THE lNFLUENCE 0? A TRANQUILIZER,
RAUWOLHA SERPENTENA,
ON THE HEMGDYNAMICS AND
GROW?H~ 3F TEERKEYS

Thesis for "10 Degree of M. 5.
MICHEGAN STATE UNEE’EKSET?

Elwood: Wiliiiam Speckmann. It.
1959

 

 

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LIBRARY

Michigan State
University

 

THE IHFLUENCE OF A TRAHQUILIZER,
RAUWO FIA SERPEKTIIA, ON THE

HE-IODYIIAI-TICS AITD GROWTH OF TUPKEYS

Thesis for the Degree of M. S.
Michigan State University
Elwood William Speckmann, Jr.

1959

THE IUFLUEKCE OF A TRANQUILIZER, RAUWOLFIA SERPEHTIIA,

N THE HEMODYKAKICS AND GROWTH OF TURKEYS

By

Elwood Hilliam Speckmann, Jr.

H ABSTRACT

Submitted to the College of Agriculture
Michigan State University of Agriculture and
Applied Science in partial fulfillment of
the requirements for the degree of
MASTER OF SCIENCE

Department of Poultry Science

1 959

biz-{21) [d W L13?/M 3 *3

Approved

 

Elwood H. Speckmann
1

BSTRACT

The occurrence of aortic rupture in turkeys is of utmost
economic importance to turkey raisers because it has significantly
increased the mortality, especially of the older male birds, in some
flocks. The higher blood pressure exhibited by the male suggests
increased hemodynamics to be an initiating factor of the condition.

This study approached the problem from a physiological viewpoint by
employment of a hypotensive agent, Reserpine, in an effort to reduce

blood pressure in the turkey. Broad Breasted Bronze turkeys were selected
for this investigation because they exhibit a phenomenal increase in

blood pressure while growing. They also demonstrate the highest incidence
of aortic rupture of any variety of turkey.

Reserpine was demonstrated to be a physiologically active,
dietary, hypotensive agent in Broad Breasted Bronze turkeys. Short
term (4 wks.) experiments revealed that all dosage levels between 0.1 ppm.
and 4.0 ppm. Reserpine reduced blood pressure; however, levels above
0.3 ppm. Reserpine apparently became toxic as evidenced by reduced weight
gains in those lots receiving these levels. The levels of 0.1 ppm. and
0.2 ppm. Reserpine demonstrated a significant hypotensive action without
adversely affecting weight gains; in fact, a possible growth stimulation
was exhibited by these groups. A further short term experiment demonstrated
a hemodynamic reduction by Reserpine within 5-4 days following oral
administration.

Long term (9-12 wks.) experiments incorporating pure Reserpine
into the feed demonstrated no significant difference in weight gains;
however, a tendency toward increased weight gains and feed efficiency_

was exhibited by the 0.1 ppm. and 0.2 ppm. Reserpine lots. The

Elwood W. Speckmann
2
circulatory affect was a gradual reduction in blood pressure by all lots,
the magnitude of this reduction depending upon the level of Reserpine
administered. The greatest hypotensive action was produced by the highest
level of Reserpine and the greatest significant difference was observed
in males approaching sexual maturity. A slight bradycardia was also
observed. Turkeys subjected to a known stress (0.5 cc. of 1/25,000
dilution of epinephrine injected intravenously) following twelve weeks
oral administration of Reserpine demonstrated a higher percent change in
hemodynamics than did the control lots when subjected to the same stress.
The greatest change was observed in birds which had received the highest
level of Reserpine.
Although Reserpine is a tranquilizer in addition to its hypo-
tensive properties, no signs of reduced activity were noticed in any
lot. Birds receiving Reserpine did not differ externally from controls;

however, they exhibited reduced blood pressures and heart rate.

THE IHFLUENCE OF A TRANQUILIZER, RAUWOLFIA SERPERTINA,

ON THE HEMODYNAMICS AND GROWTH OF TURKEYS

By

Elwood William Speckmann, Jr.

A THESIS

Submitted to the College of Agriculture
Michigan State University of Agriculture and
Applied Science in partial fulfillment of
the requirements for the degree of

MASTER OF SCIENCE

Department of Poultry Science

1959

ACKI‘IOW LEDG ElxIEN T

The author wishes to express his most sincere appreciation
and gratitude to Dr. R. K. Ringer of the Department of Poultry Science
for his guidance, incessant assistance and encouragement throughout
the course of study and for his critical evaluation of the manuscript.

Sincere thanks and appreciation are also extended to Mr. K. G.
Rood, Technician, for his valuable suggestions and assistance in the
recording and interpretation of the blood pressure records.

The author is also indebted to Dr. H. C. Zindel, Head,
Department of Poultry Science, for his cooperation in.making funds
and facilities available for this investigation; to Dr. R. F. Johnston,
Department of Physiology and Pharmacology, for his study and recommend-
ations toward the composition of this manuscript; to Dr. Theo H. Coleman,
Department of Poultry Science, for his helpful suggestions and constructive
review of this thesis; and to the Upjohn Company, Kalamazoo, Michigan,
for supplying the tranquilizer, Reserpine.

Further acknowledgement is extended to Dr. E. A. Gibson,
Veterinary Investigation Centre, Cambridge, England, and to Dr. B. J.
McSherry, Ontario Veterinary College, Guelph, Ontario, for the use of
their pictures to illustrate the conditions of dissecting aneurysm and

aortic rupture in the turkey.

TABLE OF CORTEETS

II‘TTRODUCTIOI‘W-T o o o o o o o o o o o o o o o o o 0
REVIEW OF LITERATURE o o o o o o o o o o o o o o
A. History of Reserpine . . . . . . . . .

B. Tranquilizers in the Animal Industry .

C. Tranquilizers Applied to the Poultry Industry . . .

D. Investigation of Avian Hemodynamics and
Aneurystooooooooooooooo

OBJECTIVES . . . . . . . . . . . . . . . . . . .
GENERAL EXPERIKEETAL PROCEDURE . . . . . . . . .
A. Blood Pressure Determination . . . . .
B. Statistical Analysis . . . . . . . . .

RESULTS AED DISCUSSION . . . . . . . . . o o . o

A. Experiment10000000000000.

B. Experiment 2 . . . . . . . . . . . . .
0. Experiment 3 . . . . . . . . . . . . .
D. Experiment 4 . . . . . . . . . . . . .
E. Experiment 5 . . . . . . . . . . . . .
F. Experiment 6 . . . . . . . . . . . . .
GEEERAL DISCUSSION . . . . . . . . . . . . . . .
SUIT-LARY AIED CONCLUSIONS . . . . . . . . . . . .

LITEPATURIE CITED 0 O O O O O O O O O O O O O O 0

ii

Dissecting

O O O O O O

 

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17
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19
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II

III

IV

V

VI

VII

VIII

IX

XI

XII

XIII

Statistical analysis of hemodynamic changes and weight
gains (5-7 wks.) following two Weeks feeding of
Reserpine (age 7 WkSo). o o o o o o o o o o o O c o 9

Statistical analysis of hemodynamic changes and weight
gains (7-9 wks.) following four weeks feeding of
Reserpine (age 9 Wksc). o c c c o c c c o o o o o o 0

Statistical analysis of hemodynamic changes and weight
gains (4-6 wks.) following two weeks feeding of
Reserpine (age 6 WkSo)c o c o c o o o o c c o o c o 0

Statistical analysis of hemodynamic changes and weight
gains (6-8 wks.) following four weeks feeding of
Reserpine (age 8 WkSo). c o o o c o c o c o c o o o 0

Statistical analysis of hemodynamic changes following
two weeks feeding of Reserpine (age 8 wks.). . . . .
Statistical analysis of hemodynamic changes and weight
gains (6-10) wks. following four weeks feeding of
Reserpine (age 10 wks.). . . . . . . . . . . . . . .
Statistical analysis of weekly and total weight gains
(ginse) following feeding of Reserpine from one through
nine weeks Of age. 0 o o o c o c o c o c o o c o o 0
Statistical analysis of hemodynamic changes following
eight weeks feeding of Reserpine. . . . . . . . . . .

Statistical analysis of hemodynamic changes following
two days feeding of Reserpine (age 11 wks.). c . . .
Statistical analysis of Hemodynamic changes following
four days feeding of Reserpine (age 11 wks.). . . . .

Statistical analysis of hemodynamic changes following
two weeks feeding of Reserpine (age 11 wks.). . . . .

Statistical analysis of hemodynamic changes following
four weeks feeding of Reserpine (age 15 wks.).

Statistical analysis of hemodynamic changes following
six weeks feeding of Reserpine (age 15 wks.). . . . .

iii

PAGE

21

22

25

55

54

41

#2

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XVII

 

LIST OF TABLES
(Continued)

Statistical analysis of hemodilamic changes following
eight weeks feeding of Reserpine (age 17 wks.). . . .

Statistical analysis of hemodynamic changes following
ten weeks feeding of Reserpine (age 19 wks.). . . . .

Statistical analysis of hemodynamic changes following
twelve weeks feeding of Reserpine (age 21 wks.). . .

Statistical analysis of percent change in hemodynamics

following a given stress on birds fed Reserpine for
tl‘felve I‘leel‘CS (age 21 VJICSQ)Q c o o o o o o o o o o o o

47

FIGURE , Egg
1 Illustration of Aortic Rupture . . . . . . . . . . . . . 5
2 Illustration of Endothelial Surface of Ruptured Aorta . 4
5 Photomicrograph of Aorta Illustrating A Dissecting

Aneurysm O O 0 O O O O O O O O O O O O O O O O O O O O O 11+

INTRODUCTION

Certain tranquilizers, particularly Reserpine, a Rauwolfia
compound, have been used extensively in human.medicine for the treatment
of hypertension, hypersensitivity, and other such maladies, but have
declined recently in usage as better tranquilizing drugs have been
developed with reduced side effects. The usage of Reserpine now has
been concentrated in the animal industry with apparent success to calm
nervous animals during shipment and to decrease their activity while
on the farm, thereby obtaining a heavier gross weight. Within the
poultry industry the use of tranquilizing agents has experienced
limited success - both practically and economically speaking. Reserpine
has been used unsuccessfully in chickens but has been used effectively
in turkeys to reduce injuries caused by excitement, handling and
marketing and in the management of pheasants to reduce cannibalism.

Dissecting aneurysm.(aortic rupture), a condition sometimes
found in rapidly growing Broad Breasted and American mammouth Bronze,
and Broad Breasted White turkeys (particularly males), is causing a
growing concern among turkey breeders and farmers because it is occurring
under various systems of management in widely scattered portions of the
United States, Canada and England. A recent survey conducted by the
Poultry Science Department, Michigan State University, found this
condition to be the leading problem confronting turkey growers in
England, and it is found in 51 of the 41 states answering the questionnaire.
Most of these states occupy northern locations. The mortality due to

this problem is generally under 5 percent of the flock; however, losses

up to 20 percent have been reported. These birds die usually between
8-24 weeks of age, thus the loss is of economic significance.

Primary investigation of aortic rupture (Fig. 1 and 2) in
his country has been from the nutritional aspect; however, reports
from turkey raisers experiencing this problem indicate the highest
incidence of death occurs frequently in the morning supposedly when the
birds are jumping off the roosts or when a producer walks through a pen
and thus disturbs them, thereby causing a stress. Stress is defined
as any adverse physiological or psychological condition which prevents
the animal from reaching his maximum.genetic potentiality. In other
words, stress is any stimuli of such magnitude as to tend to disrupt
the homeostasis of the organism thereby adversely affecting weight gains
or production. Sudden excitement or normal activities such as fighting
and sexual play, which are most frequent in growing male birds reaching
sexual maturity, will also cause a stress.

The above discussion suggests the cause of aortic rupture
to be of a physiological nature, such as stress or, increased blood
pressure or, possibly, a combination of the two. High blood pressure
could cause the rupture of a blood vessel at the weakest point and with
an added stress on top of the normal pressure it is conceivable that the
blood vessel could burst open and the resulting aortic hemorrhage occur.
This asswmption has led to an investigation of the use of a tranquilizer

in both reducing stress and lowering blood pressure simultaneously.

GIBSON, E. A.. 81 DE GRUCHY. P. H.—AORTIC RUPTURE IN TURKEYS
SUBSEQUENT TO DISSECTING ANEURYSM

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REVIEW 0? LITERATURE

Children under fifteen years of age who are hypertensive
generally have an organic disease. By the age of 50, about 2.5 percent
of the population are hypertensive. This figure rises rapidly to almost
50 percent by the age of 50. After maturity it is normal for the human
blood pressure to increase approximately 1 mm. mercury each year, thus
hypertension is frequently encountered during old age. The study of
human hypertension without application of extrinsic factors requires a
considerable length of time and effort. The male turkey approaching
maturity exhibits an average increase of 10 mm. mercury per week
(Ringer and Rood, 1959), or compared with humans, ages 100 years in 10
weeks. No other animal has been demonstrated to exhibit such a phenomenal
increase or to attain such a high blood pressure within so short a
duration of time. The turkey, therefore, is an excellent animal for
the study of blood pressure and the conditions which effect hypertension.
History of Resegpine:

Iickell (1956), from his extensive work in plant physiology,
reports Rauwolfia to appear in ancient Indian literature as long as
5,000 years ago to be useful as a febrifuge and as a remedy for snake
bites and a cure for dysentery. Later, crude preparations were used to
treat insanity, insomnia, hypochondria, cholera, and as a sedative.

Schlittler (195#) reports the exploits of Leonard Rauwolf, a
German physician and botanist in the latter part of the Sixteenth Century.
Rauwolf's published work in 1582 of his expeditions to Asia and Africa
to study medicinal plants aroused considerable interest. Later, when a
new genus was added to the plant family Apocynaceae, it was called

Rauwolfia in honor of Rauwolf.

The plant is indigenous to India; however, today some_40-5O
species of Rauwolfia have been described and are grown all over the world
in tropic and semi-tropic regions. The most important specie is Rauwolfia
serpentina because of it's medicinal properties. It has been inferred
that Ghandi took Rauwolfia to sustain himself in his programs of passive
resistance (Anonymous, 1958).

The drug failed to attract much attention in this country
because of its slow action and rather ineffectualness in single doses.

As soon as successive treatments on the same patient were tried, there
was sudden excitement over Rauwolfia. Although used in Europe for over
500 years for the treatment of anxiety cases (Schlittler, 1954) it was
not until Chopra gt_gl. (1955) reported its hypotensive activity that the
hemodynamic influence of this drug was discovered. This unique obser-
vation along with the other advantages of Rauwolfia promoted much
interest in the drug; however, it was not tested in this country until
1950 by Dr. R. W. Wilkens, who was probably the first clinician in the
United States to work with the drug. His work mainly confirmed previous
works of Indian investigators.

The roots of the plant Rauwolfia serpentina have been known
for some time to contain numerous alkaloids and beneficial results from
using this root in human hypertension have been reported (Chopra and
Chakravarti, 1941; Bhatia, 1942; Chopra‘gt.gl., 1945, 1944, 1947;
Wilkens‘gt‘gl., 1951-52; and many other researchers). No one was
successful in extracting these ingredients until Siddiqui and Siddiqui
(1951) isolated the first crystalline alkaloid. Since then 14 substances

have been isolated from this root including Reserpine by Mueller 21.21-

7.

.(1952). It was then discovered that Reserpine was the active and most
potent ingredient in Rauwolfia serpentina and it was found to be solely
responsible for the sedative and hypotensive action of the root.

An extensive pharmacological study of Reserpine by Bein (1955)
has shown that it reduces blood pressure, decreases heart rate, produces
increased peristalsis, hypothermia, and has a general sedative action on
the central nervous system. It is slow in action, thus suggesting action
through the intermediary processes of the body, and is compatible with
other hypotensive agents.

Tranquiligers in the Animal Industry:

The serene effect of tranquilizers on animal metabolism has
promoted research in the animal industry in hopes that low levels of these
drugs might reduce animal activity or excitement. Thus increased feed
efficiency may be obtained by concentrating a greater share of metabolism
toward weight gain and production yet maintain normal food consumption.
Maintaining cattle at a higher level of efficiency than under normal
husbandry conditions with tranquilizers is synonymous with low level
antibiotic feeding and is certainly a boon to the field of animal science.
Tranquilizers in cattle in combination with antibiotic (terramycin) and
stilbestrol resulted in greater feed efficiency than either of these feed
additives alone or in single combination with the tranquilizer (Anonymous,
1958).

Stress definitely must be reduced to a minimum.if the greatest
economic returns are to be obtained from animals. Since tranquilizers were
demonstrated to reduce stress, their popularity has increased many fold.

Ruminants seem to be able to utilize tranquilizers in some manner in which

non-ruminants do not. Hogs and hens on sedation doses reduced their
activity but did not increase in weight gain over the previous untran-
quilized condition. In cattle and sheep, however, small amounts of
tranquilizer (5 grams per ton) added to the feed increased feed conversion
tremendously; lambs have improved feed efficiency 20 percent and cattle
10-20 percent on minute amounts of tranquilizer (Anonymous, 1958). As
a growth stimulant in ruminant feeding, tranquilizers promise great success,
Some researchers believe tranquilizers decrease intestinal motility,
thereby allowing the animal to utilize the feed more efficiently.
Welterink gt El° (1958) working with Reserpine alone in broilers, noted
no difference in intestinal absorption or weight gain; however, when in
combination with Lipamone (dienestrol diacetate) there was a highly
significant reduction in radioactive phosphorus transit from the crop when
compared to controls and the radioactive phosphorus reaching the intestine
was absorbed 44 percent faster in the treated group. The treated birds
were heavier and fatter than their controls.

Conner and Haas (1955) however, reported that Reserpine
enhances intestinal motility in the dog. Soon veterinarians began
experimenting with various tranquilizers mainly as chemical restraining
agents to soothe dangerous dogs or to calm nervous animals. More
recently tranquilizers have been used to calm.sheep during shearing,
to quiet stallions and bulls during handling, to soothe sows at farrowing
time and to increase milk flow, to increase milk flow in dairy cows, and
to quiet unruly milking cows. In beef cattle tranquilizers have been
used to increase rate of gain and feed efficiency, to reduce weight loss
due to excitement, to control shipping fever, and possibly to control.

dark cutting beef. In poultry tranquilizers have been incorporated in

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the feed to increase feed efficiency of broilers and to control flighty
birds (Anonymous, 1958). Tranquilizers have also been used in chinchillas
to reduce fur chewing (Earl, 1956), in pheasants to reduce fighting and
cannibalism (Hewitt and Reynolds, 1957), in turkeys to reduce shipment
losses (Earl §_.Eln! 1956), and in pigeons as an assay method (Earl.gt.gl.,
1955).

A study by Earl (1956) indicates that the toxicology of animals,
receiving Reserpine varies considerably. Horses are particularly
sensitive, requiring only 1.0 mg. of the drug per 1,000 pounds to
tranquilize while the effective dosage in cattle is 7.0-7.5 mg./1,000
pounds. Chinchillas are highly sensitive to Reserpine requiring only
1.0-2.0 mgms. daily to produce tranquilization, dogs and cats cannot
tolerate doses above 0.5 mg. per kgm. body weight, turkeys require about
0.2 mg. per kgm. body weight, and rate can tolerate doses up to 8.0 mg.
per kgm. body weight with somnolence and relatively few deaths (Plummer
93 31., 1955). One can easily see that animals vary considerably as to
dosage required to produce a threshold effect and that doses are not
necessarily dependent upon body weight.

Tranquilizers applied to the Poultry Industry:

fith the seemingly ineffective results obtained in birds, very
little actual research has been conducted in the use of tranquilizers as
an additive to poultry feeds. The effect of meprobamate on mammals has
been described by Berger (1956). His work was extended into the poultry
industry by Babcock and Taylor (1957) as they demonstrated that meprobamate
when fed to White Leghorn cockerels even at high levels (0.5 percent and
above) produced no visible effect other than growth inhibition. Garren

and Hill (1957) fed meprobamate and promazine to Leghorns at levels of

10.

275 and 550 ppm. (125 and 250 mg. per pound body weight). They found
these drugs to be ineffective in calming the birds but toxic as evidenced
by weight losses. Recent research by Sturkie‘gt.gl. (1958) established
the tranquilizing dosage level of Reserpine to be 0.1-0.2 mg. per kgm.
body weight when injected intravenously to White Leghorn capons. The
general effects of Reserpine were similar in birds and mammals however
the chicken is more sensitive to changes in heart rate and blood pressure
and requires larger doses for sedation than some other species. A
preliminary investigation by Johnston and Korkis (1959) reveals better
weight gains in broilers when Styramate was incorporated into the feed

at levels equivalent to 21 mg., 45 mg., and 86 mg. per kgm. of body
weight. The lot fed 21 mg. per kgm. body weight demonstrated the highest
weight gain through a better feed conversion from one to five weeks of age.

A study by Rood.gt‘gl. (1958) on broiler chicks (4-11 weeks),
feeding Reserpine and phenobarbital as a comparative compound, showed no
significant differences in weight gain, feed conversion, hemodynamics,
radiophosphorus uptake, specific organ weights, comb, and abdominal fat
weight, and gonadotrophin content of the pituitary, at levels equivalent
to, and 10 times, the human dosage on a body weight basis. In an activity
cage, chickens fed high levels of other tranquilizers were observed to
exhibit reduced physical activity indicating a degree of tranquilization
which might conserve energy for added body growth or increased egg
production (Ratner and Ringer, 1959).

Hewitt and Reynolds (1957) fed 5 ppm. of Reserpine to pheasants
and found that feather picking and cannibalistic tendencies were reduced
but the rate of weight gain was reduced also. Carlson (1956) feeding
Reserpine to turkeys at levels equivalent to 0.5 and 1.0 ppm. observed less
fighting in mixed groups of toms and hens but also experienced a reduction

in weight gains.

11.

Meprobamate has been found to prevent the psychological attachment
of the newly hatched duckling to the first moving object (Anonymous, 1957).

‘Chlorpromazine and Reserpine have been demonstrated to exert a
hypothermic action in mammals in addition to their tranquilizing
potentialities (Martin and Beck, 1956; Plummet gtugl., 1955; and Earl,
1956). VanMatre gtflgl. (1957) and Burger gt_gl. (1957) demonstrated a
significant protection against heat stress (115°F.) in the hen house when
feeding these drugs to chickens olderthan 4 weeks of age. Birds receiving
Reserpine suffered only a 5 percent mortality while those birds receiving
chlorpromazine suffered a 15 percent mortality and the controls a 50
percent mortality. Both drugs also afforded protection against decreased
egg production and shell quality following heat stress.
Investiggtion of Avian Hemodynamics and Dissecting Aneurysm:

Few experiments have been conducted concerning avian hemo-
dynamics. Early work by Stubel (1910) laid the foundation for future
blood pressure research in poultry. Data of Sturkie gtflgl. (1955) reveal
a sex difference in the blood pressures of adult Leghorn chickens to be
greater than that reported in any mammals. The systolic blood pressure
of the male was 15-25 percent higher than that of the female depending
upon age; however, after one year, female blood pressure increased 24
percent as compared with that of males which only increased 14 percent.
These workers also demonstrated that no correlation exists between blood
pressure and body weight. It is noted that the male has a higher blood
pressure and also a higher body weight than the female; however, this is
a casual relationship. Ringer gt'gl. (1957) demonstrated that androgen
is not essential for the rapid rise of blood pressure of the male chicken
and that something other than ovarian activity prevents this rise in the

female. Ringer gt gl. (1955) found age and sex had no influence on the

12.

heart rate and blood pressure of ducks (White Pekin) and pigeons
(White King).

Weiss and Sheahan (1958) and Ringer and Reed (1959) are the
only researchers, thus far, to publish work on the hemodynamic changes
associated with aging in turkeys. The systolic blood pressure of the
adult Jersey Buff turkey is 12-15 percent higher than that of the poult
and was suggested to resemble the hemodynamic pattern of the chicken
(Weiss and Sheahan, 1958). These pressures were higher than those
previously reported for the chicken (Sturkie gtmgl., 1955) or the duck
and pigeon (Ringer's: gl., 1955). Ringer and Rood (1959) working with
Broad Breasted Bronze turkeys demonstrated a significant sexual difference
in systolic, diastolic, and pulse pressures following sexual maturation.
This differs considerably from the work of Weiss and Sheahan (1958). The
male Broad Breasted Bronze turkey exhibited the greatest increase in blood
pressure between 8-20 weeks of age, the age during which aortic rupture
occurs most frequently. No sexual difference was demonstrated in heart
rate and it declined during aging, tending to level off during sexual
maturation. Heart rate follows the same pattern during aging as that of
the duck and pigeon (Ringer 23 31., 1955); however, it is dissimilar to
the heart rate changes reported for the chicken (Sturkie 33 3;” 1955).
iale Broad Breasted Bronze turkeys exhibit a significantly higher blood
pressure than the female and also exhibit a higher incidence of aortic
rupture (McSherry gtflgl., 1954; and Carnaghan 1955). Since Jersey Buff
turkeys do not exhibit aortic rupture, the more recent research of Ringer
and Rood (1959) in Broad Breasted Bronze turkeys is of greater significance
for the study of this problem.

Studies in humans indicate that dissecting aneurysms occur

predominantly in males past middle age in the area of the ascending

150

aortic arch, just above the aortic valves and are due principally to
medial degeneration. According to McSherry.gt‘gl. (1954) dissecting
aneurysms are rare in animals other than birds. In turkeys they are
generally found before maturity. The association between blood pressure
and aortic rupture in turkeys has already been suggested (Gibson and
deGruchy, 1955; Weiss and Sheahan, 1958; and Ringer and Rood, 1959).
Several theories have been proposed as to the possible causes
of dissecting aneurysms (Fig. 5). Carnaghan (1955), a British worker,
and Gottlieb and Lalich (1954), American workers, have suggested that
this condition cocurs together with spontaneous atherosclerotic plaques
or hardening of the arteries of the abdominal region. Arterial aging
and/or injury as a necessary precondition for the development of arterio—
sclerosis was disproven by Rodbard gtugl. (1951) in his studies with
cholesterol, atherogenesis, and aging. He also concluded that the age
of the animal plays a very important role in the regulation of the
atherogenesis. Pollak (1947) believes atherosclerosis results from an
irritation in the subendothelial layer of the arterial intima by
cholesterol deposits. The cause of dissecting aneurysms then, may be
indirectly interrelated with age, cholesterol level, and atherosclerosis.
There is a gross similarity between ruptured aortas of experi-
mental rats fed Lathyrus odoratus seeds and aortas of commercially
raised turkeys which died of aortic rupture. This has stimulated an
attempt by several workers to correlate the condition exhibited in rats
following the feeding of beta-aminopropionitrile (BAPN), the toxic
principle found in sweet pea seeds, with the field cases of aortic rupture
in turkeys. The characteristic symptoms in rats following feeding of this

substance are aortic rupture, internal hemorrhages, and bone deformation,

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(Ponseti and Baird, 1952; Bachhuber and Lalich, 1955; and McKay gt gl.,
1954). Similar responses in turkey poults fed BARN were noted by Barnett
32 2;. (1957), Lalich 93.. 5;. (1957), and h’aibel and Pomeroy (1958).
However, to date no one has been able to isolate this toxic substance
from any normal turkey ration, thus the correlation between the two
conditions may be coincidental.

The objective of the research reported in this thesis is to
study the problem of aortic rupture in turkeys from.a physiological
rather than a nutritional standpoint. For this study economical levels
of an oral tranquilizer, Reserpine, were incorporated into the ration

in an attempt to minimize stress and hypertension.

16.

. OBJECTIVES
This study was designed to supplement others of recent years
by furnishing a comprehensive study and evaluation of the hemodynamic
picture of the maturing Broad Breasted Bronze turkey under normal and
stress conditions after oral tranquilizer administration. It was also
designed to demonstrate the non-toxic level of Reserpine required to
reduce blood pressure. t was hoped this would afford protection
against aortic rupture.
The objectives of this research project were to:
(a) Determine whether Reserpine was a physiologically active
tranquilizer in turkeys.
(b) Establish the dosage level necessary for economical yet
effective response.
(c) Measure hemodynamic and other physiological factors in the
turkey after the administration of an oral tranquilizer.
(d) Establish the rapidity with which a dietary tranquilizer
produces a physiological response.
(e) Determine the effect of long-range feeding of a tranquilizer

to turkeys.

17.

GEIERAL EKPERIXEETAL PROCEDURE

The same general procedures were employed throughout the
entire research project. All of the experimental animals were turkeys
of the Broad Breasted Bronze variety and were hatched by the Michigan
State University Poultry Science Department. Pure Reserpine was used
in each experiment and was premixed in a closed mixer before incorporation
into the feed. Rew feed was mixed every four weeks for the long term
experiments. Starter and grower batteries were employed for all experiments
inwhich turkeys under ten weeks of age were used. All birds, treatments,
and locations were randomized as completely as possible by the selection
of numbers from.a box.

Blood Pressure Determination:

 

An identical method for determining arterial blood pressures
was used throughout the experiments, namely, the direct technique.
Direct measurements were taken in unanesthetized animals held in a
supine position on a wooden holder. The common carotid artery was
exposed surgically by a longitudinal incision in the neck. The artery
was clamped and the cranial end tied permanently. A small nick was made
in the artery between the tie and the clamp; a polyethylene tube (i. d.
0.045 in. x o.d. 0.062 in. and 50 cm. long) was then inserted and tied
in place. The cannula system was connected to a Stratham pressure transducer,
(Model P-25-156-255) which recorded through a Brush amplifier and direct
writing oscillograph. Both the cannula and pressure transducer were
filled with ten percent sodium citrate solution. The pressure equipment
was calibrated through the same transducer by means of a three—way valve

which permitted connection of a mercury manometer as well as filling of

18.

the cannula.
Statistical_Analysis:

All data were statistically analyzed using the Duncan Multiple
Range Test (Duncan, 1955) and the Analysis of Variance and "t" method

(Snedecor, 1946).

19.

EXPERILLEEIT 1

Very few experiments have been reported concerning the usage
of Reserpine in turkeys. It was necessary,.therefore, to conduct an
exploratory pilot experiment to establish dosage and observe the effect
of various levels of Reserpine on hemodynamics and weight gains in the
Broad Breasted Bronze variety of turkeys.

Twenty-four turkeys were randomly assorted into four treatments
in replicate comprising a total of eight equal lots. The treatments
were control, 0.1 ppm., 1.0 ppm., and 4.0 ppm. Reserpine, and were also
randomly distributed into a growing battery divided along the center.

Reserpine was incorporated into a turkey starter mash and
treatment began when the turkeys reached five weeks of age (March). Feed
and water were administered g3 libitum. Discrimination between the sexes
was omitted as the hemodynamic picture does not exhibit sexual divergence
at such an early age (Ringer and Reed, 1959). Blood pressures and weight
gains were recorded at seven and nine weeks of age (two and four weeks
respectively after initiation of treatment) and the experiment terminated
at the latter date. Excess feed wastage prevented a concise determination
of feed efficiency.
Results and Discussion:

The statistical analysis of hemodynamic changes and weight
gains following two and four weeks feeding of Reserpine are shown in
Tables I and II respectively. The data presented in Table I revealed
a highly significant (P <10.01) difference among lots. At seven weeks
of age all levels of Reserpine significantly lowered systolic and diastolic
blood pressures and heart rate; however, pulse pressure remained unchanged.

A significant (P <10.05) difference in weight gains indicates that the

20.

higher levels (1.0 ppm. and 4.0 ppm.) seemed to become toxic as evidenced
by reduction in weight gains while the lower level (0.1 ppm.) seemed to
promote growth as evidenced by a.9 percent increase in mean body weight
above the control lot.

Data presented in Table II, at nine weeks of age, reveal a

hig.ly

U)

ignificant reduction in systolic and diastolic blood pressures
and a significant reduction in heart rate in all treated groups from the
normal pattern of the control lot. The pulse pressure remains unchanged.
There is a highly significant difference in mean weight gains. This
difference is apparently due to the large reduction in weight gain of
those birds receiving high level Reserpine (4.0 ppm.) as compared to the
gain of the control lot. The 0.1 ppm. level again showed a tendency

toward growth stimulation; however, this time it was not significant.

21.

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EXPERIXEKT 2

The relative success of the initial experiment prompted the
author to exploit a second pilot experiment in order to further refine
his dosage level. A level of 0.5 ppm. Reserpine was selected because
it was approximately half-way between the 0.1 ppm. level which reduced
blood pressure and promoted growth and 1.0 ppm. Reserpine, which greatly
reduced blood pressure but also reduced weight gains. The level selected
was expected to give good hypotensive effects without reducing weight
gains.

The experimental design was similar to Experiment 1 in that
twenty-six turkeys were randomly assorted into two treatments in replicate
comprising a total of four equal lots. The treatments were control
and 0.5 ppm. Reserpine and were also randomly divided into levels of the
same growing battery.

Reserpine was incorporated into a turkey starter mash and
treatment began when the turkeys reached four weeks of age (Kay). Feed
and water were administered gdllibitum. Sexual differentiation was again
omitted and blood pressures and weight gains recorded at six and eight
weeks of age (two and four weeks respectively after initiation of treatment)
and the experiment terminated at the latter date. Feed efficiency was not
recorded.

Results and Discusgiggz

The statistical analysis of hemodynamic changes and weight
gains following two and four weeks of feeding Reserpine are presented
in Tables III and Iv, respectively. The data shown in Table III again
revealed a highly significant (P < 0.01) difference in systolic blood

pressure and a significant (P-< 0.05) difference in diastolic blood pressure

24.

and heart rate. Pulse pressure remained non-significantly different and
there was no adverse effect upon weight gain. These findings promised
rewarding results with future usage of this hypotensive agent.

Data presented in Table V over a longer period of Reserpine
administration (4 weeks) still demonstrated a significant reduction in
systolic and diastolic blood pressures; however, pulse pressure and
heart rate remained unchanged. Weight gains tended to be higher in the
0.5 ppm. Reserpine level; however, they were not significantly different

from the control lot.

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27.

EXPERIMENT 5

The first two experiments showed that Reserpine will produce a
hypotensive condition when fed at the level of 0.5 ppm. or less of the
ration without adversely effecting weight gains. A third experiment was
designed to pin-point the exact level at which Reserpine will reduce blood
pressure with no adverse effect on growth.

For this experiment, fifty turkeys were randomly assorted into
five treatments in replicate comprising a total of ten equal lots. The
treatments were control, 0.1 ppm., 0.2 ppm., 0.5 ppm., and 0.4 ppm.
Reserpine and were also randomly distributed into growing batteries.

Reserpine was incorporated into a turkey growing mash and treat-
ment begun when the turkeys reached six weeks of age (July). The birds
were maintained in a manner described for the previous experiments.

Blood pressures were recorded at eight and ten weeks of age (two and four
weeks respectively, after initiation of treatment). Weight gains were
determined at ten weeks of age, at which time the experiment was terminated.
Results and Discussion:

The hemodynamic changes recorded at eight and ten weeks gave

surprising results as will be noted in Tables V and VI respectively.

Jone of the blood pressure recordings was significantly different nor

did any of the levels of Reserpine even tend to reduce the blood pressure
of the treated groups lower than that of the control group. The conditions
of this experiment must be explained. The blood pressure recordings were
taken during a hot summer month, July, a month when heat stress conditions
were very severe, especially in the building in which the turkeys were
raised. The control blood pressures were much lower than the control

blood pressures had been in previous experiments. The heat, which was

the only variable other than tranquilizer level, must have influenced the

28.

normal blood pressure pattern. Weiss 23 5;. (1957) observed a seasonal
difference in the blood pressure of the chicken. Both male and female
blood pressures declined during summer months. The above data reveal

a seasonal difference in the hemodynamics of turkeys.

The Analysis of Variance of weight gains exhibited during the
four week period of treatment revealed a significant (P‘< 0.05) difference
in weight gain, even during conditions of severe heat stress. Turkeys
receiving 0.1 ppm. and 0.5 ppm. Reserpine demonstrated the greatest
significant weight gain over the controls. Birds on the 0.1 ppm.
exhibited an 18 percent increase in weight gain when compared to the
control lot. A weight gain of this magnitude would certainly be
advantageous to poultrymen, especially during the hot summer months when

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51.

EXPERIMEKT 4

The results obtained in the previous experiments prompted a
more comprehensive experiment to substantiate the findings concerning
a possible growth stimulation by Reserpine. This necessitated a long
range experiment designed especially to evaluate weight gains on a
weekly basis as well as total gains for the duration of treatment.

For this experiment, 160 poults were distributed into twenty
equal lots and assorted so each group would contain a comparable weight
distribution. Five treatments in quadruplicate were randomly assorted
among the levels of five starting batteries. The treatments were control,
0.1 ppm., 0.2 ppm., 0.5 ppm., and 0.4 ppm. Reserpine.

Reserpine was incorporated into a turkey starter mash and
treatment initiated when the turkeys reached one week of age (June).

The turkeys were moved to growing batteries at four weeks of age after
which they received turkey growing mash. The birds were maintained in a
manner similar to the previous experiments and weights were recorded at
weekly intervals and the gain evaluated. The final weight was recorded

at nine weeks of age. Careful control to eliminate feed wastage was
practiced. Feed efficiency for the entire eight week period was calculated.

At nine weeks of age (eight weeks after initiation of treatment)
blood pressures were recorded from.16 randomly assorted birds from each
lot in an attempt to evaluate the hemodynamic changes following a long
range treatment period.

Results and Discussion:

 

The statistical analysis of weekly and total weight gains and
the comparison of the means by the Duncan Method (1955) are presented

in Table VII. A weekly analysis of the results reveals a significant

52.

difference in weight gains during all weeks except the first, second and
sixth weeks of treatment; however, an analysis of the long term weight
gains reveals no significant difference between any of the means. There
were no consistant differences among the lots during the course of the
experiment. Feed efficiencies for the entire experiment were control -
5.02 lbs., 0.1 ppm. - 2.87 lbs., 0.2 ppm. - 2.85 lbs., 0.5 ppm. - 2.96 1133.,
and 0.4 ppm. - 5.01 lbs. of feed per pound of gain. These results
demonstrate a greater tendency toward increased feed efficiency at the

0.1 ppm. and 0.2 ppm. levels of Reserpine.

Table VIII presents the statistical analysis of hemodynamic
changes following long term (eight weeks) feeding of Reserpine. The
data reveal a highly significant (P‘<.0.01) difference existing between
systolic and diastolic blood pressures and heart rate of all levels of
treatment when compared to the control lot. A significantdifference
(P <10.05) was also found to exist between pulse pressures.

These results compare favorably with those of the first three
experiments. The question immediately arises as to how long will be
required to produce these hypotensive effects after initiation of the

”treatment.

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EXPERIMEET 5

Since oral administration of Reserpine to young turkeys has been
proven to exert definite hypotensive effects, the question remains as to
the rapidity with which these effects are produced after administration
of the drug.

Sixty-four turkeys were randomly assorted into two treatments,
each with eight replicates comprising a total of sixteen equal lots.

The treatments were control and 0.5 ppm. Reserpine. A high level was
chosen to insure that a definite effect would be produced.

Reserpine was incorporated into a turkey grower mash and fed
to turkeys eleven weeks of age. Blood pressures were recorded at two day
intervals following the initiation of Reserpine treatment until a definite
hypotensive effect was observed.

Results and Discussion:

The hemodynamic changes following two days feeding of Reserpine
are presented in Table IX. After two days of administration there were
no significant hemodynamic changes.

The hemodynamic changes following four days feeding of Reserpine
are presented in Table X. Systolic blood pressure was noted to decrease
significantly in the 0.5 ppm. lot while the other hemodynamic responses
remained significantly unchanged. Since systolic blood pressure exhibited
a significant alteration, it was concluded that Reserpine acts within

four days in turkeys following oral administration.

 

 

 

 

 

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EXPERIN‘WT 6

The previous experiments have demonstrated dosage level and
time required to obtain physiological effects with an oral tranquilizer.
Aortic rupture, however, has only been reported in birds approaching
sexual maturity (10-20 wks.), hence, a long term experiment was conducted
to study the hemodynamic response of older birds to oral Reserpine
administration.

For this investigation 120 turkeys were raised in batteries
until eight weeks of age at which time they were divided into four
equal lots and placed in brooder houses. Reserpine was incorporated
into a turkey grower mash and treatment begun when the turkeys reached
nine weeks of age (July). The turkey grower was in the form of crumbles.
The treatments were control, 0.1 ppm., 0.5 ppm., and 1.0 ppm. Reserpine.
Ten days later the lots were moved onto range and each lot assigned
a shelter which was enclosed by wire to separate the treatments. Feed
and water were administered ad lifigjgg, Sex was determined later in
the experiment when sexual differences were easily recognized.

Initial blood pressure recordings on ten birds per lot were
determined at four week intervals, namely eleven, fifteen, and nineteen
weeks of age. Subsequent blood pressures were recorded on these same
birds two weeks following the initial blood pressure recording or at
thirteen, seventeen, and twenty-one weeks of age, respectively. The
duration of tranquilizer administration was twelve weeks.

At the last blood pressure determination after normal blood
pressures were recorded, the turkeys (age 21 wks.) were subjected to a
known stress (0.5 cc. of 1/25,000 dilution of epinephrine injected

intravenously) and the percent change in hemodynamics observed.

\N
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Results and Discussion:

 

Data for both sexes were pooled at each recording until nineteen
weeks of age after which recordings of male and female blood pressures.
were analyzed separately because turkeys do not exhibit a sexual divergence
in blood pressure until after seventeen weeks of age (Ringer and Reed, 1959).
The statistical analysis of hemodynamic changes at each blood pressure
recording are presented in Tables XI through XVI. .

In general, systolic blood pressure of the treated lots was
lower than that of the control lot with the greatest reduction in pressure
occurring in the 1.0 ppm. Reserpine level, followed by the 0.5 ppm. level
while the 0.1 ppm. level of Reserpine differed slightly from the control.
The tranquilizer was mixed into crumbles increasing the possibility of
partial less of the 0.1 ppm. level of Reserpine during mixing and when
placed on range. The systolic blood pressure of the control lot increased
at a phenomenal rate with age confirming the work of Ringer and Rood (1959)
while the treated lots tended to level off.

Diastolic blood pressure tended to increase with aging in all
groups but in the control lot it more closely paralleled systolic blood
pressure than it did in the treated lots. This is reflected by a greater
increase in pulse pressure in the control lot than was exhibited by the
treated lots. Initial pulse pressures were non-significantly different;
however, in the later recordings there was a definite trend for significant
differences between the pulse pressures.

Initial recordings demonstrated a reduction in heart rate by
the higher levels of Reserpine. The final weeks of recording.after birds

were separated according to sex, revealed a significant reduction in the

#0.

heart rate of the male with a tendency toward a lower heart rate of the
female.

To test whether Reserpine treated birds responded differently
to a stress, epinephrine, which is released by the adrenal medulla
during stress, was intravenously injected. An analysis of the percent
change in hemodynamics following epinephrine injection is presented in
Table XVII. Systolic and pulse pressures in lot 4 were found to increase
significantly from.those of the control. Diastolic blood pressure and
heart rate demonstrated no significant changes. As yet, these results

cannot be explained.

41.

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GENERAL DISCUSSION

Dissecting aneurysm (aortic rupture), as the name implies,
is a seepage of blood through the wall of the aorta leading eventually '
to rupture and death of the animal. The exact cause of how the seepage
begins is unknown; however, it is believed to be initiated by an
anatomical change in the vessel wall which soon develops into a weakened
area. The progressively weakening area subjected to alternating pressures
found in the arterial system soon cannot withstand the high arterial
pressure and balloons out leading to final rupture. The significance
of this condition in the turkey industry has been mentioned by
Waibel (1958).

Many theories have been advanced as to the possible origin of
the change in the vessel wall. Studies in humans indicate that medial
degeneration of the aorta is responsible for this condition. Athero-
sclerosis has a tendency to cause vascular weakness and rupture (Best
and Taylor, 1956). The association between atherosclerosis and aortic
rupture has already been suggested by Carnaghan (1955). Pollak (1947)
believes atherosclerosis results from an irritation of the subendothelial
layer of the arterial intima by cholesterol deposits. Best and Taylor
(1956) believe atherosclerosis is due to a disorder of lipid metabolism
especially cholesterol. Also occurring in the aging bird is calcium
deposition in the vascular media. This is apparently a normal process
and is not dependent upon atherosclerotic changes in the intima (Cowdry,
1935). Further investigation by Rodbard 93 5;. (1951) disproved
arterial aging and/or injury as a necessary precondition for the

development of arteriosclerosis.

1+9.

The male chicken is prone to atherosclerosis at an early age
(20 wks.), with calcium deposition occurring largely in the interrenal
area of the dorsal aorta while only minor calcium deposition occurs in
the interrenal area of the female (Katz and Stamler, 1955). Although
the condition of aortic rupture has not been reported in chickens and
a similar condition of calcium deposition has not been found in turkeys,
the problem of spontaneous atherosclerosis is known to exist in turkeys
(Carnaghan, 1955). As an artery becomes thicker and less elastic, it
may crack under increasing pressure conditions similar to those exhibited
by the male turkey under normal and stress conditions. In chickens
approaching maturity there is a significant increase in blood pressure,
with that of the male being predominantly greater than that of the female
(Sturkie gt gl., 1955). A similar increase in blood pressure has been
reported in Jersey Buff turkeys with the tom demonstrating a significant
increase over the hen (Weiss and Sheahan, 1958). These workers found
mature tom turkeys (22 wks.) to average about 226 mm. mercury with
individual turkeys exhibiting phenomenally high blood pressures of about
280 mm. mercury. This is far above the blood pressure of mammals; for
example, the human is considered hypertensive if his pressure exceeds
140-150 mm. mercury, regardless of age.

To the author's knowledge, the Jersey Buff turkey has never
exhibited the condition of aortic rupture. The male Broad Breasted
Bronze variety of turkey at maturity averages a normal blood pressure
of 296 mm. mercury, Ringer and Rood (1959), or twice that of the human.
Individual turkeys of this variety have reached 400 mm. mercury pressure.
Aortic rupture in turkeys has been found to occur mainly in males and

only in the interrenal area of the aorta. Since this area is subject

50.

to atherosclerotic and calcareous plaques plus phenomenally increased
hemodynamics, it is feasible that blood pressure may be the initiating
factor leading to a build-up of fats and minerals in this area thus
promoting intimal or medial degeneration resulting in the final aortic
rupture. Human atherosclerosis and arteriosclerosis are the result of
long-standing hypertension and these generalized vascular changes are
the result, rather than the cause, of hypertension (Grollman, 1957). It
is also possible that calcium and fatty deposition may occur to such an
extent in the male as to significantly narrow the aortic lumen and in
this manner increase blood pressure. It is apparent that the use of a
tranquilizer would not only reduce stress but also lower blood pressure
and thus afford protection against the condition of aortic rupture.

A common tranquilizer, Reserpine, was selected for this
investigation because of its hypotensive properties. In the turkey, mean
arterial blood pressure was reduced by all levels of Reserpine used, the
greater decrease resulting from the higher level of Reserpine employed.
High dosage levels such as 0.4 ppm. Reserpine and higher, approached toxic
conditions as evidenced by reduced weight gains and feed efficiency.

The site of action of Reserpine in mammals appears to be in the
central nervous system due to its definite calming or sedative effect.
The production of hypothermia in mammals, Conner and Haas (1955), and
in birds, Hoffman (1958), suggest the hypothalmus to be affected. Plummer
23 El: (1955) explains the action of Reserpine on the basis of an
alteration of sympathetic-parasympathetic balance by partial suppression
of the sympathetic predominance at the hypothalmic level.

If the distensibility of the arterial system is reduced, thus

51.

increasing central resistance, such as might be the case with turkeys
exhibiting spontaneous aortic atherosclerosis, the normal hemodynamic
pattern is altered. Systolic blood pressure increases tremendously.
Pulse pressure must also increase significantly to assure a normal
blood flow through the tissues; this is reflected in a lower diastolic
blood pressure. A somewhat similar hemodynamic pattern was exhibited
by the untreated turkeys from ten to twenty-one weeks of age. Systolic
blood pressure increased 41 percent and diastolic blood pressure
increased only 29 percent which was reflected by a 68 percent increase
in pulse pressure. Since the heart rate alone plays a minor role in
controlling blood pressure in the chicken, Sturkie (1954), greater
emphasis was placed on the relationship between peripheral resistance
and arterial hemodynamics than on heart rate. A slight bradycardia was
exhibited by turkeys under a long range, high level, treatment of
Reserpine, probably by sympathetic suppression at the hypothalmic level.

The hypotensive results following Reserpine administration to
turkeys appear to be due to a reduction in peripheral resistance based
on the hemodynamic analysis by Wiggers (1952). Systolic and diastolic
blood pressures increased about the same, namely 55 and 51 percent
respectively, while pulse pressure increased 49 percent. The probability
of a combination of distensibility and heart rate changes may exist.
The time to produce effective responses plus the variation in pulse
pressure suggest a mechanism other than direct action.may be involved
in this hemodynamic response to Reserpine administration.

Rauwolfia alkaloids, such as Reserpine, that exert a tranquilizing

effect in animals have been demonstrated to release serotonin

52.

(5-hydroxytryptamine), a powerful vasoconstrictor, from the intestines,
platelets, and brain (Brodie gt gl., 1956; Shore gt 21., 1957; and
Carlsson 33 31., 1957). Serotonin liberation increases at a linear
rate with increasing levels of Reserpine (Carlsson gt.gl., 1957). The
vasoconstrictive influence on peripheral vessels produced by serotonin
may be responsible for persistent hypertension (Page, 1958). Reserpine
acts in the mammal in some unknown way by releasing bound serotonin
(Shore _e_t_ al-» 1957). The free, unstable form is readily metabolized by
monoamine oxidase, (Shore 23 $1., 1957); hence, under long term admin-
istration of Reserpine, a low level of serotonin would persist, resulting
in reduced vasoconstriction and indirect reduction in blood pressure.
Green (1957) demonstrated that blood serotonin fell to non-detectable
levels after administration of Reserpine for a three week period. Reserpine
action then, is supposedly due indirectly to an alteration in brain
serotonin which in turn affects peripheral resistance and resulting
hemodynamic changes. This would explain the delayed action of Reserpine
as serotonin stores must first be depleted before a difference in
hemodynamics is observed. The constant hypotensive action of Reserpine
may then be due to the persistent depletion of serotonin levels which may
be necessary for maintaining normal blood pressure.

Another factor suggesting Reserpine-serotonin relationship
in the bird is that a profound hypothermia is produced following either
Reserpine or serotonin administration (Hoffman, 1958). This differs from
the hypothermia action of Reserpine, Earl (1956), and the hypertherima
produced by serotonin in mammals (Horita, 1954).

Particular attention should be directed toward the increased

weight gains and feed efficiencies observed during long range, low
level, oral administration of Reserpine to young turkeys. Significant
weight gains and feed conversion have been observed in ruminants.
Increased weight gains in ruminants have been explained from two aspects,
that of beneficial effects on rumen microflora, thus promoting fermentation
or the reduction of intestinal motility (Anonymous, 1958); and that of
slowing food movement through the intestinal tract thus improving feed
efficiency by promoting digestibility and assimilation. Rood gt‘gl. (1958)
using Reserpine in broilers did not observe significant weight gains or
feed conversion. Wolterink gt‘gl. (1958) also feeding Reserpine to
birds confirmed the research of Rood gtwgl. (1958) and observed no
difference in intestinal absorption. When incorporating a mixture of
Reserpine and dienestrol diacetate into the feed, transit rate from
the crop was reduced plus the radioactive tracer reaching the intestine
was absorbed faster suggesting a slower, more efficient assimilation of
feed.

Some of the weight gains in turkeys were recorded during
the hot summer months when heat stress was at a maximum. The resistance
of Reserpine fed chickens to high environmental temperatures has already
been reported by Vanfiatre gt 2l° (1957) and Burger 23.31. (1957). The
hypothermic action of Reserpine may be beneficial to the bird. Although
reduced activity was not observed in the treated lots, Reserpine
administration produced favorable results under stress conditions. This
may have been brought about by maintaining normal feed consumption, by
reducing body temperature, by decreasing intestinal motility thus promoting
feed efficiency and allowing a greater share of metabolism to be directed

toward weight gains or by a combination of any or all of these mechanisms.

54.

SUMMARY AND CORCLUSIONS

Pure Reserpine when incorporated into the feed of Broad
Breasted Bronze turkeys is a physiologically active tranquilizer at
all levels between 0.1 ppm. and 4.0 ppm. Levels between 0.1 ppm. and
0.5 ppm. Reserpine produced the best physiological response. Levels
above 0.5 ppm. Reserpine were apparently toxic as evidenced by a
reduction in weight gains of birds fed these levels.

No noticeable effects of tranquilization were observed as
all lots exhibited the same amount of activity. Birds receiving feed
containing Reserpine showed a hemodynamic response within four days.
Circulatory effects are a gradual, moderate drop in blood pressure and
heart rate through an unknown mechanism. The most pronounced reduction
in hemodynamics was observed in males approaching sexual maturation
following prolonged administration of the drug. Females under similar
conditions did not exhibit as great a reduction.

Long and short duration administration of Reserpine produce
similar hemodynamic responses; however, the hemodynamic response becomes
more pronounced during longer feeding trials as the blood pressure of
untreated lots increases phenomenally with age, especially in the male,
while the blood pressure of the treated lots increases, but at a greatly
reduced rate.

Growth promotion was observed in the low levels during the
long term feeding of Reserpine. This was particularly true under heat
stress conditions and may prove beneficial to poultrymen during the hot

summer months.

55.

Turkeys subjected to a known stress following twelve weeks
feeding of Reserpine exhibited a significantly increased percent change
in hemodynamics, especially those receiving the higher levels. These
findings, as of yet, cannot be explained.

The future outlook for Reserpine as a low level additive to
turkey feed is that it may promote weight gain through increased feed

conversion, yet reduce blood pressure significantly thus affording

protection against aortic rupture.

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