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Hemodynamic Responses Following Reserpine Feeding to Turkeys1,2
Hemodynamic Responses Following Reserpine Feeding to Turkeys1,2 E. W. SPECKMANN AND R. K. R I N G E R Department of Poultry Science, Michigan Slate University, East Lansing, Mich. (Received for publication November 17, 1960)
1
Journal Article No. 2715 Michigan Agricultural Experiment Station. 2 Part of a dissertation submitted by the senior author in partial fulfillment of the requirements for the M.S. degree.
tranquilizing properties). Reserpine was used in an a t t e m p t to minimize stress and reduce hypertension, thus possibly affording protection against aortic rupture. EXPERIMENTAL PROCEDURE A preliminary experiment was conducted to determine an effective dosage level of reserpine in five-week-old male and female BBB turkeys. Treatments were: 0.1 p.p.m., 1.0 p.p.m., and 4.0 p.p.m. pure reserpine incorporated in an all-mash starter ration, and untreated controls. Feed and water were supplied ad libitum. All birds were raised in batteries. Reserpine was administered for four weeks, after which blood pressures and weight gains were recorded. Blood pressures were taken directly from the carotid artery of unanesthetized birds as described by Weiss and Sturkie (1951), except for one modification. Polyethylene tubing, (i.d. 0.045 in., o.d. 0.062 in., and 30 cm. in length) was used instead of a 22-gauge hypodermic needle. The pressure was calibrated through the same transducer. In the first experiment, reserpine was incorporated into a commercial starter ration and fed to BBB turkeys from 1—9 weeks of age. All turkeys were raised in batteries; 160 straight-run BBB poults were distributed into twenty equal lots with comparable weight distribution. Five treatments, in quadruplicate, were randomly assorted. The treatments were: 0.1 p.p.m., 0.2 p.p.m., 0.3 p.p.m., and 0.4 p.p.m. of reserpine, and untreated con-
1292
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A N ASSOCIATION between increased •£ •*• blood pressure and aortic rupture in Broad Breasted Bronze (BBB) turkeys has been suggested (Gibson and deGruchy 1955; Weiss and Sheahan, 1958; and Ringer and Rood, 1959). The latter authors reported t h a t the blood pressures for BBB turkeys are higher t h a n any known mammalian or avian pressures, and higher than the pressure of the Jersey Buff turkey (Weiss and Sheahan, 1958). Ringer and Rood (1959) also reported that the BBB turkey exhibits a sexual difference in systolic and diastolic blood pressure and in pulse pressure following sexual maturity, the male being higher. This finding differs from the hemodynamic pattern reported b y Weiss and Sheahan (1958) who found only pulse pressure differences in Jersey Buffs. The male BBB turkey also exhibits a great increase in blood pressure between eight to twenty weeks of age, the age during which aortic rupture occurs most frequently (Ringer and Rood, 1959), and a higher incidence of aortic rupture (McSherry el al., 1954; Carnaghan, 1955). Aortic rupture has not been reported in Jersey Buff turkeys. The purpose of the experiments reported herein was to study the hemodynamic p a t t e r n of the turkey following the oral administration of reserpine (a drug having hypotensive as well as
1293
RESERPINE AND BLOOD PRESSURE
TABLE 1.—Hemodynamic end points and weight gains in the preliminary study following the feeding of reserpine for four weeks Means Lot 1
Lot 3
Control 0.1 ppm. 1.0 ppm. 4.0 ppm. 4 5 6 6 + 9.20 168.5 191.4 198.8 235.5 ±5.56 131.3 149.2 159.7 185.7 + 5.24 37.3 42.2 39.1 49.8 + 11.75 223.5 211.4 260.7 257.0 + 17.88 592.2 705.6 736.0 698.8
>T
F value
N
8.95** 16.24** 0.81 4.39* 12.40**
. ° £
S
-c ^ f
.
nt
(2-3,3-4) (2-3) Non-significant (1-2,1-4,3-4) (1-2-3)
* Significant at the P<0.05 level. ** Significant at the P<0.01 level. Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. 2 At 9 weeks of age. 3 Weight gains between 7-9 weeks. 1
trols. Blood pressures and heart rates were determined after eight weeks of oral reserpine administration. In the second experiment, 120 straightrun BBB poults were distributed into three equal lots in batteries and fed a conventional starter ration for 9 weeks. At nine weeks of age, the turkeys were moved to a divided range at which time reserpine was incorporated into a commercial grower ration. Reserpine was fed continuously throughout the remainder of the experiment. The treatments were 0.5 p.p.m. and 1.0 p.p.m. of reserpine and untreated controls. Blood pressures were determined at two-week intervals beginning at eleven weeks of age. Blood pressures were determined twice on each bird so that a new sample of birds was used every four weeks. Since the blood pressures were measured directly from the
carotid artery, it was necessary to use different birds at different ages. All data were analyzed using the Duncan multiple range test (Duncan, 1955) and the analysis of variance (Snedecor, 1956). RESULTS
The data from the preliminary study are shown in Table 1. All levels of reserpine significantly lowered systolic and diastolic blood pressure. The pulse pressures were not affected by the treatments. Reserpine at the 4.0 p.p.m. level reduced weight gains. Evidently reserpine at the 4.0 p.p.m. level was too high as evidenced by a reduction in weight gains, thus subsequent treatments will involve lower levels. In other work not reported, reserpine at 0.5 p.p.m. level in the diet reduced blood
TABLE 2.—Total weight gains in Experiment 1 following the feeding of reserpine for eight weeks Means Lot 1
Treatment (ppm reserpine) Number of birds Total weight gains (gms.)1 Feed efficiencies2 Mortality (Percent) 1 2
None 31 1,623 3.02 3
Lot 2 0.1 32 1,684 2.87 0
Total weight gain from 1-9 weeks of age. Pounds feed per pound gain.
Lot 3
Lot 4
Lot 5
0.2 30 1,656 2.83 0
0.3 28 1,720 2.96 3
0.4 30 1,585 3.01 0
Standard error of mean
F value
Non-significan t P>0.05
±43.65
1.39
Non-significant
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Treatment (p.p.m. reserpine) Number of birds2 Systolic BP (mm. Hg) Diastolic BP (mm. Hg) Pulse pressure (mm. Hg) Heart rate (beats/min.) Weight gain (gms.)3
Lot 2
Standard - error of mean Lot 4
1294
E. W. SPECKMANN AND R. K. RINGER
TABLE 3.—Hemodynamic end points in Experiment 1 after the feeding of reserpine for eight weeks
Lot 2
Lot 3
Lot 4
Lot 5
Standard error of mean
F value
Lot 1
Non-significant P>0.05'
None 16 207.6 165.6 42.0 261.0
0.1 16 188.3 150.8 37.6 280.2
0.2 16 184.5 151.6 32.9 266.8
0.3 16 186.6 150.7 35.9 255.8
0.4 16 178.2 139.4 38.8 243.3
±5.47 ±4.51 ±2.03 ±6.77
4.08** 4.51** 2.77* 6.19**
(2-3-4-5) (2-3-4-5) (2-3-4-5,1-2-4-5) (1-3-4,1-2-3)
Means
Treatment (ppm.2 reserpine) Number of birds Systolic blood pressure (mm. Hg) Diastolic blood pressure (mm. Hg) Pulse pressure (mm. Hg) Heart rate (beats/min.)
* Significant at the P<0.05 level. ** Significant at the P<0.01 level. Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. At 9 weeks of age.
1 2
The data of Experiment 2 are presented in Tables 4 and 5. The statistical analyses of hemodynamic end points after two weeks oral administration of reserpine are presented in Table 4, while those for the final determination (after 12 weeks oral administration of reserpine) are presented in Table 5. Each two-week recording of systolic blood pressure is presented in Figure 1. Ringer and Rood (1959) demonstrated that BBB turkeys do not exhibit a sexual divergence in blood pressure until after 17 weeks of age. Thus, data for both sexes in Experiment 2 were pooled through the 17th week of determination, after which the male and female systolic blood pressures are reported separately. SYSTOLIC BLOOD PRESSURE
The mean systolic blood pressure of the male turkeys fed reserpine (Tables 4 and S) was lower than that of the controls. It
TABLE 4.—Hemodynamic end points in Experiment 2 after the feeding of reserpine for two weeks Means
Treatment (ppm. reserpine) Number of birds2 Systolic blood pressure (mm. Hg) Diastolic blood pressure (mm. Hg) Pulse pressure (mm. Hg) Heart rate (beats/min.)
Lot 1
Lot 2
Standard • error of Lot 3 mean
None 10 184.1
0.5 10 176.8
1.0 10 162.6
+ 7.31
11.10**
(1-2)
155.6 28.5 255.2
148.2 28.6 203.9
132.5 30.1 210.0
+ 4.68 + 3.22 + 8.93
13.23** 1.20 7.92**
(1-2) Non-significant (2-3)
F value
Non-significant P>0.05 1
** Significant at the P<0.01 level. Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. 2 At 11 weeks of age. 1
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pressures without adversely affecting weight gains. The blood pressure response was noted two to four days after the oral administration of reserpine. Table 2 presents the data from Experiment 1. An analysis of these data reveals that the weight gains of the replicates were non-significantly (P>0.05) different. The replicates were therefore pooled within each treatment. An analysis of weight gains for the entire eight-week treatment period was non-significant. There were no consistent differences between the lots during the course of the experiment. Analyses of the Experiment 1 hemodynamic end points following the feeding of reserpine for eight weeks are presented in Table 3. The data reveal that a highly significant (P<0.01) decrease existed in systolic blood pressures, diastolic blood pressures, and heart rate at all levels of treatment as compared with the controls.
TABLE 5.—Hemodynamic end points in Experiment 2 after the feeding of reserpine for 12 weeks Means
Sex1 Treatment (ppm. reserpine) No. of birds
3
Lot 1
Lot 2
Lot 3
None
0.5
1.0
4 6
4 6
Standard error of mean
F value
Non-significant P>0.05 2
7 3
Systolic BP (mm. Hg)
M F
310.9 258.0
205. S 251.0 235.3 214.8
+ 17.33 + 17.11
7.23** 1.12
(2-3) Non-significant
Diastolic BP (mm. Hg)
M F
221.9 197.3
169.5 179.3
192.0 163.8
+ 9.51 + 11.02
5.84** 1.70
(1-3, 2-3) Non-significant
Pulse Pressure (mm. Hg)
M F
89.0 60.7
36.0 56.0
59.0 51.0
+ 8.83 ± 8.78
6.80** 0.22
(1-3, 2-3) Non-significant
Heart rate (beats/min.)
M F
227.7 219.3
201.5 199.5 205.0 201.7
+ 6.84 + 11.45
3.63* 3.62*
(2-3) (2-3)
* Significant at the P < 0.05 level. ** Significant at the P<0.01 level. M = male; F = female. 2 Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. 3 At 21 weeks of age. 1
310.9 300- -
280-
260- -
M
^2*
258.0
KEY i CONTROL — o — 0.5 PPM RESERPINE _ _ 1.0 PPM RESERPINE M MALE F FEMALE
24 0
F _ o — ° - ° " 235.3
220. 214.8 kT
205
-5
180- -
160
MALES AND FEMALES SEPARATE I I
FIG. 1. Systolic blood pressure changes with age during the administration of reserpine from 9 weeks to 21 weeks of age.
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M F
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E. W. SPECKMANN AND R. K. R I N G E R
was found t h a t the systolic blood pressure of the control individuals increased at a rapid rate with age. The blood pressures of the treated males were lower t h a n t h a t of the control males after 17 weeks of age. DIASTOLIC AND PULSE PRESSURE
HEART RATE
At 11 weeks of age, the heart rate of the turkeys receiving reserpine (Tables 4 and 5) was significantly lower than t h a t of controls ( P < 0 . 0 1 ) . At 21 weeks of age both the reserpine-fed males and the females showed a significantly lower heart rate t h a n did the male and female controls. All groups of individuals showed a decreased heart rate with aging. DISCUSSION Carlson (1960) studied the effect of reserpine on the growth rate and feed efficiencies of BBB turkeys and found that 1.1 p.p.m. (0.5 mg. per pound feed) of reserpine in the feed could be fed for a four-week period to stop losses from aortic rupture without interferring with growth or feed conversion. In the investigation reported herein, feed efficiencies were improved during the eight-week, low-level, oral administration of reserpine
The central action of reserpine, possibly at the hypothalamic level, (Plummer et al., 1955), may be involved in the hemodynamic response to oral administration of reserpine to turkeys. The release of bound serotonin by reserpine in mammals, (Shore et al., 1957) may also be partially responsible for the decrease in blood pressure following reserpine administration to turkeys as the free serotonin is unstable and readily metabolized; however, this does not fully explain the pronounced hypotension resulting from continued oral reserpine administration. One of the major influences of reserpine is to reduce the systolic blood pressure. In Experiment 2 the control turkeys showed a rather large increase in systolic blood pressure with age while in comparison, the reserpine-fed turkeys showed a small percentage increase in blood pressures with age. This reduction in blood pressure by reserpine could be accomplished
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In the control male birds (Tables 4 and 5), the rise in diastolic blood pressure with age did not parallel the rise in systolic blood pressure which was shown by the increase in pulse pressure (systolic minus diastolic blood pressure) with increasing age. In the treated male birds, however, the rise in diastolic blood pressure more closely paralleled the rise in systolic blood pressure. At 11 weeks of age, the mean of the pulse pressures of treated males and control males were non-significantly different ( P > 0 . 0 5 ) . At 21 weeks of age, however, there was a trend for the pulse pressures to be significantly different (P<0.05).
to young turkeys at the levels of 0.1 p.p.m., 0.2 p.p.m., and 0.3 p.p.m. reserpine. The use of low levels of tranquilizers have improved growth rate and feed efficiency in ruminants (Sherman et al., 1958). Tranquilizers are believed to ameliorate environmental stress without producing measurable sedation (Sherman et al., 1959). Whether tranquilizers slow food movement through the intestinal tract, thereby improving feed efficiency through increased digestibility and assimilation is still questionable. Rood et al. (1958), using reserpine in broilers, did not observe significant weight gains. Wolterink et al. (1958), fed reserpine to broilers and observed no difference in intestinal absorption. The condition of tranquilization or slowed responsiveness was not exhibited by the turkeys used in this investigation, thereby supporting previous work.
R E S E R P I N E AND BLOOD P B E S S U R E
Sturkie (1954) suggested that heart rate alone plays a minor role in controlling the blood pressure in the chicken. After 12 weeks of oral administration of reserpine to BBB turkeys from 9-21 weeks of age a similar p a t t e r n was noted. The turkeys fed 1.0 p.p.m. of reserpine showed an increase in systolic blood pressure of 43.2 percent, an increase in diastolic blood pressure of 34.2 percent, a pulse pressure increase of 83.6 percent, and a heart rate decrease of 4.5 percent with aging. The control individuals showed an increase in systolic blood pressure of 54.5 percent, an increase in diastolic blood presure of 34.7 percent, a pulse pressure increase of 163 percent and a heart rate decrease of 12.4 percent with aging. I t seems quite feasible t h a t heart rate alone also plays a minor role in controlling the blood pressure of the BBB turkey and t h a t the lowered systolic blood pressure of reserpine-fed turkeys may well be a function of an altered cardiac output. The average systolic blood pressure of the male BBB turkey at m a t u r i t y has been reported as 296 mm. mercury (Ringer and Rood, 1959). These researchers also reported t h a t certain individuals of the B B B turkey showed a
systolic blood pressure as high as 400 mm. mercury. Birds frequently die from aortic rupture following a stress such as jumping off a roost or from fright. The marked elevation of systolic blood pressure during stress m a y be sufficient to cause a rupture in the aorta, especially if the aorta was weakened. Turkeys are subject to spontaneous atherosclerosis in the aorta (Carnaghan, 1955), and this could be the weakening source. A bird with high blood pressure (turkeys approaching sexual maturation) would be more inclined to rupture such a weakened aorta during a stress than would a turkey with a lowered systolic blood pressure. A hypotensive tranquilizer, such as reserpine, t h a t not only reduces stress but also lowers the blood pressure, would seem beneficial in affording protection against the condition of aortic rupture. SUMMARY Pure reserpine when incorporated into the feed of BBB turkeys increases weight gains and reduces blood pressure between the levels of 0.1 p.p.m. and 0.3 p.p.m. of the ration. Levels above 0.3 p.p.m. reserpine reduced blood pressure b u t were apparently approaching toxicity as evidenced by a reduction in weight gains of the birds fed these levels. No noticeable effects of tranquilization were observed. Circulatory effects are a gradual, moderate drop in blood pressure and heart rate through an unknown mechanism. The most pronounced reduction in hemodynamic end points 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
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by altering the cardiac output thus increasing the efficiency of the heart. The heart of a reserpine-fed bird may work more efficiently under stress conditions therefore maintaining a lower systolic blood pressure than control birds and in this manner alleviate the possibility of aortic rupture. If the cardiac output is increased, heart rate must be reduced if a lower blood pressure than the control birds is to be obtained; however, in the turkeys fed 1.0 p.p.m. reserpine for 12 weeks, heart rate decreased 4.5 percent with aging while in the control turkeys heart rate decreased 12.4 percent with aging.
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E. W. SPECKMANN AND R. K.
REFERENCES Carlson, C. W., 1960. Further studies with reserpine for growing turkeys and laying hens. Second conference on the use of reserpine in poultry production. CIBA Pharmaceutical Products, Inc., Summit, N. J., 25-31. Carnaghan, R. B. A., 1955. Atheroma of the aorta associated with dissecting aneurysms in turkeys. Vet. Record, 67: 568-569. Duncan, D. B., 1955. Multipe range and multiple F tests. Biometrics, 11: 1-42. Gibson, E. C , and P. R. deGruchy, 1955. Aortic rutpure in turkeys subsequent to dissecting aneurysms. Vet. Record, 67: 650-654. McSherry, B. J., A. E. Ferguson and J. B. Ballantyne, 1954. A dissecting aneurysm in internal hemorrhage in turkeys. Amer. Vet. Med. Assoc. J. 124-125:279-283. Plummer, A. J., A. E. Earl, J. A. Schneider, J. Trapold and W. Barrett, 1955. Pharmacology of Rauwolfia alkaloids including reserpine. New York Acad. Sci. Ann. 59: 8-21.
Ringer, R. K., and K. G. Rood, 1959. Hemodynamic changes associated with aging in the Broad Breasted Bronze turkey. Poultry Sci. 38: 295297. Rood, K. G., R. K. Ringer, E. W. Speckmann and L. F. Wolterink, 1958. The effect of feeding reserpine to growing birds. Michigan Agr. Exp. Sta. Quart. Bui. 41(1): 157-162. Sherman, W. C , W. H. Hale, W. M. Reynolds and H. G. Luther, 1958. Nutritional studies of hydroxyzine and Rauwolfia in cattle and lambs. Proc. Soc. Expt'l. Biol. Med. 98: 91-94. Sherman, W. C , W. H. Hale, W. M. Reynolds and H. G. Luther, 1959. The effect of tranquilizers, diethylstilbestrol and oxytetracycline alone and in combination on performance of steers. J. Anim. Sci. 18: 198-205. Shore, P. A., A. P. Letacher, E. G. Tomick, A. Carlson, R. Kuntzman and B. B. Brodie, 1957. Role of brain serotonin in reserpine action. New York Acad. Sci. Ann. 66: 609-617. Snedecor, G. W., 1956. Statistical Methods, 5th Ed., Iowa State College Press, Ames, Iowa. 534 pp. Sturkie, P. D., 1954. Avian Physiology, 1st Ed., Comstock Publishing Assoc, Ithaca, N. Y., 423 pp. Weiss, H. S., and P. D. Sturkie, 1951. An indirect method for measuring blood pressure in the fowl. Poultry Sci. 30: 587-592. Weiss, H. S., and M. Sheahan, 1958. The influence of maturity and sex on the blood pressure of the turkey. Amer. Vet. Res. J. 19: 208-211. Wolterink, L. F., E. W. Speckmann, K. G. Rood and R. K. Ringer, 1958. The effects of an oral estrogen-tranquilizer combination on transit through the digestive tract and on the intestinal absorption of radio-active phosphorus in broilers fed a low protein ration. Poultry Sci. 37: 1254.
NEWS AND NOTES (Continued from page 1291) G. W. Friars (B.S.A., McGill; M.S., Ph.D., Purdue) completed his doctorate program, and returned to his research position in the Department of Poultry Science, Ontario Agricultural College, in January. A. L. Ramaswamy (Veterinary Diploma, Madras) completed the program for his Master's degree in poultry management and returned to India to continue to serve as Poultry Officer for the State of Andhra Pradesh.
C. A. Blackwood (B.S.A., Vermont) completed his Master's degree program and accepted a position as Assistant Geneticist with the Schultz Animal Breeding Consultants, Livermore, California. P. V. Blair (B. S., Utah State) completed his doctorate in population genetics, and accepted a postdoctorate professorship in enzyme research at the University of Wisconsin. D. C. Englert (B.S., University of Kansas) completed his Master's program in population genetics,
(Continued on page 1352)
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response becomes more pronounced during longer feeding trials as the blood pressure of the untreated lots increases phenomenally with age, especially in the male, while the blood pressure of the treated lots increases, b u t at a greatly reduced rate. Reserpine as a low level feed additive to the turkey ration may be beneficial in t h a t it may increase feed conversion, yet reduce stress and blood pressure enough to afford protection against the condition of aortic rupture.
RINGER
1
Journal Article No. 2715 Michigan Agricultural Experiment Station. 2 Part of a dissertation submitted by the senior author in partial fulfillment of the requirements for the M.S. degree.
tranquilizing properties). Reserpine was used in an a t t e m p t to minimize stress and reduce hypertension, thus possibly affording protection against aortic rupture. EXPERIMENTAL PROCEDURE A preliminary experiment was conducted to determine an effective dosage level of reserpine in five-week-old male and female BBB turkeys. Treatments were: 0.1 p.p.m., 1.0 p.p.m., and 4.0 p.p.m. pure reserpine incorporated in an all-mash starter ration, and untreated controls. Feed and water were supplied ad libitum. All birds were raised in batteries. Reserpine was administered for four weeks, after which blood pressures and weight gains were recorded. Blood pressures were taken directly from the carotid artery of unanesthetized birds as described by Weiss and Sturkie (1951), except for one modification. Polyethylene tubing, (i.d. 0.045 in., o.d. 0.062 in., and 30 cm. in length) was used instead of a 22-gauge hypodermic needle. The pressure was calibrated through the same transducer. In the first experiment, reserpine was incorporated into a commercial starter ration and fed to BBB turkeys from 1—9 weeks of age. All turkeys were raised in batteries; 160 straight-run BBB poults were distributed into twenty equal lots with comparable weight distribution. Five treatments, in quadruplicate, were randomly assorted. The treatments were: 0.1 p.p.m., 0.2 p.p.m., 0.3 p.p.m., and 0.4 p.p.m. of reserpine, and untreated con-
1292
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A N ASSOCIATION between increased •£ •*• blood pressure and aortic rupture in Broad Breasted Bronze (BBB) turkeys has been suggested (Gibson and deGruchy 1955; Weiss and Sheahan, 1958; and Ringer and Rood, 1959). The latter authors reported t h a t the blood pressures for BBB turkeys are higher t h a n any known mammalian or avian pressures, and higher than the pressure of the Jersey Buff turkey (Weiss and Sheahan, 1958). Ringer and Rood (1959) also reported that the BBB turkey exhibits a sexual difference in systolic and diastolic blood pressure and in pulse pressure following sexual maturity, the male being higher. This finding differs from the hemodynamic pattern reported b y Weiss and Sheahan (1958) who found only pulse pressure differences in Jersey Buffs. The male BBB turkey also exhibits a great increase in blood pressure between eight to twenty weeks of age, the age during which aortic rupture occurs most frequently (Ringer and Rood, 1959), and a higher incidence of aortic rupture (McSherry el al., 1954; Carnaghan, 1955). Aortic rupture has not been reported in Jersey Buff turkeys. The purpose of the experiments reported herein was to study the hemodynamic p a t t e r n of the turkey following the oral administration of reserpine (a drug having hypotensive as well as
1293
RESERPINE AND BLOOD PRESSURE
TABLE 1.—Hemodynamic end points and weight gains in the preliminary study following the feeding of reserpine for four weeks Means Lot 1
Lot 3
Control 0.1 ppm. 1.0 ppm. 4.0 ppm. 4 5 6 6 + 9.20 168.5 191.4 198.8 235.5 ±5.56 131.3 149.2 159.7 185.7 + 5.24 37.3 42.2 39.1 49.8 + 11.75 223.5 211.4 260.7 257.0 + 17.88 592.2 705.6 736.0 698.8
>T
F value
N
8.95** 16.24** 0.81 4.39* 12.40**
. ° £
S
-c ^ f
.
nt
(2-3,3-4) (2-3) Non-significant (1-2,1-4,3-4) (1-2-3)
* Significant at the P<0.05 level. ** Significant at the P<0.01 level. Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. 2 At 9 weeks of age. 3 Weight gains between 7-9 weeks. 1
trols. Blood pressures and heart rates were determined after eight weeks of oral reserpine administration. In the second experiment, 120 straightrun BBB poults were distributed into three equal lots in batteries and fed a conventional starter ration for 9 weeks. At nine weeks of age, the turkeys were moved to a divided range at which time reserpine was incorporated into a commercial grower ration. Reserpine was fed continuously throughout the remainder of the experiment. The treatments were 0.5 p.p.m. and 1.0 p.p.m. of reserpine and untreated controls. Blood pressures were determined at two-week intervals beginning at eleven weeks of age. Blood pressures were determined twice on each bird so that a new sample of birds was used every four weeks. Since the blood pressures were measured directly from the
carotid artery, it was necessary to use different birds at different ages. All data were analyzed using the Duncan multiple range test (Duncan, 1955) and the analysis of variance (Snedecor, 1956). RESULTS
The data from the preliminary study are shown in Table 1. All levels of reserpine significantly lowered systolic and diastolic blood pressure. The pulse pressures were not affected by the treatments. Reserpine at the 4.0 p.p.m. level reduced weight gains. Evidently reserpine at the 4.0 p.p.m. level was too high as evidenced by a reduction in weight gains, thus subsequent treatments will involve lower levels. In other work not reported, reserpine at 0.5 p.p.m. level in the diet reduced blood
TABLE 2.—Total weight gains in Experiment 1 following the feeding of reserpine for eight weeks Means Lot 1
Treatment (ppm reserpine) Number of birds Total weight gains (gms.)1 Feed efficiencies2 Mortality (Percent) 1 2
None 31 1,623 3.02 3
Lot 2 0.1 32 1,684 2.87 0
Total weight gain from 1-9 weeks of age. Pounds feed per pound gain.
Lot 3
Lot 4
Lot 5
0.2 30 1,656 2.83 0
0.3 28 1,720 2.96 3
0.4 30 1,585 3.01 0
Standard error of mean
F value
Non-significan t P>0.05
±43.65
1.39
Non-significant
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Treatment (p.p.m. reserpine) Number of birds2 Systolic BP (mm. Hg) Diastolic BP (mm. Hg) Pulse pressure (mm. Hg) Heart rate (beats/min.) Weight gain (gms.)3
Lot 2
Standard - error of mean Lot 4
1294
E. W. SPECKMANN AND R. K. RINGER
TABLE 3.—Hemodynamic end points in Experiment 1 after the feeding of reserpine for eight weeks
Lot 2
Lot 3
Lot 4
Lot 5
Standard error of mean
F value
Lot 1
Non-significant P>0.05'
None 16 207.6 165.6 42.0 261.0
0.1 16 188.3 150.8 37.6 280.2
0.2 16 184.5 151.6 32.9 266.8
0.3 16 186.6 150.7 35.9 255.8
0.4 16 178.2 139.4 38.8 243.3
±5.47 ±4.51 ±2.03 ±6.77
4.08** 4.51** 2.77* 6.19**
(2-3-4-5) (2-3-4-5) (2-3-4-5,1-2-4-5) (1-3-4,1-2-3)
Means
Treatment (ppm.2 reserpine) Number of birds Systolic blood pressure (mm. Hg) Diastolic blood pressure (mm. Hg) Pulse pressure (mm. Hg) Heart rate (beats/min.)
* Significant at the P<0.05 level. ** Significant at the P<0.01 level. Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. At 9 weeks of age.
1 2
The data of Experiment 2 are presented in Tables 4 and 5. The statistical analyses of hemodynamic end points after two weeks oral administration of reserpine are presented in Table 4, while those for the final determination (after 12 weeks oral administration of reserpine) are presented in Table 5. Each two-week recording of systolic blood pressure is presented in Figure 1. Ringer and Rood (1959) demonstrated that BBB turkeys do not exhibit a sexual divergence in blood pressure until after 17 weeks of age. Thus, data for both sexes in Experiment 2 were pooled through the 17th week of determination, after which the male and female systolic blood pressures are reported separately. SYSTOLIC BLOOD PRESSURE
The mean systolic blood pressure of the male turkeys fed reserpine (Tables 4 and S) was lower than that of the controls. It
TABLE 4.—Hemodynamic end points in Experiment 2 after the feeding of reserpine for two weeks Means
Treatment (ppm. reserpine) Number of birds2 Systolic blood pressure (mm. Hg) Diastolic blood pressure (mm. Hg) Pulse pressure (mm. Hg) Heart rate (beats/min.)
Lot 1
Lot 2
Standard • error of Lot 3 mean
None 10 184.1
0.5 10 176.8
1.0 10 162.6
+ 7.31
11.10**
(1-2)
155.6 28.5 255.2
148.2 28.6 203.9
132.5 30.1 210.0
+ 4.68 + 3.22 + 8.93
13.23** 1.20 7.92**
(1-2) Non-significant (2-3)
F value
Non-significant P>0.05 1
** Significant at the P<0.01 level. Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. 2 At 11 weeks of age. 1
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pressures without adversely affecting weight gains. The blood pressure response was noted two to four days after the oral administration of reserpine. Table 2 presents the data from Experiment 1. An analysis of these data reveals that the weight gains of the replicates were non-significantly (P>0.05) different. The replicates were therefore pooled within each treatment. An analysis of weight gains for the entire eight-week treatment period was non-significant. There were no consistent differences between the lots during the course of the experiment. Analyses of the Experiment 1 hemodynamic end points following the feeding of reserpine for eight weeks are presented in Table 3. The data reveal that a highly significant (P<0.01) decrease existed in systolic blood pressures, diastolic blood pressures, and heart rate at all levels of treatment as compared with the controls.
TABLE 5.—Hemodynamic end points in Experiment 2 after the feeding of reserpine for 12 weeks Means
Sex1 Treatment (ppm. reserpine) No. of birds
3
Lot 1
Lot 2
Lot 3
None
0.5
1.0
4 6
4 6
Standard error of mean
F value
Non-significant P>0.05 2
7 3
Systolic BP (mm. Hg)
M F
310.9 258.0
205. S 251.0 235.3 214.8
+ 17.33 + 17.11
7.23** 1.12
(2-3) Non-significant
Diastolic BP (mm. Hg)
M F
221.9 197.3
169.5 179.3
192.0 163.8
+ 9.51 + 11.02
5.84** 1.70
(1-3, 2-3) Non-significant
Pulse Pressure (mm. Hg)
M F
89.0 60.7
36.0 56.0
59.0 51.0
+ 8.83 ± 8.78
6.80** 0.22
(1-3, 2-3) Non-significant
Heart rate (beats/min.)
M F
227.7 219.3
201.5 199.5 205.0 201.7
+ 6.84 + 11.45
3.63* 3.62*
(2-3) (2-3)
* Significant at the P < 0.05 level. ** Significant at the P<0.01 level. M = male; F = female. 2 Numbers joined by a dash are non-significantly different (P>0.05) by the Duncan multiple range and multiple F tests. 3 At 21 weeks of age. 1
310.9 300- -
280-
260- -
M
^2*
258.0
KEY i CONTROL — o — 0.5 PPM RESERPINE _ _ 1.0 PPM RESERPINE M MALE F FEMALE
24 0
F _ o — ° - ° " 235.3
220. 214.8 kT
205
-5
180- -
160
MALES AND FEMALES SEPARATE I I
FIG. 1. Systolic blood pressure changes with age during the administration of reserpine from 9 weeks to 21 weeks of age.
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M F
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E. W. SPECKMANN AND R. K. R I N G E R
was found t h a t the systolic blood pressure of the control individuals increased at a rapid rate with age. The blood pressures of the treated males were lower t h a n t h a t of the control males after 17 weeks of age. DIASTOLIC AND PULSE PRESSURE
HEART RATE
At 11 weeks of age, the heart rate of the turkeys receiving reserpine (Tables 4 and 5) was significantly lower than t h a t of controls ( P < 0 . 0 1 ) . At 21 weeks of age both the reserpine-fed males and the females showed a significantly lower heart rate t h a n did the male and female controls. All groups of individuals showed a decreased heart rate with aging. DISCUSSION Carlson (1960) studied the effect of reserpine on the growth rate and feed efficiencies of BBB turkeys and found that 1.1 p.p.m. (0.5 mg. per pound feed) of reserpine in the feed could be fed for a four-week period to stop losses from aortic rupture without interferring with growth or feed conversion. In the investigation reported herein, feed efficiencies were improved during the eight-week, low-level, oral administration of reserpine
The central action of reserpine, possibly at the hypothalamic level, (Plummer et al., 1955), may be involved in the hemodynamic response to oral administration of reserpine to turkeys. The release of bound serotonin by reserpine in mammals, (Shore et al., 1957) may also be partially responsible for the decrease in blood pressure following reserpine administration to turkeys as the free serotonin is unstable and readily metabolized; however, this does not fully explain the pronounced hypotension resulting from continued oral reserpine administration. One of the major influences of reserpine is to reduce the systolic blood pressure. In Experiment 2 the control turkeys showed a rather large increase in systolic blood pressure with age while in comparison, the reserpine-fed turkeys showed a small percentage increase in blood pressures with age. This reduction in blood pressure by reserpine could be accomplished
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In the control male birds (Tables 4 and 5), the rise in diastolic blood pressure with age did not parallel the rise in systolic blood pressure which was shown by the increase in pulse pressure (systolic minus diastolic blood pressure) with increasing age. In the treated male birds, however, the rise in diastolic blood pressure more closely paralleled the rise in systolic blood pressure. At 11 weeks of age, the mean of the pulse pressures of treated males and control males were non-significantly different ( P > 0 . 0 5 ) . At 21 weeks of age, however, there was a trend for the pulse pressures to be significantly different (P<0.05).
to young turkeys at the levels of 0.1 p.p.m., 0.2 p.p.m., and 0.3 p.p.m. reserpine. The use of low levels of tranquilizers have improved growth rate and feed efficiency in ruminants (Sherman et al., 1958). Tranquilizers are believed to ameliorate environmental stress without producing measurable sedation (Sherman et al., 1959). Whether tranquilizers slow food movement through the intestinal tract, thereby improving feed efficiency through increased digestibility and assimilation is still questionable. Rood et al. (1958), using reserpine in broilers, did not observe significant weight gains. Wolterink et al. (1958), fed reserpine to broilers and observed no difference in intestinal absorption. The condition of tranquilization or slowed responsiveness was not exhibited by the turkeys used in this investigation, thereby supporting previous work.
R E S E R P I N E AND BLOOD P B E S S U R E
Sturkie (1954) suggested that heart rate alone plays a minor role in controlling the blood pressure in the chicken. After 12 weeks of oral administration of reserpine to BBB turkeys from 9-21 weeks of age a similar p a t t e r n was noted. The turkeys fed 1.0 p.p.m. of reserpine showed an increase in systolic blood pressure of 43.2 percent, an increase in diastolic blood pressure of 34.2 percent, a pulse pressure increase of 83.6 percent, and a heart rate decrease of 4.5 percent with aging. The control individuals showed an increase in systolic blood pressure of 54.5 percent, an increase in diastolic blood presure of 34.7 percent, a pulse pressure increase of 163 percent and a heart rate decrease of 12.4 percent with aging. I t seems quite feasible t h a t heart rate alone also plays a minor role in controlling the blood pressure of the BBB turkey and t h a t the lowered systolic blood pressure of reserpine-fed turkeys may well be a function of an altered cardiac output. The average systolic blood pressure of the male BBB turkey at m a t u r i t y has been reported as 296 mm. mercury (Ringer and Rood, 1959). These researchers also reported t h a t certain individuals of the B B B turkey showed a
systolic blood pressure as high as 400 mm. mercury. Birds frequently die from aortic rupture following a stress such as jumping off a roost or from fright. The marked elevation of systolic blood pressure during stress m a y be sufficient to cause a rupture in the aorta, especially if the aorta was weakened. Turkeys are subject to spontaneous atherosclerosis in the aorta (Carnaghan, 1955), and this could be the weakening source. A bird with high blood pressure (turkeys approaching sexual maturation) would be more inclined to rupture such a weakened aorta during a stress than would a turkey with a lowered systolic blood pressure. A hypotensive tranquilizer, such as reserpine, t h a t not only reduces stress but also lowers the blood pressure, would seem beneficial in affording protection against the condition of aortic rupture. SUMMARY Pure reserpine when incorporated into the feed of BBB turkeys increases weight gains and reduces blood pressure between the levels of 0.1 p.p.m. and 0.3 p.p.m. of the ration. Levels above 0.3 p.p.m. reserpine reduced blood pressure b u t were apparently approaching toxicity as evidenced by a reduction in weight gains of the birds fed these levels. No noticeable effects of tranquilization were observed. Circulatory effects are a gradual, moderate drop in blood pressure and heart rate through an unknown mechanism. The most pronounced reduction in hemodynamic end points 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
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by altering the cardiac output thus increasing the efficiency of the heart. The heart of a reserpine-fed bird may work more efficiently under stress conditions therefore maintaining a lower systolic blood pressure than control birds and in this manner alleviate the possibility of aortic rupture. If the cardiac output is increased, heart rate must be reduced if a lower blood pressure than the control birds is to be obtained; however, in the turkeys fed 1.0 p.p.m. reserpine for 12 weeks, heart rate decreased 4.5 percent with aging while in the control turkeys heart rate decreased 12.4 percent with aging.
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REFERENCES Carlson, C. W., 1960. Further studies with reserpine for growing turkeys and laying hens. Second conference on the use of reserpine in poultry production. CIBA Pharmaceutical Products, Inc., Summit, N. J., 25-31. Carnaghan, R. B. A., 1955. Atheroma of the aorta associated with dissecting aneurysms in turkeys. Vet. Record, 67: 568-569. Duncan, D. B., 1955. Multipe range and multiple F tests. Biometrics, 11: 1-42. Gibson, E. C , and P. R. deGruchy, 1955. Aortic rutpure in turkeys subsequent to dissecting aneurysms. Vet. Record, 67: 650-654. McSherry, B. J., A. E. Ferguson and J. B. Ballantyne, 1954. A dissecting aneurysm in internal hemorrhage in turkeys. Amer. Vet. Med. Assoc. J. 124-125:279-283. Plummer, A. J., A. E. Earl, J. A. Schneider, J. Trapold and W. Barrett, 1955. Pharmacology of Rauwolfia alkaloids including reserpine. New York Acad. Sci. Ann. 59: 8-21.
Ringer, R. K., and K. G. Rood, 1959. Hemodynamic changes associated with aging in the Broad Breasted Bronze turkey. Poultry Sci. 38: 295297. Rood, K. G., R. K. Ringer, E. W. Speckmann and L. F. Wolterink, 1958. The effect of feeding reserpine to growing birds. Michigan Agr. Exp. Sta. Quart. Bui. 41(1): 157-162. Sherman, W. C , W. H. Hale, W. M. Reynolds and H. G. Luther, 1958. Nutritional studies of hydroxyzine and Rauwolfia in cattle and lambs. Proc. Soc. Expt'l. Biol. Med. 98: 91-94. Sherman, W. C , W. H. Hale, W. M. Reynolds and H. G. Luther, 1959. The effect of tranquilizers, diethylstilbestrol and oxytetracycline alone and in combination on performance of steers. J. Anim. Sci. 18: 198-205. Shore, P. A., A. P. Letacher, E. G. Tomick, A. Carlson, R. Kuntzman and B. B. Brodie, 1957. Role of brain serotonin in reserpine action. New York Acad. Sci. Ann. 66: 609-617. Snedecor, G. W., 1956. Statistical Methods, 5th Ed., Iowa State College Press, Ames, Iowa. 534 pp. Sturkie, P. D., 1954. Avian Physiology, 1st Ed., Comstock Publishing Assoc, Ithaca, N. Y., 423 pp. Weiss, H. S., and P. D. Sturkie, 1951. An indirect method for measuring blood pressure in the fowl. Poultry Sci. 30: 587-592. Weiss, H. S., and M. Sheahan, 1958. The influence of maturity and sex on the blood pressure of the turkey. Amer. Vet. Res. J. 19: 208-211. Wolterink, L. F., E. W. Speckmann, K. G. Rood and R. K. Ringer, 1958. The effects of an oral estrogen-tranquilizer combination on transit through the digestive tract and on the intestinal absorption of radio-active phosphorus in broilers fed a low protein ration. Poultry Sci. 37: 1254.
NEWS AND NOTES (Continued from page 1291) G. W. Friars (B.S.A., McGill; M.S., Ph.D., Purdue) completed his doctorate program, and returned to his research position in the Department of Poultry Science, Ontario Agricultural College, in January. A. L. Ramaswamy (Veterinary Diploma, Madras) completed the program for his Master's degree in poultry management and returned to India to continue to serve as Poultry Officer for the State of Andhra Pradesh.
C. A. Blackwood (B.S.A., Vermont) completed his Master's degree program and accepted a position as Assistant Geneticist with the Schultz Animal Breeding Consultants, Livermore, California. P. V. Blair (B. S., Utah State) completed his doctorate in population genetics, and accepted a postdoctorate professorship in enzyme research at the University of Wisconsin. D. C. Englert (B.S., University of Kansas) completed his Master's program in population genetics,
(Continued on page 1352)
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response becomes more pronounced during longer feeding trials as the blood pressure of the untreated lots increases phenomenally with age, especially in the male, while the blood pressure of the treated lots increases, b u t at a greatly reduced rate. Reserpine as a low level feed additive to the turkey ration may be beneficial in t h a t it may increase feed conversion, yet reduce stress and blood pressure enough to afford protection against the condition of aortic rupture.
RINGER