have been obtained by two methods. Fink and Schoolman (1962) used chronic intra-arterial cannulae to obtain blood samples, and reported an average blood pH of 7.38 with a Paco of 28 mm Hg. Sorenson (1967) used samples of gas which had been equilibrated with tissue in subcutaneous gas pockets to obtain a value of 29.9 mm Hg for PaC02° Herbert and Mitchell (1971), employing intra-arterial cannulae, reported an average pH of 7.426 and a of 32.5 mm Hg. Pa 0 C2 7. Summary Polypnea and panting are common responses to heat stress among mammals and birds. During moderate heat stress, most panting 5:26 and reduce: are avoidec pattern is ski 20 panting species display increased respiratory frequencies and reduced tidal volumes so that hypocapnia and alkalosis are avoided. During severe heat stress, the respiratory pattern is altered and both hypocapnia and alkalosis develop. BXperiner thetized cats Pan-ting, and 1 2.5331 blon OX} ”A. com; letins the °5 a snail fu] aderstanding System interac Italian bod. STATEMENT OF THE PROBLEM Experiments were designed to determine whether unanes- thetized cats exposed to mild, moderate, and severe heat stress become hypocapnic or alkalotic during polypnea and panting, and to quantify the effects of polypnea and panting upon blood oxygen tension. These data will be of value in completing the description of the thermoregulatory responses of a small furred homeotherm, and will also contribute to an understanding of the manner in which the thermoregulatory system interacts with other homeostatic mechanisms in the mammalian body. 21 1' Animals All ex; CannUI ’Silastic M 0.3. .047 i Pct Cat No. its“, 0a, METHODS 1. Animals All experiments were conducted on adult, short-haired male or non-pregnant, female, domestic cats. The animals were housed in cages in the laboratory, exposed to approxi- mately 14 hours of light per day, and fed "9-Lives" dry cat food (Star-Kist Foods, Inc.). Water was available ad. lib. Five cats were used in the study: cat No. l, a 4.1 kg male; cat No. 3, 2.3 kg, female; cat No. 5, 2.9 kg, female; cat No. 6, 3.4 kg, male, and cat No. 7, a 3.0 kg female. 2. Construction of implanted materials Blood samples were drawn from a chronically implanted cannula connected to a modified two—way stainless steel stop- cock (Figure l) which was anchored to the skull as shown in Figure 3. Cannulae were made from two lengths of Silastic tubing (Silastic Medical Grade Tubing, No. 602-151; i.d. .025 inch, d.d. .047 inch; Dow Corning Corp., Midland, Michigan 48640). For cat No. 1 only, the tubing was No. 602—171, i.d. .030 inch, o.d. .065 inch. One end of each Silastic tube was Slipped over a 1.5 cm length of Teflon tubing (Teflon Medical 22 Grade Tubing r o.d. .030 incl“. 2:. J.). The t over the Teflc .‘-., Dow Corning section around each cannula w :lct formation rPine upper length of 21-9: scldered into (41 Dickinson and f“) .A ah" by“: tructed fr: 1 "A - . “thematic are figure 1. I HYPOthalar- | I*' hrai «n, and Whic Cent . a1 acryl 1c v ‘3Jres 2 a d "“9195 wer ma 26‘9au 99 needl wilvet‘ Grade Tubing, No. 6425, ultra-thin wall; i.d. .018 inch, o.d. .030 inch; Becton, Dickinson, and Co., Rutherford, N. J.). The two Silastic sections were cemented together over the Teflon with Silastic Medical Adhesive (Silicone Type A, Dow Corning; Figure 1). This construction provided a rigid section around which ligatures could be placed. The lumen of each cannula was coated with Siliclad (Clay Adams) to inhibit clot formation. The upper end of each cannula was fitted over a 5 mm length of 21-gauge needle stock (o.d. .0325 inch) which was soldered into a modified stopcock (Model MSOl or M804, Becton, Dickinson and Co.). For cat No. 1 only, the adaptor was constructed from stainless steel tubing, o.d. .054 inch. .A schematic drawing of cannula and stopcock is presented in Figure l. Hypothalamic temperature was measured by a 40-gauge, c0pper-constantan thermocouple inserted into guide tubes which had been surgically implanted, bilaterally, into the brain, and which were secured to the skull surface using a dental acrylic housing and small, stainless steel screws (Figures 2 and 3). Guide tubes for the hypothalamic thermo- COuples were made by sealing one end of a 35 mm length of 20‘gauge needle stock (o.d. .0355 inch) with resin core, Silver-lead solder. Two guide tubes were embedded in a disc 0f dental acrylic (NuWeld, L. D. Caulk Co., Milford, Del., 199653). Twenty-seven mm of guide tube extended below 24 mcHqu coamoe n BB m>flmo£©m HMUfiooz UHDmmaflm u «Em ocean“ UHUonHm n Em HmpHOm n um Hoummom H < xooomoum u om .xooomoum paw masccoo mo mcfl3mno oaumamsom .H musmfim 25 H ounmam .5 V\. Figure 2. 26 Schematic drawing of thermocouple guide tubes and acrylic disc. GT = guide tube SP = solder plug AD = acrylic disc 27 l/2 in. ___G;‘r. 4- Hi—su= Figure 2 28 .mmulx map CH wHQHmH> DH mme Op ESHUmE ummuucoo nufl3 Umaaflm mMB wasccmo mQB .masccmo can .xooomoum .monsu wcfism oamsoo IoEHmnu OHEmHmnwommz mGHBOnm pom: m.umo mo 3wH> >mnnx Hmumumq .m musmflm 29 m onsmflm 3m botton Stoner Mud 3.Surgery Arter attachment trier a gal Pentobarbit 111., 60064 §i'v'en as he tained. The fo 30 the bottom of the disc (Figure 2). Tubes were insulated with Stoner Mudge Protective Coating (S-986-S). 3. Surgery Arterial cannulation, implantation of guide tubes and attachment of connectors to the animal's skull were performed under a general anesthetic. The initial dose of sodium pentobarbital (Nembutal; Abbott Laboratories, North Chicago, 111., 60064) was 36 mg/kg, administered ip. Supplements were given as necessary, iv or ip. Aseptic precautions were main- tained. The following procedures were used for the implantation of cannula and guide tubes. The skin and fasciae overlying the skull were incised and, together with the underlying muscles, retracted. The thermocouple guide tubes, fixed in the acrylic disc (Figure 2), were implanted stereotaxically in the preOptic region of the anterior hypothalamus (stereo- taxic frame: Model 1204, David Kopf Instruments, Tujunga, Calif., 91402; guide tubes positioned according to Snider and Niemer, 1961; coordinates: 14.5 mm anterior and 6 mm dorsal to the interaural line, 3.5 mm on either side of the midline). Three stainless steel screws (MS 256-6F, Small Parts Inc., Miami, Fla.) were screwed into holes drilled in the skull. The stopcock, with cannula attached, was placed adjacent to the acrylic disc and additional acrylic was poured around screws, stopcock, and disc, as well as over the edges of the incised sk done with stopcock. A mid the muscle exposed, c The artery In P v. I SiZe Iron the t. 59: ion of CA“ .ourth rib “s . sue tlp WC] {as fillEd i’: “S Spray8( V4,; ..iqland’ V: n t‘. ~annula thw 31 incised skin. On all cats except No. l a protective plastic dome with access holes was cemented with acrylic over the stopcock. A mid-ventral incision was made in the skin of the neck, the muscles were retracted and the left common carotid artery exposed, care being taken to avoid injuring the vagus nerve. The artery was ligated cranially with silk suture (Ethicon, Inc., size 0, M-404). The cannula was threated subcutaneously from the tOp of the skull to the neck incision, and the lower section of Silastic was trimmed so that its tip lay over the fourth rib. This insured that when the cannula was in place the tip would lie in the aorta. The lumen of the cannula was filled with 1% heparin solution (Sodium Heparin, 1000 units/m1; Upjohn, Kalamazoo, Mich., 49001) and the exterior was sprayed with a lubricant (Antiform A, Dow Chemical, Midland, Michigan). The carotid artery was cannulated and the cannula threaded down the artery until the small Teflon sec- tion lay just inside the vessel. Two ligatures (Ethicon, size 0, M-404) were placed firmly over the artery where it covered the Teflon section. The wound was closed with a non- capillary suture (Vetafil Bengen, Dr. S. Jackson, Washington, D. C., 20014). A long-lasting penicillin preparation (Long- icil, 30,000 units/1b; Fort Dodge Laboratories, Fort Dodge, Iowa) was injected intramuscularly. 4. Care Of At lee experiment . cannula flu to rest in and were ac mental pro 5. Equipmen a. Res Tue re. q'diEtly dur. aluminum fre The cat ' S he 32 4. Care of animals At least one week elapsed between surgery and the first experiment. The fluid in the cannula was withdrawn and the cannula flushed with 1% heparin daily. Animals were trained to rest in the restraint device (described below; Figure 4) and were accustomed to the chamber (Figure 4) and the exper- imental procedures before data collection began. 5. Equipment a. Restraint device The restrainer, in which animals were expected to rest quietly during each experiment, consisted of a brass and aluminum frame from which was suSpended a plastic mesh sling. The cat's head was held by a plexiglass yoke; the feet ex- tended through holes in the sling to rest on a wide-mesh wire screen (Figure 4). b. Chamber The exposure chamber (Figure 4) was constructed of plexi- glass (Polycast Technology Corp., Stamford, Conn.). The walls, floor and ceiling were 1/4 inch thick; the chamber was 28 inches long, 24 inches high and 13 inches wide. One fan drew air from the chamber over a dehumidifier (Sears, Roebuck and Co., Coldspot), then through a duct to the heat exchanger. Chamber temperature was controlled by regulating the flow of hot or cold water to the heat exchanger; water flow was con- trolled by a YSI Thermistemp temperature controller (Model 71, 33 i ! h \ .Pi “ w I HF \ KN .30Hm Ham mo cofluoouflo oDMOHUsfl m3ound Ham» mma mafia HOBOH moa Una: Homes poemmuow ummno poo: now u and H35 w :0 n o "ucoEoHSwmoE musumummfiou cflxm mo mopflm mumoflosfi muouuoa HHmEm Hoaaouvcoo wusumuomfiou monfioso How Homcom u m ummcmnoxo pom: n m WCMM H .m .HHOU HmAMHUHEDQmp n on mucouuso Mam uoouflp Eoum poo: m.pmo uoououm 0p mammmn u md .00H>o© usflmnumon can HoQEmno oHSmomxo :H umo mo mcflzmup oapwEonom .v ousmflm v wuflmflm Z 4 3 acct». 2 O 3232 E... 2 0 m4 .. 3.239.223... .3523 2 7 la]? g) l EFT-"‘1 Yellow Sprl stream frot- Cver the he into the Chi was maintair an Abbeon CE a thermocou; avoided suf thermal laye. points in th: Renovabl 35 Yellow Springs, Ohio), the sensor of which was located down— stream from the heat exchanger. A second fan drew air over the heat exchanger and forced it through a second duct into the chamber. Relative humidity of the air in the chamber was maintained at 35-40% in all exposures and was measured by an Abbeon Certified Hygrometer (Model AB 167, Abbeon, Inc., Jamaica, N. Y., 11432), mounted on the back wall of the chamber. Chamber temperature was continuously monitored with a thermocouple and was regulated to w1thin 0.1°C. The fans provided sufficient air movement within the chamber to prevent thermal layering; maximum temperature difference between points in the chamber was 0.2°C. Removable ports in the side of the chamber permitted access to its interior without gross disturbance of chamber temperature and relative humidity. A small hole in the front allowed passage of the blood sampling tube. 6. Measurements Skin temperature was measured at seven sites: ear (center, inner surface of pinna), head (center back of skull), forefoot (dorsal surface), chest (midlateral surface at pos— terior margin of rib cage), upper hind leg (midlateral sur- face), lower hind leg (mid-dorsal surface), and tail (midway between base and tip). Skin temperatures were measured with 36-gauge copper-constantan thermocouples referenced to an ice- water bath and attached to small areas of skin which had been cliPPEd and Labs., Inc. coated lighf and the the: of thin, pla £131.). Rec thermocouple beyond the e. C Q19 base of 1 'iith a 40-ga1 (“gauge need ”Marl way; ‘ 9 guide hv‘ Crasher air t couple suspen ture was reco: aultipoint re< The calibratic Phenom 1. 36 clipped and freed of hair by a depilatory (Neet, Whitehall Labs., Inc., N. Y., N. Y., 10017). The skin areas were coated lightly with Ace Adherent (Becton, Dickinson and Co.), and the thermocouples were held in place with small squares of thin, plastic surgical tape (Blenderm, 3M Co., St. Paul, Minn.). Rectal temperature was measured with a 36-gauge thermocouple mounted in polyethylene tubing, inserted 10 cm beyond the external anal sphincter and fastened with tape to the base of the tail. Hypothalamic temperature was measured with a 40-gauge thermocouple soldered into a 35 mm length of 24-gauge needle stock and lowered to the bottom of the thermo- couple guide tubes implanted in the anterior hypothalamus. Chamber air temperature was measured with a 36-gauge thermo- couple suspended from the roof of the chamber. Each tempera- ture was recorded once every 12 seconds on a Speedomax W multipoint recorder (Leeds and Northrup, Model AZAR-H). The calibration curve for the thermocouples is presented in Appendix 1. Respiratory rate was monitored by a mercury—in—rubber strain gauge stretched around the thorax, and a Model 270 plethysmograph (Parks Electronics Laboratory, Beaverton, Oregon). The output of the plethysmograph was recorded on a Grass polygraph (Model 7WC12PA Ink-Writing Oscillograph). Blood samples were drawn through a 40—cm length of poly- ethylene tubing (Intramedic 60: i.d. .030 inch; Clay Adams) connected by an adaptor to the stopcock affixed to the cat's skull. l was withd blood was which was syringe be Menthal (1 Sta-‘5 ““1“; bod L .15“. “S (1966) (up: a« S 6 8 . 4 an 552 37 skull. The stagnant fluid in cannula, adaptor, and stopcock was withdrawn and discarded, and a 2-3 cc sample of arterial blood was drawn into a 10 cc glass syringe, the deadspace of which was filled with 1% heparin. The back end of the syringe barrel was coated with stopcock grease (Dow Corning) and the syringe was stoppered with a mercury—filled cap. Samples were stored in ice water until analysis, which oc- curred not more than six hours after the sample was drawn. Blood pH was determined with a glass electrode (Type e5021a, Radiometer, Copenhagen, Denmark) and pH meter (PHM 27, Radiometer). PCO of the blood was determined with a 2 type E5036 P electrode and a type PHA927b gas monitor CO2 (Radiometer). P0 was determined with a type E5046 electrode 2 and the PHA927b gas monitor (Radiometer). All electrodes were thermostatted to 38-39.5°C (thermostat temperature was recorded during each analysis period). pH values were cor- rected to the appropriate rectal temperature by the factor of Rosenthal (1948) and gas tensions were corrected to corre- sponding body temperature using the factors given by Severing- haus (1966). The pH electrode was calibrated with two buffers (pH's 6.84 and 7.384; Instrumentation Lab. Inc., Lexington, Mass., 02173). The PCO electrode was calibrated using ali- 2 quots from two distilled water reservoirs, each of which had been equilibrated with one of two gases of known CO2 content (analysis performed on a Haldane apparatus). The P0 elec- 2 trode was calibrated using an oxygen-free solution (5 ml of 0.01 M 1301 Copenhagen Barometric Scientific ‘0 ‘ 55:: P3‘ . 5 Which St h’Eve C ‘ ons' \ l e}- «e 551:6? «e enOUC d 4« “Cd. I; a: _ ex ~“e, th e d . at \JQSQ 38 0.01 M Borax solution and 100 mg sodium sulfite; Radiometer, Copenhagen), and distilled water equilibrated with air. Barometric pressure was read on a mercury barometer (Welch Scientific Co., Skokie, 111.). 7. Experimental design Animals were exposed to ambient temperatures of 32.0, 35.0, 36.5, 38.0, 39.5, and 41.03C. Data collection began after an exposure of not less than 90 minutes, when the cat reached a thermal steady state (skin, hypothalamic, and rectal temperatures and respiratory frequency stable for 30 minutes). A 3 cc blood sample was drawn, and readings of ambient, rectal, skin and hypothalamic temperatures, and respiratory frequency were taken every 5 minutes for a 30 minute period. A second, 2 cc blood sample was then drawn. In some cases readings were continued for another 30 minute period and a third, 2 cc blood sample was drawn. During the experiments, the cats were observed carefully to determine whether they rested quietly or struggled. Those cats which struggled (violent movements of the legs and trunk) were considered "exercising animals". If the exercise was severe enough to increase rectal temperature the data were dis- carded. If exercise occurred with no change in rectal temper- ature, the data were retained but analyzed separately from those obtained from resting animals. a Calcuj Aver the temps tional co area: T 39 8. Calculations Average skin temperature was calculated by weighting the temperature of each skin site according to the propor- tional contribution of that region to the total body surface area: TS = Tear (0.034) + Thead (0.110) + Tforefoot (0.066) . + . . . + Tchest (0 405) ¢upper hind leg (0 221) + Tlower hind leg (0.113) + Ttail (0.051). Proportioning constants for the various skin sites are derived from Vaughan and Adams (1967). Bicarbonate concentration of arterial blood, in milli- equivalents per liter, was calculated from the following equation: 0 ) log [HCOS] = pH - pK' + log (aP C 2 where pK' and a (the solubility constant for CO in plasma) 2 were adjusted according to the appropriate rectal temperature (Severinghaus, 1965). 9. Analysis of data For all temperatures and respiratory frequency, each point on the graphs (Figures 5-9 and Appendices 2-5) repre— sents the mean of seven measurements taken at 5-minute inter- vals during a thermal steady state. For blood gas tensions and pH (Figures 10-13 and Appendices 6-16), each point repre- sents the mean of at least 2 determinations on a single blood sample. PaCO values from experiments in which the PCO of 2 2 initial and final blood samples differed by more than 3 mm Hg were excluded from all analyses. For a variable, « statistica frequency were exclu: aethod of Presence 0; tiODShips 1 40 For all graphs in which temperature is the dependent variable, data from exercising animals were included in the statistical analyses. For graphs in which respiratory frequency is the dependent variable, data from exercising cats were excluded. All straight lines were calculated by the method of least squares; the F test was used to detect the presence of significant non-linearity. All non—linear rela— tionships were fitted by eye. RESULTS Data presented in Table 1 and Figures 5 and 6 indicate that the thermoregulatory activity of the cats used in this study conformed to the pattern previously established as characteristic for this Species (Adams et 21,, 1970; see Discussion). The means and standard errors of body tempera- tures and respiratory frequency in each 30-minute steady— state measurement period are presented in Table 1. During steady-state adjustments to ambient temperatures between 32 and 42°C, unanesthetized cats maintained rectal temperature at successively higher levels, as shown in Figure 5. An alternative analysis suggests that the rectal tempera- ture increases linearly only at ambient temperatures above 34°C. Over the ambient temperature range from 32 to 42°C, average skin temperature increased linearly with increasing ambient temperature, as shown in Figure 6. In Appendix 2, average skin temperature is plotted against rectal tempera- ture, of which it appears to be a linear function. The rela— tionship of average skin temperature to hypothalamic tempera- ture, shown in Appendix 3, is less well defined than the .relationship to rectal temperature shown in Appendix 2, 41 Means and . (in °C) an: cats in all x \— Cat Run NO. No . —.______ (A) LA) l l l l l 1 3 3 3 3 3 3 3 3 3 5 a: 42 TABLE 1 Means and standard errors of body and ambient temperatures (in °C) and respiratory frequency (in breaths/min) of all cats in all experiments. 39.81.01 s2? :2: -Ta Tre Ts Thy f 1 2 32.0i.10 39.11.08 36.61.04 38.61.08 181 0 1 3 35.01.10 39.41.09 37.41.08 38.91.02 211 l 1 4 35.11.05 40.01.00 38.21.02 39.41.00 341 3 1 5 38.01.01 40.41.00 39.01.09 39.41.10 215110 1 6 38.21.09 40.51.01 ' 39.11.06 39.51.03 2441 5 l 7 41.21.06 41.01.04 40.51.02 40.11.01 2521 3 3 1* 32.01.08 39.31.04 37.01.05 39.11.03 411 1 3 2 35.01.04 39.51.02 38.11.04 39.61.01 371 3 . 3 3 35.11.07 39.31.02 37.41.01 39.11.04 511 l 3 4 36.61.04. 39.41.02 38.21.02 39.41.03 581 2 3 5 38.01.03 40.41.02 39.71.03 39.81.01 1161 5 3 6 37.91.03 40.01.00 39.51.01 38.91.09 1331 8 3 7 39.11.03 40.41.01 39.91.02 39.91.02 1341 4 3 8* 41.01.03 40.71.05 40.31.03 39.91.04 1331 3 3 9 41.01.10 40.81.01 40.41.02 40.11.04 2051 3 5 1 32.41.05 39.61.02 36.61.03 39.51.02 371 3 6 1 32.01.03 39.41.03 37.01.03 39.51.05 391 4 6 2 33.11.05 39.41.02 37.21.04 39.41.02 611 5 6 3 36.41.05 40.11.02 38.81.02 40.31.08 841 5 6 4* 41.11.08 40.11.01 40.21.06 1521 9 *indicates exercising animal 43 me. New .Aao>oa Ho.ov o Eoum uconMMHU mauGMOHMHcmflm ma omoam one .Hma.o u mna.o u omon so Hm>uou:H mocooflmsoo wmm .mw.o u H “¢.mm + we NmH.o n was .mamfiflcm msflumwn Ham Mom .mumo msflmfloumxm wumsmflmmo mmaonflo ammo «mamawcm mcflummu oumoflpcw upon pflaom .Ammmflomgm “we “Dov musumummfimu usmflnfim mo coauocsm o no csonm mH Amumcflouo “one “Dov ousumummfimu Hmuoom .ousumuomfiou usoHnEm mo coapossm n no onsumuomaou Hmuoom .m ousmflm 44 N¢ 0..» mm m wusmflm mm 9mm ndm 0.0 w 0 dc 04¢ 0.. ¢ 45 WSW .mes.o I osm.o "macaw m co Hm>umucn monogamcoo wmm .mm.o u H 1H.mm + a mme.o u we .mumo msflmflonoxo oumamflmop moaonflo ammo «mHmEHsm mcflummu mumoflosfl m muop pflaom .Ammmflomnm x B “Dov ousumummawu usmflnfim mo cofiuocsw m mm s3onm mH Aopmaflpuo «m9 “Dov ousumuomfiou afixm ommuo>4 .ousumquEop ucmflnam mo GOHHOQDM m mm ousumuomfiou sflxm oomuo>¢ .m ousmflm \ v 46 N¢ O¢ mm m whamwm mm mm hm mm mm 0? _ v probably b ature from (see below The re temperature Figure 7. the cats we Ship betWee exceeded 39 reCtal to h The re rectal: and in Pigllres Prev10usly 1966)‘ Fre temperatUre timeshold v TQCtal temp 47 probably because of the dissociation of hypothalamic temper- ature from other deep body temperatures in panting animals (see below and Discussion). The relationships of rectal temperature to hypothelamic temperature during thermal steady states are presented in Figure 7. At low rectal and hypothalamic temperatures (when the cats were not panting) there existed a linear relation- ship between the two temperatures. When rectal temperature exceeded 39.6°C, and panting occurred, the relationship of rectal to hypothalamic temperature was still linear, but the slope was steeper. The relationships of reSpiratory frequency to ambient, rectal, and hypothalamic temperatures, respectively, shown in Figures 8 and 9 and Appendix 4, also conform to the pattern previously established (Adams gg‘al., 1970; Hunter and Adams, 1966). Frequency was relatively independent of ambient temperature when the temperature was below 36°C, but above this threshold value frequency rose with increasing ambient temper- ature (Figure 8). The existence of a threshold value for rectal temperature is not well established, since the correla- tion coefficient for frequency as a function of rectal temper- ature when rectal temperature is greater than 39.5°C is 0.87, compared to r = 0.89 for frequency as a function of rectal temperature when rectal temperature is above 39.0°C (Figure 9). The linear correlation of frequency with hypothalamic temper- ature was not strong (r = 0.52, Appendix 4). The higher 48 .oo.a I «v.0 macaw co Hm>uoucfl mocmpflmsoo wmm .mm.o n H “H.o I mne mo.H u one .Ooh.mm m>onm mmucumuomEou Hmuoou mom .me.o . ea.o u macaw so Hm>uauaH monoeflmcoo wmm .mm.o u n “H.vm + mne mm.o u one .Oo>.mm 30Hon mmusumuomEou Hmuoou Mom .mumo mcflmflouoxm oum0flpcfl moaonflo some “mamaflcm mcflumou mumsmflmmp we muoo pflaom .Ammmfiomnm a 9 “Dev ousumuomfiou OHEmamcuommn mo on coauocsw m mm czonm ma AouMCHpHo n 9 “00V musumuomfimp Hmuoom .ousumnomfimu anmamcpommn mo cofluUCSM m we ouswmuomew Hmuomm .h musmflm 49 h musmwm 0.0 m .m 0.0m Own 0.0 ¢ 00¢ 0.. ¢ 50 .m.mm I v.m u omon so Hm>uoucH monopflmsoo wmo .Hm.o u H “mom I we 0.0m n m .Oomm o>onm monsumuomfiop pcoflnfim Mom .mpmo mcflpmou opmcmflmop whom UHHOm "mamsflcm mcflmwouoxm oumofiocfl moHoHHo ammo .Ammmfiomnm “we “Dov ousumuomfiou ucoHQEm mo coauocsw n no csocm ma Amandapuo “CHE\m£umoun “my wocoswoum anoumuflmmmm .musumuomfiou ucmflQEm mo cowpocsm n ma hocmsvmuw muoumuammmm .w musmflm 51 N¢ 0? mm m mhsmflm 0m V» 00 00. On. 00m 00m 52 .v.mma I m.mm H wmoam so Hm>noucfl oosmpflmcoo wmm .mm.o H H momma I one o.vma u m .haco mHmEHcm ocflumou mom .mumo mcflmfloumxo oumcmflmmo moaouflo ammo «mHmEHcm msflumon opmoflpcw on m00© Uflaom .Ammmflomnm “ a “Dov onsummmmEmu Hmuoou wo cowuocsm o no csonm mH Aoumcflono “CHE\wcumomQ “my wocmswmum >H0bmuflmmom .ousumuomamp Hmuomh Mo GOHpocsm o no hocmsvoum WHODMHHQmmm .m musmflm 53 0.. v I ihflflr 00¢ a musmfim 00¢ on 00. 00. 00m 00m 54 correlation of frequency with rectal temperature than with hypothalamic temperature suggests that hypothalamic tempera- ture is not the primary drive for the respiratory response to heat stress in the unanesthetized cat (see Discussion). The correlation coefficient for respiratory frequency as a function of average skin temperature is 0.38 (Appendix 5). The effect of polypnea and panting on the pH and gas content of the blood are shown in Table 2 and Figures 10—12. Table 2 contains means and standard errors of pH and blood gas tensions, and means of bicarbonate concentration for all blood samples. All data are derived from steady-state blood samples drawn after a minimum of 90 minutes exposure to a given ambient temperature. The steady-state levels of PaCO 2 during exposure to various ambient temperatures are shown as a function of respiratory frequency in Figure 10. The curve is nonlinear at the 0.01 level, and is not a simple exponential function. PaCO declined most steeply as frequency rose from 2 20/min to 50/min. Above this frequency (ca. SO/min) PaCO 2 continued to decrease as frequency rose, although less steeply than at low frequencies. The relationships of arterial blood carbon dioxide tension to ambient and body temperatures are shown in Appendices 6-9. All of these relationships of PaCO 2 to temperature are believed to be a consequence of the rela- tionship of PaCO to frequency and the dependence of frequency 2 on the various temperatures (Figures 8 and 9 and Appendices 4-5). Mean values and standard errors of blood gas tensions, 55 TABLE 2 and pH and means of bicarbonate concentration for all cats in all experiments. Cat Run Sam- PaC02 H Paoz [Hcog] No. No. ple (mmHg) p (mmHg) (mEg/lO 1 2 1 42.41L .2 7.386i .003 "“ 24.5 2 43.6i .4 7.358: .003 —-~— 23.6 1 3 l ---- 7.370i .000 -——- -—-- 2 ---- 7.3381 .004 ---- ---— 1 4 1 41. 0+ .0 7.338i .009 --~- 21.3 2 40. 1+1. 4 7.338i .008 —--- 20.6 1 5 1 ---- 7.377i .006 ---- ---- 2 ---- 7.374i .002 ---- ---- 1 6 1 39.21 .4 7.334: .002 ---- 19.8 2 32.01 .7 7.3841 .002 ---- 18.4 1 7 1 29.4i .0 7.419i .001 116.210. 8 18.1 2 25.61 .4 7.436: .002 113. 810. 0 16.6 3 1* 1 733.91 .7 7.3651 .003 108. 310. 4 18.6 2 37.51 .6 7.2281 .010 116. 010.4 14.9 3 2 1 36.71 .0 7.3841 .004 115. 810.0 21.0 3 3 1 33.21 .4 7.4181 .001 109. 410.1 20.8 2 31.61 .2 7.4141 .002 117. 410. 5 19.5 3 4 1 33:0i .4 7.4351 .001 115. 010.7 21.4 2 34.0i .6 7.4141 .005 116. 010. 0 21.0 3 5 l 31.3i .6 7.4151 .005 116.410. 5 19.3 2 27.4i .3 7.3161 .004 122. 610. 9 13.4 3 6 1 34.01 .2 7.3801 .000 111. 810. 4 19.2 2 33.91 .5 7.3761 .004 112.011.4 19.0 3 7 1 35.51 .5 7.4091 .003 ll6.811.5 21.6 2 34.21 .2 7.4151 .000 116.710.6 21.0 3 35.81 .2 7.3861 .006 110.1.10. 5 20.6 3 8* 1 32.01 .3 7.3351 .007 91.711.7 16.2 2 30.21 .6 7.3911 .004 96. 010. 2 17.5 3 9 l 29.21 .0 7.4201 .002 115.111. 0 18.1 2 28.11 .1 7.4051 .004 123. 710. 6 16.8 5 1 1 34.91 .6 7.3881 .005 98. 010. 5 20.2 2 30.41 .2 7.3981 .005 101. 610. 9 18.0 6 1 1 36.81 .0 7.3601 .000 90.111.5 19.9 6 2 l 38.81 .0 7.3291 .008 99.810.8 19.6 6 3 1 32.81 .2 7.3641 .005 121. 811.2 18.0 2 36.51 .4 7.3541 .000 126. 211. 4 19.4 6 4* 1 39.51 .9 7.3101 .000 90. 711. 4 18.8 2 37.11 .1 7.3181 .006 102. 810. 2 18.0 M *indicates exercising animal 56 .Aommflownm “CHE\mnumouQ “WV >ocosoomm wuoumufimmmn wo COADOCSM n no csocm ma Amumcflpuo “mm EE “mouomv coflwsou coexOAU conmmo pooan Hmflumun< N .wocosvoum muouwuflmmou mo cofluoccw m mm 00mm .oa musmflm 57 ca mHsmwm 00_ mm 58 The develOpment of hypocapnia produced no severe alka— losis, as shown in Figures 11 and 12. There was no dependence of arterial blood pH on respiratory frequency (Figure 11), nor on ambient or body temperatures (Appendices 10—12). Nevertheless, there was a linear increase of pH with decreas- ing PaCO (Figure 12), although the correlation coefficient 2 was not high (r = -0.72). As shown also in Figure 12, the calculated bicarbonate concentration of the blood fell with decreasing PaCO . Although the correlation coefficient for a 2 linear dependence of bicarbonate concentration on PaCO is 2 -0.78, the distribution of the data also suggests a sigmoid curve, with bicarbonate concentration stable when PaCO is 2 between 32 and 40 mm Hg. The changes in Pao during heat stress in the unanesthe- 2 tized cat are shown in Figure 13. At low respiratory fre— quencies, Pa rose steeply as a function of increasing 0 2 frequency. When frequency exceeded 50/min, PaO was stable 2 and maximum in resting cats. Exercising animals consistently maintained lower arterial blood oxygen tensions at high respiratory frequencies. Relationships of PaO to ambient and 2 body temperatures are presented in Appendices 13-16. Figure 14 is a record of reSpiratory movements from one cat (No. 7) exposed to 38°C. The animal was panting steadily; the mouth was always open. Cyclic variations in frequency are evident, and oscillations in the amplitude of the excursions are also present. 59 .Ammmflomnc “CHE\m£ucmHQ “my mocmscouw muoucnemmmn mo cofluocsm c we csonm we Ampccflouov mm pooHn Hmaumpufi .wososconm wuoumuflmmmu mo cofluocsM m mm mm .HH wusmflm 6O 00m 1I1Jl__.l_l1|1|]|_|_l1._l_l._l1l]l.l] a. 00m Om. Ha whamam 1..) ‘W... 00. on d d 4 mIJ1lJ ONN nNN on N and. 0 Wk owe. 61 .mmv.o I nma.o n omon co ac>uoucfl mococfimcoo wmm .mn.o u H "m.m + comm mmm.o n coaumuucoocoo mumconumoflm .Hmoo.ou I smoo.mu n mooam co Hm>nmuca oncogencoo wmm N .me.ou u u imam.» + comm smoo.on u we .Ammmeomnm “mm as a Gummy coflmcop ocflxoflc conmmo UOOHQ Hcfluopuc mo mcofiuocsm mm csocm one Aouccflouo ucmflu “moaouflo ammo “H\cmev cowumnucoocoo oucconucoflb can Aouccflouo uwma “muoc UHHOmV mm UOOHQ acflumuu< N .muco mcflummn 2H 00mm mo mCOHuUQSM no mCOHchucoocoo mDMGOQHMOHQ camcam can mm .NH mesons 62 0... ON: NNr VNI ON—u NH madman O moors. mm on mm 3.... a Cu N am N ONN nnN 0¢N mVN 63 .mHmEflcm mcflmflouoxo ouccmflmop moaouwo Como “memo mcflumou oucOHccH mpop cwaom .Acmmfiomnm “afiE\mnucoun “mv mocmsvoum wuoucnfimmmu mo cofiuocsw n no czonm ma m. Amumcflcuo “mm as u DNmV vocab amenmuuc mo scamcou com>xo N .mocmswoum MHoumuflmmoH mo coauocsm c mm 0cm .ma mesons 64 ma ousmwm 00m 00m 00. 00. on 0 alld drlfi d u - I. 1r.‘ 1 - I. -. qu a d J 1. .II-Iill1l4IJ1IJ Avmw . L .. 00 Au .0 o 1 00. .0 AV nu o .. 0: 0 0. .0 IL, 0 O O 9 .. ON. .0 .0 o No on: On. £1,925 !' Figure 14. 65 Record of respiratory movements from a singlja cat. Record of respiratory movements from a single; unanesthetized cat exposed to an ambient temperature of 38°C. 66 I . w l o .— Q . ' 'I. l I." I 4. 1 I . . I. I . .II I . . l. .. . _ c ‘I . . ' L _ If “I! . II . F _ ¢ 1 . q. I V II' . II . . _ IIIII.’ . n U . . Ii .I!IJ_IIiI . . _ .. . I. I--rII, .. I . . I. I _ . , ‘1 _ . . I u..!.. .1 fi. _ .I \. . . ‘ . x . a _ V . ” II II. ‘. 3055c .— _ . . .. A . A ... . i4 . W I w A . I- I. .. a a ”“1 . ‘I..‘. ‘I . .I--IIJI. - - . . . w 1}. wsT.IIF m -- . H--_ w “W. .Ir.\ 1 1 M .7: - - nu. . If. u _ IVA Figure 14 DISCUSSION A homeotherm, by definition, is capable of maintaining a relatively constant deep body temperature despite moderate changes in the thermal properties of its environment. When exposed to a mild heat stress, the animal may employ conduc— tive, convective, and radiant heat transfer (collectively . Li referred to as "dry" heat exchange) as well as evaporative heat loss to dissipate the heat produced by metabolism in its tissues. Since each of these three forms of dry heat exchange depends upon the temperature gradient from the animal's body surface to the environment, and upon the body surface area available for heat exchange, a homeotherm can modulate its dry heat exchange by controlling the temperature of those portions of its body which have large surface area- to-volume ratios. Such alterations in body surface tempera- ture are due primarily to changes in cutaneous blood flow. Selective cutaneous vasomotion in response to mild and moderate heat stress has been demonstrated in the unanes— thetized cat (Adams 33 al., 1970) and is confirmed by the data presented here (Figure 6). Average skin temperature increased linearly as ambient temperature rose from 32°C to 42°C, and therefore the increase in dry heat loss begins at ambient 67 68 temperatures just above the thermoneutral zone (26-32°C; Adams gt al., 1970). The linear relationship also suggests that dry heat loss can be graded for a response prOportional to the levels of thermal stress. In addition to augmenting heat loss by increasing skin temperature, the homeotherm may store heat, thereby changing the temperature of its tissues and its total body heat con- tent. The storage must be limited if the animal is to remain homeothermic, but such retention of heat may result in a con- siderable saving of water. Data presented in Figure 5 con- firm the previous report (Adams 33 al., 1970) that unanesthe- tized cats tolerate a substantial increase in deep body temperature during severe heat stress, and Figure 9 presents evidence that maximum respiratory frequency is not evoked unless deep body temperature is raised. As ambient temperature rises, dry heat loss declines due to the reduction in the temperature gradient between body surface and environment. Evaporative heat loss must rise to compensate for the reduced dry heat loss if homeothermy is to be maintained. Evaporative cooling in a furred homeotherm is essentially restricted to the upper respiratory tract, and an increase in evaporative heat loss without a large rise in body temperature implies augmented air movement over these evaporative surfaces. Such an increase in total air movement can be brought about by elevating either respiratory frequency or tidal volume, or both. Figures 8 and 9 and Appendices 4 69 and 5 present evidence that respiratory frequency of the un- anesthetized cat rose as ambient and body temperatures increased. The rise in frequency began when ambient tempera— ture exceeded 35.5°C, and respiratory frequency rose linearly with ambient temperatures above 35.5°C (Figure 8). Mild exercise resulted in a lower respiratory frequency at a given ambient (Figure 8) or rectal temperature (Figure 9). The evaporative heat loss from the upper respiratory tract results in cooling of the epithelial linings of the upper pharynx and roof of the buccal cavity. These membranes are only a few millimeters from the base of the brain in the cat (Figure 3), and the localized cooling of the upper respiratory tract strongly influences the relationship of hypothalamic temperature to other deep body temperatures (Figure 7). The onset of polypnea shifted the linear rela- tionship of rectal to hypothalamic temperature from one line to another with a steeper slope. The presumed increase in heat loss from the upper respiratory passages as a consequence of panting tended to maintain hypothalamic temperature even further below rectal temperature than it is in thermoneutral or warm exposures, when panting does not occur. This selec- tive cooling of the lower brain areas implies that during heat stress the cat can reduce its thermoregulatory effort, increase heat storage and allow deep body temperatures to rise without developing high brain temperatures. This effect is even more strikingly demonstrated by some desert—dwelling antelOpes (Taylor, 1969). — mt. r "h ‘ ‘ I" 7O Mild exercise, which resulted in a lower respiratory frequency at a given ambient temperature (Figure 8) did not appear to affect the relationship of hypothalamic to rectal temperature during heat stress (Figure 7). This suggests that the decreased reSpiratory frequency during exercise was accompanied by an increased tidal volume so that total air movement over the upper respiratory surfaces, and total heat loss from those surfaces, was similar to that of the resting animal under analogous exposure conditions. Respiratory frequency was better predicted by rectal and ambient temperatures than by hypothalamic temperature or average skin temperature (Figures 8 and 9, and Appendices 4 and 5). This suggests that the temperature of the thermo— sensible cells in the anterior hypothalamus (where hypothal— amic temperature was measured in this study) is not the primary input driving the respiratory response to heat stress. This hypothesis is further supported by observations on cats during the transition from polypnea to panting as the animal approached the steady state. Rectal and hypothalamic temperatures rose in parallel during polypnea (Figure 7). When panting began, hypothalamic temperature stabilized or sometimes fell, while rectal temperature continued to rise, later to stabilize at a higher value. Respiratory frequency never declined when hypothalamic temperature fell if rectal temperature was still rising. 71 Forster and Ferguson (1952) reported two separate pat- terns for the initiation of panting in unanesthetized cats. One group of cats began to pant when ambient and skin tem- peratures rose, with no rise in rectal temperature ("reflex "m .n-a I! I panters"); the other group began to pant only when deep body ———v temperature rose ("central panters"). Data points at f = 215 and f = 244, which lie to the left of the data grouping in Figures 8 and 9, were recorded from a single cat (No. 1). We. -. ' i This animal increased its respiratory frequency more steeply with increasing temperature than did the other cats. It is possible that this animal was a "reflex panter"; the other cats would then have been "central panters". Alternatively, at the initiation of panting the one cat (No. 1) may have shifted abruptly to a respiratory frequency near the resonant, frequency of its thorax, as reported in dogs (Crawford, 1962), while the other cats showed a more gradual increase in fre- quency. Further, the unevaluated influence of the animal's previous experience with high ambient temperatures may play a role. Possibly cat No. 1 had experienced severe heat stress before this exposure and its response patterns were better established than those of the other cats. The onset of panting in all cats conformed to the pattern described by Hemingway (1938) and Albers (1961a) for dogs and by Ingram and Legge (1970) for pigs; that is, short bouts of panting interrupted the polypnea at gradually decreasing inter- vals. Also, the animals became increasingly restless as 72 respiratory frequency rose during the period of polypnea, and the animals' apparent discomfort disappeared when panting began (see Hemingway, 1938, regarding similar responses by dogs). Shortly before the initiation of panting the cats began to lick their noses frequently, and also licked the restraining frame. "Phase II" breathing, defined as a decrease in respira- tory frequency with a concomitant increase in tidal volume during very severe heat stress (Bianca, 1958), was never observed in this study. In preliminary experiments, cats which were exposed to 41°C ambient temperature develOped rectal temperatures as high as 4l.8°C without exhibiting the Phase II pattern. The failure to observe Phase II breathing in these experiments is judged not to be due to an insuf- ficiently high rectal temperature and Phase II breathing does not appear to be a characteristic hyperthermic response of unanesthetized cats. The increase in respiratory frequency in response to heat stress in the unanesthetized cat serves to increase the total air flow over the upper respiratory passages and facili- tates heat loss by evaporation (Adams 33 al., 1970). However, were air movement over alveolar surfaces also increased, hypocapnia and alkalosis would ensue, adding the threat of acid-base disturbances to that of the thermal stress. Elevation in respiratory frequency might, of course, be countered by decreased tidal volume, as has been reported in 73 the unanesthetized ox, sheep, goat, pig, and dog (see Review of the Literature). In the ox (Hales and Findlay, l968a), sheep (Hales 23 al., 1970), and dog (Albers, 1961a) such compensation is sufficient to prevent hypocapnia and alkalosis until respiratory frequency reaches its maximum value. In ‘_§‘ M ~—— the goat, hypocapnia and alkalosis develOp despite the reduced tidal volume (Heisey et al., 1971). The responses of the unanesthetized cat do not conform g,- to either the pattern reported for the dog (no alkalosis or ' E; hypocapnia) or that observed in the goat (severe hypocapnia with alkalosis), since cats developed hypocapnia (PaCO falling from 43 mm Hg to 33 mm Hg) at low respiratory fre- quencies (below 50/min), but failed to exhibit severe al- kalosis even at respiratory frequencies up to ZOO/min (Figures 11 and 12). The decrease in PaCOZ with rising respiratory frequency is quite steep at frequencies below 50/min (10 mm Hg drop in Paco2 as frequency rises from 18 to SO/min), which suggests that at respiratory frequencies below SO/min the unanesthetized cat fails to compensate for the increased respiratory frequency with a decrease in tidal volume, and hyperventilation results. At respiratory frequencies above 50/min, the decline of Pa continued, but was considerably CO2 less steep (5 mm Hg decline with an increase of lSO/min in frequency), suggesting that the cat compensates relatively more effectively for large increases in respiratory frequency. A/_j 74 These data are consistent with those of von Euler et al. (1970), who reported that, as body temperature of decerebrate cats increased from thermoneutral levels to values just below the threshold for panting, minute ventilation increased due to elevations in both tidal volume and frequency. The Vii—.29 greater the increase in temperature, the larger was the con- tribution of respiratory frequency to the total increase in ventilation. Albers (1961a) also observed that the ratio of - r__— ‘ l 5‘. I deadspace ix) tidal volume rose as frequency increased during panting in the dog. In a resting animal at thermoneutral ambient temperature, alveolar ventilation is strictly regulated by the PCO2 of the interstitial fluid (and inferentially the intracellular pH) in the region of the medullary respiratory control centers (Leusen, 1972). The hypocapnia exhibited by the cats in this study (PaCOZ decreasing from 43 mm Hg to 29 mm Hg; Figure 10) should be a potent inhibitor of ventilation if present under thermoneutral conditions. Not only would the decreased PCO2 of the blood perfusing the carotid and aortic bodies be inhibitory to ventilation (Gray, 1968), but sys- temic hypocapnia results in a loss of CO2 from the cerebro- spinal fluid and a rise in CSF pH (Kazemi 33 al., 1967). Since the interstitial fluid bathing the chemosensitive areas of the medulla oblongata is in contact with both blood and CSF, carbon dioxide tension near the medullary chemoreceptors should fall, and intracellular pH should rise. That the 75 reduced chemoreceptor drive from both central and peripheral receptors fails to inhibit respiration during thermal panting in the cat implies that fundamental modifications of the respiratory control system have occurred. Albers (1961c) found that the threshold for increased ventilation in response to CO2 inhalation was decreased dur— ing panting, although the slope of the alveolar ventilation-— PaCO reSponse curve was unchanged. The patterns of the 2 response to CO during normothermia and hyperthermia differed 2 significantly. If respiratory frequency was initially low, it rose when Paco increased. If frequency was initially 2 high due to a thermal drive, it fell when CO2 inhalation began, and the increased ventilation in response to CO2 was brought about by an elevated tidal volume. It appears, therefore, that a compromise is reached during panting so that increased respiratory evaporative heat loss and regulation against hypercapnia coexist. The decreased threshold for the CO response curve permits panting to continue despite a 2 degree of hypocapnia which would otherwise be inhibitory to respiratory frequency. If hypercapnia (induced, for example, by CO inhalation) becomes a threat to homeostasis, the 2 shallow respiratory pattern of panting is modified by decreas- ing the respiratory rate and increasing tidal volume. This hypothesis also explains the lower respiratory frequencies seen during exercise in this study (Figure 8). The contracting muscles provide an internal source of CO and the response 2' 76 is a slowing and, probably, a deepening of the reSpiratory pattern (see above). Chapot (1967) suggested that hypocapnia is actually a prerequisite for panting. Using the anesthetized cat, he found that hypocapnia produced phrenic nerve discharge pat- terns very similar to those associated with thermal panting. Chapot proposed that panting is normally initiated by in- creased body temperature which enhances alveolar ventilation, and the resultant decrease in Paco2 then triggers panting. The increased alveolar ventilation could result from a rise in the temperature of the carotid bodies, since Bernthal and Weeks (1939) showed that warming the blood perfusing this tissue causes an increase either in respiratory frequency or in tidal volume, or in both. Chapot's hypothesis that hypocapnia induces panting is supported by Pleschka's observations on dogs (Pleschka, 1969), in which hypocapnia induced polypnea even when body temperature was low. Von Euler 33 31., (1970) also found that, irrespective of the cause of polypnea (decortication, elec— trical stimulation of dorsal hypothalamus, thermal stimulation of ventral hypothalamus), an inverse respiratory frequency-- PaCOZ relationship resulted, paralleling the responses re- ported in Figure 10. A pronounced oscillation in respiratory frequency and tidal volume in decorticate polypneic cats breathing pure oxygen has been reported (von Euler et al., 1970). Similar '/ _ ”1 77 oscillations in respiratory frequency, and presumably in tidal volume, were observed in one panting cat in the present study (Figure 14). The Pa02 of panting cats is high (see below, and Figure 13), and the oxygen-sensitive chemoreceptors should have been "functionally denervated" in this animal, although perhaps not as completely as they were in the cat breathing oxygen. Paco values in cats resting at 32°C ambient temperature 2 (36.9-43.6 mm Hg), with reSpiratory frequency below 40/min (Figure 10 and Table 2) are higher than those reported earlier for unanesthetized cats (28-32 mm Hg; Fink and School- man, 1962; Sorensen, 1967; Herbert and Mitchell, 1971). Cats in this study were resting quietly in the restraining ham- mock, and frequently became drowsy when exposed to 32-35°C environments. The lower PaCOZ values reported previously might have resulted from emotional hyperventilation during blood sampling in the earlier studies, and from failure of the authors to adjust measured values for the effect of body temperature. In several species of homeotherms which rely on panting to combat heat stress, the hypocapnia which becomes marked at the peak of Phase I breathing is accompanied by alkalosis (ox, Bianca and Findlay, 1962; sheep, Hales et_al., 1970; goat, Heisey gt 31., 1971). However, data reported in Figure 11 reveal that no severe alkalosis occurred in the panting cat despite the existence of substantial hypocapnia. The mean ‘ '-- -—-m . I" ' '7’ 78 pH (7.384) for all cats at all ambient temperatures agrees with that (7.38) reported by Fink and Schoolman (1962) for unanesthetized cats at thermoneutral temperatures. Data reported in Figure 12, in which pH is shown as a function of P . . . . SCOZ, indicate that pH increased by less than 0.1 unit as Paco fell from 43 to 28 mm Hg. Data reported in Figures 11 aid 12, taken together, suggest that tidal volumes in panting cats are variable, since were they constant, the inverse relationship of Paco to respiratory frequency should cause pH to rise as frequenc; increases. The rise of pH with decreasing PaCOZ is not large (0.1 unit with a 15 mm Hg change in Pacoz; Figure 12). Several factors act to minimize alkalosis despite the hypocapnia: first, the buffering capacities of the plasma proteins and hemoglobin, and second, the decrease in plasma bicarbonate concentration (Figure 12). The reduction in bicarbonate concentration is larger than can be accounted for by loss of 2, even if all the CO2 which is lost (as Paco falls from control to the stable hypocapnic level) is 2 assumed to come from plasma bicarbonate stores. It is prob- biCarbonate as CO able that some of the bicarbonate is excreted by the kidneys, since Fuller and MacLeod (1956) demonstrated that renal bicarbonate excretion increases during respiratory alkalosis. Studies by Sullivan and McVaugh (1963) indicate that the . + . . effect of changes in P on renal H excretion, and infer- C02 reabsorption, is rapid. Also, Bianca (1955) entially on HCO3 79 reported that acutely heat-stressed calves excrete alkaline urine while maintaining a normal venous blood pH. Finally, lactic acid has been shown to accumulate in the blood of dogs (Frankel et 31., 1962), cattle (Hales et al., 1967), and chickens (Frankel, 1965) during thermal panting. This ?% O and oxygen saturation fittaj 2 5 (Anrep and Cannan, 1923; Frankel e3 31., 1963) and increases E accumulation is independent of P with decreasing P (Anrep and Cannan, 1923; Takano, 1968, i, v a C02 1970). Lactate has also been shown to increase in CSF . By (Granholm and Siesjo, 1969), probably as a consequence of decreased brain blood flow caused by the hypocapnia (Smith et 31., 1971). The effect of thermal panting on Pao is shown by data 2 reported in Figure 13. Pa rose steeply as respiratory 02 frequency was elevated from 20/min to 70/min. The increase in arterial oxygen tension is due to hyperventilation, as indicated by data reported in Figure 10, and also possibly to a decrease in oxygen consumption. Hales and Findley (1968b) reported a decreased oxygen consumption during moderate heat stress in the ox. At ambient temperatures of 32 and 35°C (f = 20-70/min) cats appeared relaxed and drowsy, and reduced whole body metabolic rate could be reasonably presumed. At respiratory frequencies above 70/min, the arterial oxygen tension of resting cats declined slightly as frequency rose (Figure 13). This reduction is attributed to increased oxygen extraction from arterial blood with an insufficient 80 increase in alveolar ventilation. The increased oxygen con- sumption is presumed to be due to the increase in body temperature (Van't Hoff-Arrhenius effect), and to increased work by the respiratory muscles (Hildebrandt, 1969) and the heart (Whittow, 1965). At low respiratory frequencies (below 70/min; Figure 13) the P30 of resting and exercising cats appears to be the 2 same. At respiratory frequencies exceeding 70/min, exercis- Eiw ing animals maintained arterial oxygen tensions consistently - lower than those of resting cats with the same respiratory frequency. The lower oxygen tensions in the exercising cats are believed to be due to a considerable increase in oxygen extraction from arterial blood by the somatic musculature, and possibly also the heart, without a sufficient increase in alveolar ventilation. During acute heat stress.in the unanesthetized cat, oxygen tension of arterial blood does not appear to be regulated, but appears to be the passive result of variable amounts of oxygen extraction superimposed upon thermally driven hyperentilation, at least when Pa02 exceeds 90 mm Hg. CONCLUSIONS The increase in respiratory frequency displayed by un- anesthetized cats during heat stress results in hyper- ventilation, with a decline in Paco from 43 mm Hg when 2 respiratory frequency is 18/min to 28 mm Hg at a frequency of 205/min. pH of arterial blood is not dependent on respiratory frequency, but rises 0.1 unit as PaCO falls from 43 to 2 28 mm Hg. The decline of plasma bicarbonate concentration as PaCO 2 falls helps to minimize the alkalosis in the face of hypocapnia. At respiratory frequencies below 70/min, PaO rises steeply due to the thermally induced hypervefitilation. 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