Depression of uterine blood flow during total umbilical cord occlusion in sheep

Transcription

1 Europ. J. Obstet. Gynec. reprod. Biol., 19 (1985) Elsevier 125 EJO Depression of uterine blood flow during total umbilical cord occlusion in sheep T.H.M. Hasaart and J. de Haan Department of Obstetrics and Gynecology, Annadal Hospital, State University Limburg, P.O. Box 616, 6200 MD Maastricht, The Netherlands Accepted for publication 17 August 1984 HASAAKT, T.H.M. and DE HAAN, J. (1985): Depression of uterine blood flow during total umbilical cord occlusion in sheep. Europ. J. Obstet. Gynec. reprod. Biol, 19, The effect of total umbilical cord occlusion upon maternal blood flow in the internal iliac and median uterine arteries was studied in eight chronically instrumented pregnant sheep. Occlusion of the umbilical cord was performed with an inflatable balloon occluder around the total cord. Blood flow was measured with electromagnetic flow transducers. Total umbilical cord occlusion of short duration (mean 40.1 s) caused a significant decrease in blood flow in the maternal internal iliac and median uterine arteries at the end of the occlusion to respectively 93.9% and 91.7% of the control values. The decrease in internal iliac and median uterine artery blood flow is attributed to an elevated fetal capillary pressure in the placenta, leading to an increased fetal placental tissue pressure which in turn compresses the maternal placental capillaries, resulting in a heightened vascular resistance and a decrease in uterine blood flow. umbilical cord occlusion; uterine blood flow Introduction Transient compression of the umbilical cord, recognizable by variable decelerations in the fetal heart rate pattern, often occurs during labor in the human. Cord compression has striking effects on fetal hemodynamics (De Haan et al., 1979; Evers et al., 1981) depending in severity upon the degree and the duration of the occlusion. Whether changes in pressure and flow in the umbilical circulation also affect maternal uterine hemodynamics is still controversial. It has been suggested that maternal vascular pressures in the ovine placenta directly affect fetal placental blood flow with sluice-flow characteristics (Power and Longo, 1973). This sluice-flow or placental waterfall concept has, on the other hand, been used to propose that changes in pressure and flow in the fetal placental vasculature may also influence the maternal placental circulation. In the studies by Berman et al. (1976) and Rudolph (1976) on this subject in sheep, however, no measurable effect of elevation of umbilical venous pressure or reduction of umbilical /85/$ Elsevier Science Publishers B.V

2 126 arterial pressure on uterine blood flow was found. Cottle et al. (1982), on the other hand, recently reported a depression of uterine blood flow in response to cord compression in sheep. We have investigated this aspect of the fetal maternal vascular relationship by analysing the effect of short-lasting total umbilical cord occlusion upon the blood flow in the maternal internal iliac and median uterine arteries. Materials and methods The experiments were carried out in eight pregnant sheep of the Dutch Texel breed. Surgical instrumentation was performed under aseptic conditions and under general anesthesia, induced with pentobarbitone and continued with 5% halothane in a 2 : 1 mixture of nitrous oxide and oxygen. In the last third of pregnancy (term 146 days) the uterus was exposed through a paramedian abdominal incision. A precalibrated electromagnetic flow transducer was placed around the median uterine artery on the ventrolateral side of the pregnant uterine horn. A small polyvinyl wing was attached to the cable of the flow transducer and this wing was secured to the uterine wall preventing movements of the flow transducer around the vessel and guaranteeing a perpendicular position to the vessel. Another electromagnetic flow transducer was placed around the maternal internal iliac artery after its point of origin from the common internal iliac artery. An inflatable balloon occluder was placed distal to both flow transducers for the assessment of zero blood flow. The fetal lambs were approached through a hysterotomy in the uterine wall lying over the fetal pelvis. They were provided with an inflatable balloon occluder around the total umbilical cord, an electromagnetic flow transducer around the intraabdominal common part of the umbilical veins and with catheters and electrodes for registration of arterial blood pressure, amniotic fluid pressure and fetal heart rate. Fetal blood pressure was measured in the descending aorta. All catheters and electrodes were exteriorized through a stab incision in the ewe s flank and protected in a pouch attached to the ewe s skin. Blood flow was measured with a Skalar Transflow 601 flowmeter system (Skalar, Delft, Holland). Fetal arterial blood pressure and amniotic fluid pressure were determined with pressure transducers with the zero point at the level of the ewe s spine. All signals were led to amplifiers (Helwett Packard 8800 series), displayed on a monitor and an eight-channel strip chart recorder and stored on magnetic tape. Antibiotics (ampicillin 1000 mg) were administered intravenously to the ewe before operation and also infused (ampicillin 500 mg) in the amniotic cavity during surgery. For the first 3 days postoperatively the mother received procaine penicillin ( IU) and dihydrostreptomycin (2000 mg) intramuscularly. The animals were allowed to recover for at least 3 days after surgery. Gestational age at the time of the experiments was 120 f 2.5 days (mean f S.D.; range days). The cord occlusions were performed 7.6 k 2.5 days (mean k S.D.; range 3-26 days) after surgery. All fetal and maternal variables were recorded for a control period of at least 30 min before experimentation was started. Total compression of the umbilical cord was performed by slowly injecting sterile saline solution into the inflatable balloon around the umbilical cord until no further filling could be achieved and the

3 127 umbilical venous flow as measured with the electromagnetic flow transducer was reduced to zero. Several occlusions were performed with intervals of at least 3-4.min between successive occlusions. The duration of the occ!usion time varied between 20 and 90 s, with a mean occlusion time of 40.1 k 3.3 s (mean k S.D.). A total number of 92 umbilical cord occlusions with simultaneous maternal flow measurements were performed in 8 animals. The maternal blood flow measurements were distributed as follows: the blood flow in the median uterine artery was measured during 69 cord occlusions in 7 animals. The blood flow in the internal iliac artery was also measured during 69 cord occlusions in 7 animals. Simultaneous measurement of the internal iliac artery blood flow as well as the blood flow in the median uterine artery was possible in 46 cord occlusions in 6 animals. The mean values of the blood flow in the internal iliac artery and/or the median uterine artery calculated over intervals of 10 s were pooled and statistically analysed. The control values (= C) were obtained from a period 10 s before the start of the occlusion. Control values were then compared with the mean values calculated from the last 10 s of the umbilical cord occlusion (= E), the interval 0 to 10 s after the ocilusion (7 lo), the interval 60 to 70 s after the occlusion (= 60) and finally with the mean value about 2 min after occlusion (= 120), calculated over the interval s after the occlusion. Data were expressed as percent change k S.E. with control values as the 100% reference level. Statistical analysis was done by means of Wilcoxon s matched-pairs signed-ranks test. All P values were calculated for twotailed tests. Results Maternal internal iliac artery blood flow during umbilical cord occlusion The blood flow in the maternal internal iliac artery was significantly (P < 0.001) reduced at the end of the occlusion to 93.9% of the control value (= 330 ml/mm). Internal iliac artery blood flow was also significantly (P < 0.001) less than the control value during the first 10 s after the end of the occlusion. The values at 60 and 120 s did not differ significantly from the control value. Table I shows the mean values k S.E. for the internal iliac artery blood flow expressed in percent change from control. TABLE I Maternal blood flow in the internal iliac artery during and after umbilical cord occlusion Mean f S.E., expressed as percent change from control. C = control: E = at the end of occlusion; 10 = during first 10 s after occlusion; 60 = after 1 min (interval s is used for calculation); 120 = after 2 min (interval s is used for calculation). C E (n = 69) (n = 69) (n = 69) (n=69) (n=69) Internal iliac artery * 1.1 a 94.8 f 1.1 a 97.5 f f 1.5 a P <

4 128 TABLE II Maternal blood flow in the median uterine artery during and after umbilical cord occlusion Mean + S.E., expressed as percent change from control. See also legend to Table I. C E (n = 69) (n = 69) (n = 69) (n = 69) (n = 69) Median uterine artery kl.l a 94.9 f 1.1 a 97.2 * f 1.5 a P i Maternal median uterine artery blood flow during umbilical cord occlusion The blood flow in the median uterine artery was significantly (P < 0.001) reduced at the end of the occlusion and the first 10 s after the end of the cord occlusion to respectively 91.7 and 94.9% of the control value (= 256 ml/min). A still-significant decrease (P < 0.05) in median uterine artery blood flow was found at 60 s after the end of the occlusion (97.2% of control value). Mean uterine blood flow at 120 s post occlusion did not differ significantly from the control value. Table II shows the mean values f SE. for the median uterine artery blood flow, expressed in percent change from control. Simultaneous measurement of maternal internal iliac artery and median uterine artery blood flow during umbilical cord occlusion The data of the blood flow changes in the internal iliac artery and median uterine artery during umbilical cord occlusion showed a greater reduction in median uterine iv._.-,/ b3.-.. : QUV 0.!_: (ML/MIN) QMUA (ML/MIN) QIIA (ML/M~N) , --_----., _ * 200 / *.- a.,--.,.---. / Oj _ -... /*---./ * *. 250 *-%,, , iv : b I TIME (SEC.) 0, I I \ Fig. 1. Changes in median uterine and internal iliac artery blood flows during an umbilical cord occlusion (- ). Data are expressed as mean * S.D. in intervals of 10 s. The gradual changes in QUV at the beginning and end of the occlusion are due to the way of graphic expression.

5 129 TABLE III Maternal blood flow as measured simultaneously in the internal iliac artery and the median uterine artery during and after umbilical cord occlusion Mean + SE., expressed as percent change from control. See also legend to Table I. P values are versus control. C E (n = 46) (n=46) (n = 46) (n = 46) (n = 46) Internal iliac artery 100*0 94.3k1.2a 96.8k1.3 b 97.5 f 1.5 d 98.4k1.8 Median uterine artery look0 93.6* 1.1 a 96.2 f 1.2 b 96.6* f 1.8 a P<O.OOl. b Pi C P i d P < artery blood flow than in the internal iliac artery flow. Part of the data of these two groups were, however, obtained from different experiments. Therefore the data on the maernal blood flow during cord occlusion were also analysed for the 46 occlusions in which internal iliac artery and median uterine artery blood flows were measured simultaneously in the same animals. The blood flow in the maternal internal iliac artery was significantly reduced at the end of the occlusion and during the first 10 s after the end of the cord occlusion to respectively 94.3% (P -C 0.001) and 96.8% (P < 0.01) of control value ( = 317 ml/mm). A still-significant (P < 0.05) decrease in internal iliac blood flow was found at 60 s post occlusion. Median uterine artery blood flow was also significantly reduced at the end of the occlusion and at the first 10 s after the end of the cord occlusion to respectively 93.6% (P < 0.001) and 96.2% (P < 0.01) of control value (= 236 ml/min). At 60 s post occlusion median uterine artery blood flow was still significantly (P -C 0.02) reduced to 96.6% of control value. The absolute values of the flow decreases were about the same in both vessels. Fig. 1 shows the mean values f S.D. calculated over intervals of 10 s of fetal umbilical blood flow and maternal internal iliac and median uterine artery blood flows in such an experiment. Table III shows the mean values k S.E. for both maternal blood flows expressed in percent change from control. Discussion The results from this study show that the maternal blood flow to the uterus is depressed during umbilical cord occlusion of short duration. The most likely explanation of the decrease in internal iliac and median uterine artery blood flows during umbilical cord occlusion is an increased pressure in the fetal placental tissue leading to a decreased maternal flow by elevating the resistance in the maternal uterine circulation. An increase in tissue pressure and possibly tissue fluid formation could develop during the umbilical cord occlusions as follows: the umbilical veins will first be compressed during inflation of the balloon occluder. After a lag time of several seconds, necessary for the complete filling of the balloon, the umbilical arteries are occluded too. During this lag time the umbilical veins are completely compressed while the umbilical arteries are still totally or partially patent. A certain

6 130 additional amount of arterial blood will then be pumped into the umbilical circulation and will eventually be trapped in the umbilical vascular bed after complete compression of the umbilical arteries. The elevated fetal capillary pressure in the placenta may then lead to an increased fetal placental tissue pressure which in turn compresses the maternal placental capillaries, resulting in an increased vascular resistance and a decrease in uterine blood flow. The umbilical placental circulation is capable of storing an extra amount of blood, which is shown in the study by de Haan et al. (1979), who found that during selective occlusion of both umbilical veins a slowly decreasing mean flow can be measured in the umbilical arteries during the first seconds following the start of the occlusion. The results of a study by Jongsma et al. (1979), in which an increase in placental blood volume of 34.8 ml after clamping of the umbilical veins was found, are in favor of this hypothesis. The results from this study are in agreement with the report by Cottle et al. (1982), who also found a decrease in the median uterine artery blood flow during long-lasting (4 min) partial umbilical cord occlusion, which effect they ascribed to an increased tissue fluid pressure in the placenta. Cottle et al. furthermore suggested that fetal catecholamines released from the fetal adrenal medulla in response to hypoxemia (Comline et al., 1965; Jones and Robinson, 1975) and crossing the placental barrier might be in part responsible for the reduced uterine blood flow during umbilical cord occlusion. In a recent study (Cottle et al., 1983), however, evidence was found that fetal catecholamines released in response to the hypoxemia caused by umbilical cord occusion were not the major determinant of the uterine blood flow reductions induced by cord occlusions. They observed the same reductions in uterine blood flow during umbilical cord occlusion with and without the previous administration of promazine (an alpha-adrenergic blocker) to the ewe. If the reduction in maternal uterine blood flow during umbilical cord occlusion were mainly due to fetal catecholamines, then this reduction in flow should have been absent after maternal alpha-adrenergic blockade, which was not the case. The results of the present study also give evidence that fetal catecholamines are not primarily involved in the mechanism of maternal flow reduction. Total umbilical cord occlusion virtually reduces umbilical blood flow to zero, thereby preventing access of fetal catecholamines to the placental barrier. Furthermore, one would have expected a sustained reduction in maternal uterine blood flow after the end of the cord occlusion, because of the relatively long-lasting uterine vasoconstriction after alphaadrenergic receptor stimulation. Another possible explanation for the change in maternal uterine blood flow might be the local production of vasoactive substances involved in the adjustment of maternal and fetal flow ratios. The existence of a chemical link between mother and fetus was suggested by Rankin and McLaughlin (1979), and several vasoactive prostanoids and eicosanoids might be considered candidates. Although the small degree of uterine flow decrease suggests that an increased turgor in the fetal cotyledonary tissue is most likely, the involvement of locally produced vasoactive substances cannot be discounted at this time. The greater decrease in median uterine artery blood flow compared to internal iliac artery blood flow found in our study was in terms of percentage changes. The flow decrease in absolute values was the same in both vessels. The difference in per-

7 131 centage change between the two vessels is explained by the higher absolute flow in the internal iliac artery, part of which blood flow is to non-uterine structures which should not show any change in blood flow during umbilical cord occlusion. It also makes clear why no changes in uterine blood flow during umbilical cord occlusion were found in the study by Berman et al. (1976). They measured the maternal blood flow in the middle sacral artery, also known as the common internal iliac artery. This vessel not only supplies the pregnant uterine horn but also the non-pregnant uterine horn, the presacral region and other structures (Fuller et al., 1975). It is conceivable that relatively small decreases in the blood flow in a part of the vascular bed of this artery do not lead to statistically significant changes in the blood flow of the common internal iliac artery, in which vessel the blood flow is much higher than in the median uterine artery. Another possibility might be that a relatively small increase in the resistance to flow in a part of the vascular bed of this artery might result in shifting flow to other vessels to such a degree that the total flow in the trunk vessel is not affected. Acknowledgements The authors express their gratitude to Petra Rommers, May Bost, Jet Beekman and Ruud Kruger for their technical assistance. References Berman, W., Jr., Goodlin, R.C., Heymann, M.A. and Rudolph, A.M. (1976): Relationship between pressure and flow in the umbilical and uterine circulation of the sheep. Circulat. Res., 38, 262. Comline, R.S., Silver, LA. and Silver, M. (1965): Factors responsible for the stimulation of the adrendl medulla during asphyxia in the foetal lamb. J. Physiol., 178, 211. Cottle, M.K.W., Van Petten, G.R. and Van Muyden, P. (1982): Depression of uterine blood flow in response to cord compression in sheep. Can. J. Physiol. Pharmacol., 60, 825. Cottle, M.K.W., Van Petten, G.R. and Van Muyden, P. (1983): Maternal and fetal cardiovascular indices during fetal hypoxia due to cord compression in chronically cannulated sheep. II. Responses to promazine. Amer. J. Obstet. Gynec., 146, 686. Evers, J.L.H., De Haan, J., Jongsma, H.W., Crevels, A.J., Arts, T.H.M. and Martin, C.B., Jr. (1981): The preejection period of the fetal cardiac cycle. I. Umbilical cord occlusions. Europ. J. Obstet. Gynec. reprod. Biol. 11, 401. Fuller, E.O., Galetti, P.M. and Tachenchi, T. (1975): Major and collateral components of blood flow to the pregnant sheep uterus. Amer. J. Physiol., 229, 272. De Haan, J., Martin, C.B., Evers, J.L.H. and Jongsma, H.W. (1979): Pathophysiologic mechanisms underlying fetal heart rate patterns. In: Perinatal Medicine, pp Editors: Thalhammer, O., Baumgarten, K. and Pollak, A. George Thieme, Stuttgart. Jones, C.T. and Robinson, R.O. (1975): Plasma caecholamines in foetal and adult sheep. J. Physiol., 248, 15. Jongsma, H.W., Evers, J.L.H., Huikeshoven, F.J.M., De Haan, J. and Martin, C.B. (1979): Compliance and flow resistance of the umbilical circulation in vivo in sheep and effects on circulatory parameters. Society for Gynecologic Investigation. Abstract No. 45, San Diego. Power, G.G. and Longo, L.D. (1973): Sluice flow in placenta: maternal vascular pressure effects on fetal circulation. Amer. J. Physiol., 225/6, Rankin, J.H.G. and McLaughlin, M.K. (1979): The regulation of the placental blood flows. J. dev. Physiol., 1, 3. Rudolph, A.M. (1976): Factors affecting umbilical blood flow in the lamb in utero. In: Perinatal Medicine, pp Editors: G. Rooth and L.E. Matteby. Almquist and Wiksell Int., Stockholm.