Effect of exercise stress on carotid, uterine, and iliac blood flow in pregnant and nonpregnant ewes

Effect of exercise stress on carotid, uterine, and iliac blood flow in pregnant and nonpregnant ewes

Effect of exercise stress on carotid, uterine, and iliac blood flow in pregnant and nonpregnant J. ORR, T. UNGERER, J. B.S. D.V.M. WILL, D.V.M...

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Effect of exercise stress on carotid, uterine, and iliac blood flow in pregnant and nonpregnant J.

ORR,

T.

UNGERER,

J.

B.S. D.V.M.

WILL,

D.V.M.,

KLAUS L.

B.

ewes

PH.D.

WERNICKE, CURET,

Madison,

M.D.* M.D.

Wisconsin

Maternal blood pressure, cardiac output, and carotid, iliac, and uterine blood flow were measured in pregnant and nonpregnant ewes before and during exercise on a treadmill. Mean arterial pressure remained unchanged while cardiac output and carotid and iliac blood flow were increased. Uterine flow was not impaired by maternal exercise.

Materials

past several years, we have been interested in the effect of exercise on the distribution of blood to the various organs. Alterations in uterine blood flow in the pregnant ewe with possible deleterious consequences for the fetus have been of particular concern, and this study was performed to elucidate these possible alterations. This is the first report on a long-term study which hopefully will finally clarify the uterine and umbilical vascular responses to exercise. D u R I N G T H E

This study was supported by United States Public Health Service Grant Number HDO-3255-03 and American Heart Association Grant Number 70936. for publication for publication

March 9, 1972. June 1, 1972.

Reprint requests: Luis B. Curet, M.D., Dep. Gyn./Ob.. vniversity of Wisconsin, $;:;;l of Me&me, Madison, Wisconsin *Present Obstetrics, Frankfurt,

methods

Six purebred Dorset ewes were used in these experiments. The animals were fasted for 24 to 48 hours and, on the day of operation, were premeditated with scopolamine (0.4 mg.) intramuscularly. Anesthesia was induced with ketamine (0.5 to 1.0 Gm.) intramuscularly and maintained with halothane administered endotracheally. The ewes were placed on their backs, and, under sterile conditions, the abdomen was opened; Doppler ultrasonic transducers were applied to one uterine artery and one external iliac artery. Before dissecting the areolar tissue around the arteries, it was infiltrated with a solution of phenoxybenzamine (50 mg.) in 50 ml. of 1 per cent lidocaine to prevent arterial spasm. After the transducers were tied around the arteries, the peritoneum was closed over them, and the abdomen was closed. The wire leads were tunneled subcutaneously and exteriorized at the flank where they were held in a leather pouch sutured to the body wall. The groins were then opened, and polyvinyl catheters 0.047 inches inside

From the Department of Gynecology and Obstetrics, School of Medicine, and the Department of Veterinary Science, College of Agricultural and Life Sciences of the University of Wisconsin.

Received Accepted

and

address: Dept. of GynecologyUniversity of Frankfurt, West Germany.

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diameter and 0.067 inches outside diameter were threaded through the saphenous arteries into the descending aorta. These catheters were also tunneled to the flank and kept in the leather pouch. One carotid artery was then exposed, and a Doppler ultrasonic transducer was placed around it. The wire leads were folded over and taped to the neck under a protective bandage. The ewes were then allowed to recover, and the first experiment was carried out one week later. During the interval, the blood flows were measured daily and in all animals, by the end of the week, were reasonably stable. On the day of an experiment, a polyvinyl catheter 0.047 inches inside diameter and 0.067 inches outside diameter was inserted through the jugular vein into the right ventricle. A total of 44 experiments were performed on the ewes. The animals were divided into 2 groups; one consisted of 4 pregnant and the other of 2 nonpregnant ewes. One animal delivered twins after 8 experiments had been carried out. Following delivery, 4 more experiments were done on this ewe, and it was considered in both the pregnant and nonpregnant groups. Experiments were performed on the pregnant animals at various times during their gestations between 93 days and term for a total of 28 experiments. Sixteen experiments were performed on the nonpregnant ewes. Each experiment was divided into 4 periods, and cardiac output, arterial blood pressure, heart rate, and uterine, carotid, and external iliac blood flow were measured in each period. The first period was a control one. Recordings were made with the animal standing on the treadmill. During the second and third periods, the animals were exercised on a treadmill at 3 m.p.h. and 10 per cent elevation. The method consisted of exercising the ewe until exhaustion for one period only in the first experiment. Exhaustion was taken to be when the ewe could no longer be forced to run on the treadmill. In the following experiments, the length of the first exercise period was equal to the total length

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Fig. 1. Changes in cardiac index, heart rate, stroke index, and mean arterial blood pressure during each period of all experiments in all animals.

of the time the ewe was exercised in the previous experiment. The second period was the additional length of time required for exhaustion. Measurements were made immediately upon stopping the treadmill. The fourth period of the experiment was a second rest period one hour after the last exercise period. The mean total exercise time for all experiments was 34 4 2.2 minutes per experiment. Pulsatile and mean arterial blood pressures from the aorta were monitored on a Gilson polygraph (Gilson Medical Electronics, Inc., Middleton, Wisconsin), externally coupled to a Statham P23Db strain gauge (Statham Instruments, Inc., Oxnard, California) . The transducer was calibrated by use of a mercury manometer, and zero reference was at the scapulohumeral joint. Cardiac output was measured by the indicator dilution technique with the use of indocyanine green as the indicator. Dye was injected by means of a calibrated syringe. Sampling from the aorta was done by using a DTL densitometer and recorded on the servo channel of the Gilson polygraph. Constant withdrawal rates were accomplished by a

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Harvard withdrawal infusion pump (Harvard Apparatus Co., Millis, Massachusetts). Calibrations for the cuvette were recorded for each experiment by using a serial dilution of the dye in the blood of the animal to obtain deflections for given amounts of dye. Blood velocity was measured by Doppler ultrasonic flowmeters (Parks Electronic Laboratory, Beaverton, Oregon). The transducers were externally coupled to the flowmeter, and the meter was in turn coupled to a three-channel Cardiopan (North American Phillips Company, New York, New York) which recorded the phasic velocity curves. Blood velocity is directly proportional to blood flow if the circumference of the vessel remains constant. It was assumed that the diameters of the vessels did not change appreciably during the experiment because of the snugness of the probe on the vessel and the size of the artery in which flow was measured. Calibrations for determination of absolute flow were not necessary because alterations were calculated in per cent change from rest values. In order to maintain all other variables besides the actual flow velocity constant, settings on the flow meter, including tuning frequency, input, and output of the transducer, were not changed once an experiment was begun. Flow measurements were monitored serially before exercise, immediately following the exercise periods, and one hour post exercise. Zero flow with a stable base line was obtained by means of an electrical zero, simply disconnecting the lead wire from the transducer to the meter. Mean flows were then calculated by use of a planimeter. Statistical analysis of the data was made by use of an IBM 1620 computer. The program consisted of an analysis of variance with total variance of all observations being partitioned according to appropriate sources of variation. F values were obtained and compared to tabular values for tests of significance. Results The results are summarized in Figs. 1, 2, and 3. Cardiac output and stroke volume are expressed as cardiac index and stroke index

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so as to give physiologic validity to comparisons between animals. Body surface, in square meters, was assumed to equal 9.0 x weight (in kilograms) 2h.l Three of the pregnant ewes delivered normal lambs at term; one aborted 3 days after the last study. This ewe had evidence of respiratory infection, and blood studies were positive for Q fever infection.2 Fig. 1 demonstrates the dramatic increase in cardiac index and heart rate as a result of exercise. The increase in both parameters over 100 per cent above the resting values is highly significant (P < 0.01) . Neither stroke index nor mean arterial blood pressure changed significantly as a result of exercise in either pregnant or nonpregnant ewes. As shown in Fig. 2, both carotid and iliac blood flow increased during exercise. Iliac blood flow increased 66 per cent over the base-line flows (P < 0.05). Carotid blood flow had the most significant rise with exercise with a 136 per cent rise above resting levels. This paralleled the 120 per cent increase in cardiac index. The increase in carotid blood flow was highly significant (P < 0.01) . The slight increase in uterine blood flow (UBF) in both groups of ewes was not statistically significant. However, as stated before, there was one ewe that was exercised while pregnant and also post partum and was included in both groups of ewes. As UBF does not return to nonpregnant levels immediately after delivery, that ewe introduces a significant error into the nonpregnant group. If it is removed from the nonpregnant group, a difference in the effect of exercise on uterine blood flow between the 2 groups then becomes apparent (see Fig. 3). The increase in flow in the nonpregnant ewes was significant at the 0.05 level. Comment The increase in carotid blood flow probably reflects an increase in flow to the vascular plexus found in the turbinate bones of the sheep. This plexus serves as an excellent heat exchanger, and the increased flow to that area will allow the ewe to lose the in-

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creased amount of heat produced by the exercise. Cerebral blood flow might also be altered, and a specific method for estimating such flow will have to be used in future experiments. The increase in iliac blood flow was to be expected since skeletal muscles have the capacity to regulate blood flow to meet the need for more oxygen during exercise. The increase in UBF in the nonpregnant ewes reflects blood flow to the myometrium and endometrium. Because uterine blood flow in the nonpregnant ewe is small (range 5 to 60 ml. per minute),3-5 an increase of only 4 to 40 ml. per minute may represent a 70 per cent increase in flow. In the pregnant ewe, a similar or even somewhat higher increase in flow would not represent a significant change from base line as such flows range between 500 and 800 ml. per minute.6-8 Greis? has suggested that the uterine (placental) vascular bed is maximally dilated during pregnancy, and placental blood flow is, therefore, at a peak. The realtively small increase in UBF during exercise is consistent with this concept as the slight increase in myometrial blood flow in the pregnant ewe would be obscured by the lack of change in the placental flow, which accounts for 80 to 85 per cent of the total UBF.8 Thus, it would seem that the similar effect of exercise on the myoendometrial flow in both groups of ewes is in agreement with observations of Greiss’ on the similarity of myoendometrial vascular responses in both pregnant and nonpregnant ewes. Obviously, quantitative measurements of UBF (myometrial and placental) are needed to provide experimental confirmation of this explanation. The observed increase in cardiac output due to an increase in heart rate with no change in stroke volume is expected in the untrained animal. It has been shown that athletes can increase their stroke volume prior to a maximal increase in heart rate.lO The reserve for an additional increase in cardiac output by increasing heart rate gives the trained athlete an advantage over his untrained counterpart. It is possible that, if we had continued to exercise the ewes, even-

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tually they might have increased the cardiac output by increasing the stroke volume. The lack of change in mean arterial blood pressure with exercise has been observed by other investigators. lo* I1 The increase in cardiac output must have been matched by a decrease in total peripheral resistance, thus allowing mean arterial blood pressure to remain relatively stable. Ladner and associates12 have concluded that uterine blood flow in pregnant and nonpregnant ewes depends on the mean perfusing pressure. Their observations were made on short-term experiments during which the ewes were anesthetized and various drugs were administered. In our experiments, the ewes were awake, and no drugs were given. Under these circumstances, uterine blood flow, at least in the nonpregnant ewes, in-

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creased in spite of a Iack of change in mean arterial blood pressure. Finally, Emmanouilides and colleagues13 have suggested that maternal exercise may cause fetal hypoxia due to impaired UBF. They base their suggestions on a drop in the fetal blood PO, during maternal exercise. A drop in fetal blood PoZ, however, does not necessarily indicate tissue hypoxia, and, certainly, the absence of fetal acidosis in their experiments would indicate absence of fetal hypoxia. As the experiments reported here show that uterine blood flow is not impaired by maternal exercise to exhaustion, we have concluded that exercise at this level in a healthy animal apparently is not hazardous to the fetus.

REFERENCES

1. Spector, W. S.: In Handbook of BioIogical Data, Philadelphia, 1956, W. B. Saunders Company. 2. Curet, L. B., and Paust, J.: Transmission of Q fever from experimental sheep to Iaboratory personnel. In preparation. 3. Greiss, F. Cl., Jr., and Anderson, S. G.: AM. J. OBSTET. GYNECOL. 103: 629, 1969. 4. Huckabee, W. E., Crenshaw, C., &ret, L. B., Mann, L., and Barron, D. H.: Q. J. Exp. Physiol. 55: 16, 1970. 5. Curet, L. B.: Unpublished observations. 6. Greiss, F. C., Jr.: AM. J. OBSTET. GYNECOL. 112: 20, 1972. 7. Meschia, G., Cotter, J. R., Makowski, E. L., and Barron, D. H.: Q. J. Exp. Physiol. 52: 1, l nr-

8.

Makowski, E. L., Meschia, G., Droegemueller, W., and Battaglia. F. C.: AM. T. OBSTET. G;NECOL. lOl:~O~, 1968. ” 9. Greiss, F. C., Jr.: AM. J. OBSTET. GYNECOL. 96: 41, 1966. 10. Rushmer, R. F.: In Cardiovascular Dynamics, ed. 3, Philadelphia, 1970, W. B. Saunders Company. 11. Van Citters, R. L., and Franklin, D. L.: Circ. Res. 24: 33, 1969. 12. Ladner, Cl., Brinkman, C. R., Weston, P., and Assali, N. S.: Am. J. Physiol. 218: 257, 1970. 13. Emmanouilides, G. Cl., Hobel, C. J., Yashiro, K., and Klyman, G.: AM. J. OBSTET. GYNECOL. 112: 230, 1972.