Fetoplacental vascular responses to prostacyclin after thromboxane-induced vasoconstriction

The vasodilator prostacyclin is produced by fetal tissues and may serve to protect umbilical blood flow. We hypothesized that prostacyclin could reverse fetoplacental vasoconstriction produced by a thromboxane mimic (U-46619). Fetal regional blood flow was measured by the radioactive microsphere technique in six unanesthetized, near-term ovine fetuses. Measurements were made in the control period, again 20 minutes after a fetal infusion of U-46619 was begun, and finally 20 minutes after prostacyclin was added to the U-46619 infusion. Mean arterial pressure rose significantly in response to U-46619 (38 +/- 1 to 51 +/- 2 mm Hg, p less than 0.01) and returned to baseline after prostacyclin (42 +/- 2 mm Hg). Renal resistance was increased from 0.16 +/- 0.01 to 0.22 +/- 0.01 mm Hg.ml-1.min.100 gm-1 (p less than 0.05) by U-46619 and decreased significantly (p less than 0.05) below baseline by addition of prostacyclin (0.10 +/- 0.02 mm Hg.ml-1.min.100 gm-1). Placental resistance also increased significantly (p less than 0.03) in response to U-46619 (from 0.15 +/- 0.01 to 0.21 +/- 0.01 mm Hg.ml-1.min.kg-1 fetal weight) but was further increased to 0.29 +/- 0.03 mm Hg.ml-1.min.kg-1 fetal weight by the addition of prostacyclin. Umbilical placental blood flow decreased significantly (p less than 0.03) when prostacyclin was added to U-46619 (315 +/- 40 to 195 +/- 30 ml.min-1.kg-1 fetal weight). Whereas U-46619 had no effect on fetal arterial blood gases, the addition of prostacyclin resulted in significant fetal acidosis (p less than 0.03). We conclude that thromboxane mimic causes fetal hypertension and renal and placental vasoconstriction. Prostacyclin reverses hypertension and renal vasoconstriction but, unexpectedly, worsens fetal placental vasoconstriction produced by thromboxane. It is likely that the observed fetal acidosis is a result of compromised placental function.     

Ovine placental vascular response to the local application of prostacyclin

Rankin et al. have shown that prostacyclin does not dilate the ovine placenta, yet Clark et al. have shown that retrograde infusion of prostacyclin dilates the uterine vasculature. To determine the effects of prostacyclin on the sheep placenta, the two groups have collaborated. In five chronically catheterized near-term sheep, blood flows were measured by the radioactive microsphere technique. Control blood flows were measured and prostacyclin infused into the retrograde uterine artery catheter at 10 micrograms/min. The blood flows were again measured, and the area served by the catheter was then delineated by the injection of a green dye at the time of maternal euthanasia. The placenta and cotyledons were separated and the kidneys were obtained for assay. The systemic effects of prostacyclin were minimal and have been observed previously. The resistance of the myometrium fell from 566 +/- 99.9 to 322 +/- 63.9 mm Hg X ml-1 X min X gm (p less than 0.002). The placental tissue showed no change in resistance. When the tissues were combined, we observed a decrease in resistance from 0.38 +/- 0.18 to 0.32 +/- 0.14 mm Hg X ml-1 X min (p less than 0.004), thereby confirming the observation that there was indeed vasodilation downstream. However, the vasodilation was not in the placenta but in the myometrium, and we reconfirm our previous conclusion that prostacyclin does not dilate the sheep placenta.     

Placental vascular responses to nicardipine in the hypertensive ewe

Calcium channel blockers are arterial vasodilators effective in the treatment of hypertension. Therefore nicardipine, a dihydropyridine calcium channel blocker, should modulate angiotensin II-induced vasoconstriction. Regional blood flows were measured with radioactive microspheres in five chronically catheterized near-term ewes both before and 15 minutes after maternal infusion of angiotensin II at 5 micrograms/min. Nicardipine was then administered intravenously at 20 micrograms/kg/min over 2 minutes while the angiotensin II infusion was maintained. Blood flows were measured after 5 minutes. Maternal blood pressure levels were increased by angiotensin II from 83 +/- 4 mm Hg to 114 +/- 5 mm Hg, and were decreased to 70 +/- 4 mm Hg by nicardipine (p less than 0.05). Nicardipine also reversed angiotensin II-induced vasoconstriction in the renal and endomyometrial vascular beds (p less than 0.05). Unexpectedly, however, nicardipine worsened placental vasoconstriction caused by angiotensin II, as placental blood flow fell from 242 +/- 32 ml.min-1.kg-1 fetal weight to 128 +/- 7 ml.min-1.kg-1 fetal weight (p less than 0.05), and placental resistance increased from 0.48 +/- 0.04 mm Hg.ml-1.min.kg-1 fetal weight to 0.55 +/- 0.05 mm Hg.ml-1.min.kg-1 fetal weight (p less than 0.05). Nicardipine reverses angiotensin II-induced vasoconstriction systemically and in the kidney and uterus of the pregnant ewe, but does not reverse placental vasoconstriction and may significantly alter fetal cardiorespiratory status.     

Transplacental, amniotic, urinary, and fetal fluid dynamics during very-large-volume fetal intravenous infusions

With rapid intravenous infusion of very large volumes of isotonic saline solutions into the fetus, the fluid could stay within the fetal body, thereby creating hydrops fetalis, be transferred into the amniotic fluid through the fetal kidneys, thereby creating polyhydramnios, or be transferred across the placenta into the maternal circulation. This study was designed to explore these possibilities. After a 1-hour control period, 10 near-term chronically catheterized ovine fetuses were infused intravenously with 4 L (greater than 100% of fetal weight) of either isotonic saline solution or lactated Ringer's solution over 4 hours. Fetal arterial pressure was significantly elevated by 7 mm Hg throughout the infusion (p less than 0.00001). Venous pressure underwent a transient rise (4.8 mm Hg) at 20 minutes of infusion and remained elevated (2.7 mm Hg) during the rest of the infusion (p less than 0.00001). Fetal urine flow increased by an average of 5.7 +/- 0.4 ml/min throughout the infusion (p less than 0.00001) and accounted for 34.1% +/- 2.6% of the infused volume. Estimated fetal extracellular fluid volume increased by 17.7% +/- 1.8% of the infused volume. Because fetal fluid retention, urine flow, and amniotic fluid volume changes accounted for only half of the infused fluid, the remainder of the infused volume must have crossed the placenta and entered the maternal circulation. Given the above changes in vascular pressures, this requires a filtration coefficient of the placenta 50 to 100 times the previously reported values. Thus we conclude that relatively small changes in fetal vascular pressures dramatically alter the filtration capacity of the ovine placenta and transplacental volume flow.     

Fetal responses to maternal infusions of angiotensin II

It is unclear whether the fetus is affected by maternal infusions of angiotensin II; therefore we studied maternal and fetal responses (n = 9) to angiotensin II (1.15, 2.29, 11.5 micrograms/min) infused 5 minutes into the vena cava of chronically instrumented sheep (129 to 137 days of gestation) while monitoring PO2, PCO2, pH, heart rate, uterine blood flow, and arterial and umbilical venous pressures. Pregnant sheep demonstrated expected dose-related increases in mean arterial pressure and decreases in uterine blood flow (p less than 0.05). Increases in fetal mean arterial pressure also correlated with the maternal dose of angiotensin II (r = 0.77, p less than 0.001). Fetal heart rate appeared to increase with 2.29 micrograms/min; however, bradycardia was observed with 11.5 micrograms/min (p less than 0.05) and was associated with decreased PaO2, 19.0 +/- 1.0 to 14.3 +/- 1.4 mm Hg (p less than 0.05), increased PaO2 (p less than 0.05), and decreased umbilical venous PO2, 31.4 +/- 2.3 to 27.0 +/- 1.9 mm Hg. The decreases in PO2 correlated with decreases in uterine blood flow (r = 0.60, p less than 0.002, and r = 0.75, p less than 0.005, respectively). Nevertheless, changes in fetal mean arterial pressure also occurred in the absence of altered fetal oxygenation; thus decreased uterine blood flow and fetal oxygenation alone cannot explain the fetal cardiovascular responses. It is suggested that angiotensin II or an active metabolite may cross the ovine placenta.     

The effect of prostacyclin on angiotensin II-induced placental vasoconstriction

Significant alterations in vascular responsiveness to angiotensin II have been documented during pregnancy. We have observed that prostacyclin, a potent vasodilating prostaglandin, does not dilate the ovine placental vasculature. However, we thought it might modulate the placental vasoconstriction produced by angiotensin II. Regional blood flows and resistances were measured by the radioactive microsphere technique in six near-term sheep. Blood flows were measured in the control condition and 15 minutes after beginning an infusion of angiotensin II at 5 micrograms/min (T1). Additional measurements were made 15 minutes after the addition of 50 micrograms/min of prostacyclin to the angiotensin II infusate (T2) and 15 minutes after withdrawing prostacyclin from the angiotensin II infusion (T3). Mean arterial pressure rose in response to angiotensin II and decreased significantly with prostacyclin administration. The renal and uterine nonplacental vascular beds showed the expected vasoconstriction in response to angiotensin II, which was then reversed to control levels by prostacyclin infusion. Unexpectedly, prostacyclin did not reverse the angiotensin II vasoconstriction in the placenta but further increased resistance (p less than 0.03). Placental resistance changed from 0.33 +/- 0.04 peripheral resistance units in the control condition to 0.42 +/- 0.06 peripheral resistance units for T1 (p less than 0.03), and prostacyclin infusion further increased placental resistance to 0.63 +/- 0.10 peripheral resistance units for T2 (p less than 0.03). We conclude that the placental vascular response to prostacyclin is different from that of other organs and that prostacyclin does not dilate, but further constricts the placenta in the near-term sheep with angiotensin II-induced systemic vasoconstriction.     

Urinary and cardiovascular responses to indomethacin infusion in the ovine fetus.

OBJECTIVE: Our objective was to explore the urinary and cardiovascular responses of the near-term ovine fetus to plasma indomethacin levels similar to those in the human neonate undergoing indomethacin therapy. STUDY DESIGN: Chronically catheterized ovine fetuses between 125 and 139 days of gestation were studied. After a 1-hour control period we gave a bolus of 0.35 mg/kg estimated fetal weight of indomethacin into a fetal vein, followed by a 0.017 mg/kg/min continuous infusion for 5 hours (n = 9). Results were compared with a vehicle-infusion-only group (n = 10). RESULTS: During the first 3 hours of indomethacin infusion, fetal urinary output was increased by an average of 84.9% +/- 55.6% (analysis of variance, p less than 0.01). Urinary osmolality and sodium and chloride concentrations underwent sustained increases throughout the infusion period (p less than 0.001). Sodium excretion increased by 212% +/- 111% (p less than 0.05). Fetal arterial and venous pressures increased (p less than 0.001), and the change in urinary flow correlated positively with the change in arterial pressure (R = 0.55, p = 0.014). Fetal heart rate increased by 10% +/- 4% 1 hour after the bolus and remained elevated throughout the remainder of the infusion relative to vehicle-infused animals (p less than 0.001). Vehicle infusion had no effect on any fetal variable. CONCLUSIONS: This study does not support the hypothesis that indomethacin acutely reduces urinary flow rate in the late-gestation ovine fetus. Further, the observed urinary flow increases may be mediated in part by a pressure diuresis.     

Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.     

The effect of mild hypoxemia maintained for twenty-four hours on maternal and fetal glucose, lactate, cortisol, and arginine vasopressin in pregnant sheep at 122 to 139 days' gestation

The effects of prolonged mild hypoxemia on the fetus have received little attention. We investigated the response to a decrease in fetal arterial Po2 of 5 mm Hg or less sustained for a period of 24 hours in the chronically instrumented fetal lamb. Hypoxemia was induced by an infusion of nitrogen via the maternal trachea for 24 hours in 13 pregnant sheep at 122 to 139 days' gestation. Two control periods of air infusion via the maternal trachea for 24 hours were alternated with hypoxemia. Fetal hypoxemia was not associated with any change in fetal pH. During the first and second exposures to hypoxemia, there was an increase in fetal plasma lactate of 22.8 +/- 22.3 and 15.3 +/- 14.6 mg.dl-1 (mean +/- SD) above preliminary values (p less than 0.05) compared with the control period. Fetal plasma cortisol also increased by 5.7 +/- 6.1 and 9.5 +/- 5.4 ng.ml-1 (mean +/- SD) (p less than 0.05) compared with the control period. These results suggest that the fetal lamb at 122 to 139 days' gestation is highly sensitive to small decrements in Po2 of 5 mm Hg or less.     

Effects of intravenous terbutaline on maternal circulation and fetal heart activity

The effects of terbutaline on maternal circulation and fetal heart activity were studied in 15 healthy pregnant women admitted for external cephalic version. The two-step infusion of terbutaline (5-10 micrograms/min) resulted in increases in maternal heart rate (p less than 0.001), cardiac output (p less than 0.001), systolic arterial pressure (p less than 0.001) and pulse pressure (p less than 0.001), while diastolic arterial pressure (p less than 0.001) and total peripheral vascular resistance (p less than 0.001) were reduced. Mean arterial pressure was unchanged after the infusion. Fetal heart activity assessed by cardiotocography showed a gradual increase in baseline fetal heart rate (p less than 0.01) and an increased percentage acceleration time (p less than 0.05). Fetal movements also increased during the infusion (p less than 0.05). The terbutaline infusion had a positive inotropic effect and produced decreased systemic vascular resistance in the pregnant woman, and placental transfer of the drug resulted in increased fetal heart activity. The potential influence of the drug-induced changes in maternal hemodynamics on utero-placental perfusion require further investigation.     

Fetal cardiorespiratory changes during spontaneous prelabor uterine contractions in sheep

Fetal cardiorespiratory changes during spontaneous prelabor uterine contractions (called contractures) were studied in 12 chronically catheterized fetal sheep at 120 to 143 days' gestation. During contractures the carcass blood flow increased significantly from 27 +/- 2 (SEM) to 32 +/- 3 ml/min/100 gm. There were no significant changes in combined ventricular output or in blood flow to the umbilical circulation, brain, heart, adrenal glands, gut, kidney, and lung. Fetal arterial blood pressure increased from 57 +/- 2 to 62 +/- 1 mm Hg (p less than 0.001) during contractions. There were no significant changes in fetal heart rate. In the fetal femoral artery during contractures the oxygen content decreased from 6.1 +/- 0.2 to 5.4 +/- 0.2 ml/dl of blood (p less than 0.001), and carbon dioxide tension increased significantly from 44 +/- 0.4 to 45 +/- 0.4 mm Hg (p less than 0.001). The pH did not change. The increase in carcass blood flow during contractures suggests that there was an increase in fetal skeletal muscular activity or tone. An increase in fetal skeletal muscle activity, together with a decrease in uterine blood flow could explain the small decrease in fetal oxygen content that occurs with each contracture. Fetal compression and/or changes from rapid eye movement to synchronized sleep or arousal observed during contractures are possible stimuli causing increased fetal skeletal muscle tone or activity. Since contractures periodically result in neuromuscular activity in the fetus in its protected fluid-filled environment, they may play a key role in fetal neuromuscular development by stimulating "exercising" in the fetus in utero.     

Placental vascular responses to 6-keto-prostaglandin E1 in the near-term sheep

6-Keto-prostaglandin E1 (6-keto-PGE1) is a biologically active, stable metabolite of prostaglandin I2 (PGI2). It has vasoactive properties similar to those of PGI2 and it has been shown to decrease the resistance of the renal, mesenteric, and pulmonary vascular beds. PGI2 is synthesized by the pregnant uterus and is vasoactive in the ovine placenta. The effects of 6-keto-PGE1 on uterine and placental blood flow in pregnant ewes were determined for comparison with those of PGI2. Near-term ewes and their fetuses were chronically catheterized to permit the measurement of regional blood flow by the radioactive microsphere method. In six sheep a 5-minute maternal jugular infusion of 3.25 micrograms/kg/min of 6-keto-PGE1 decreased mean arterial blood pressure from 89 +/- 4.8 to 63 +/- 7.1 mm Hg. Uterine vascular resistance decreased from 0.55 +/- 0.11 to 0.35 +/- 0.05 peripheral resistance units (PRU), but maternal cotyledonary resistance increased from 0.19 +/- 0.04 to 0.27 +/- 0.03 PRU. In five sheep a fetal intravenous infusion of 18 micrograms/min of 6-keto-PGE1 decreased mean fetal blood pressure from 43 +/- 2 to 29 +/- 2 mm Hg. Cotyledonary vascular resistance increased from 0.30 +/- 0.02 to 0.55 +/- 0.09 PRU . kg-1. In these sheep there were no significant changes in maternal uterine, renal, or cotyledonary blood flows. These results indicate that 6-keto-PGE1 is similar to PGI2 in that it produces maternal cotyledonary vasoconstriction, hypotension, and vasodilation in other organs.     

Intravenous clonidine hydrochloride toxicity in pregnant ewes

Administration of intravenous clonidine hydrochloride has been advocated to rapidly control blood pressure in severe preeclampsia. To examine clonidine's acute maternal and fetal effects were intravenously injected 300 micrograms clonidine in eight chronically prepared normotensive near term ewes. Unlike intravenous saline solution injection, clonidine produced significant toxicity--intraamniotic pressure increased 97 +/- 27% (p less than 0.05), uterine blood flow decreased 55 +/- 7% (p less than 0.001), maternal and fetal serum glucose increased 158 +/- 23% and 249 +/- 91%, respectively (p less than 0.001), and maternal and fetal Po2 decreased to 44 mm Hg +/- 4 mm Hg and 13 mm Hg +/- 1 mm Hg, respectively (p less than 0.05). Maternal and fetal blood pressure and serum cortisol were unaffected by clonidine, whereas heart rate decreased. No adverse maternal or fetal effects were noted with serum clonidine concentrations less than 1.0 ng/ml. Direct fetal infusion of clonidine did not lower fetal arterial Po2 levels, although heart rates decreased and serum glucose levels increased. The multiple effects of clonidine infusion are best explained by actions on alpha 2-adrenergic receptors. These results suggest that intravenous administration of clonidine may adversely affect the fetus by direct actions and by alterations in maternal physiology.     

Contribution of the Bohr effect to the fall in fetal PO2 caused by maternal alkalosis

A decrease in the PO2 of fetal arterial blood is observed in maternal alkalosis caused by hyperventilation in labour or exercise. The contribution of altered blood oxygen affinity to this effect was studied experimentally and by computer simulation of placental gas exchange. Thirteen guinea pigs near term of pregnancy were anesthetized and the right atrium of the fetus was catheterized to enable continuous and simultaneous measurement of PO2 and PCO2 by mass spectrometry. An infusion of base was given through a catheter in the descending aorta of the dam and the effect on fetal respiratory gas tensions observed. The mean change in maternal arterial pH measured in blood taken from a femoral artery was 0.07 +/- 0.04 (mean +/- S. D.). There was an immediate decrease in PO2 in the right atrium of the fetus, but no consistent alteration in PCO2. Two minutes after the start of the infusion, PO2 had fallen by 3.2 +/- 1.6 Torr (p less than 0.001) and PCO2 had risen by 1.7 +/- 1.8 Torr (not significant). The experiments were simulated using a mathematical model of placental gas exchange in the guinea pig. The model was able to predict the change in fetal arterial PO2, given numerical values for the pH, PO2 and PCO2 of fetal and maternal arterial blood prior to infusion of base and for maternal blood during the infusion of base. These values were obtained from the experimental data. Other input variables of the model were maternal and fetal hematocrit and DPG concentration, and the rates of blood flow on the two sides of the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)     

Umbilical artery pulsatility index and placental vascular resistance during acute hypoxemia in fetal lambs

The effect of hypoxemia on the pulsatility index (PI) of the umbilical artery flow velocity waveform and placental vascular resistance was studied. Fetal hypoxemia was induced by maternal breathing of a low-oxygen gas mixture. Umbilical venous blood flow was measured with an electromagnetic flowmeter. Placental vascular resistance (PVR) was defined as the ratio perfusion pressure (mean arterial pressure minus umbilical venous pressure) and umbilical blood flow. Umbilical artery velocity waveforms were obtained by a 5-MHz pulsed Doppler device around one umbilical artery in 4 lambs and by a transcutaneous 4-MHz continuous wave Doppler transducer in 3 lambs. Fetal arterial oxygen content was lowered from 2.28 +/- 0.18 to 0.93 +/- 0.15 mM (p less than 0.05), while pCO2 and pH remained unchanged. Control values of the hemodynamic variables were compared with values during deepest hypoxemia. Fetal heart rate, mean arterial and umbilical venous pressure, PVR and the umbilical artery PI did not significantly change, whereas umbilical blood flow increased from 436 +/- 64.7 to 491 +/- 65.9 ml/min (p less than 0.05) during deepest hypoxemia. Individual regression analysis, however, showed a significant inverse correlation of umbilical venous pressure whereas PVR had a positive correlation with actual oxygen content. It is concluded that acute fetal hypoxemia slightly decreases PVR, but does not affect the umbilical artery PI in sheep. Decreasing fetal oxygenation is associated with an increase in pressure in the umbilical vein.     

Effect of magnesium on cocaine-induced, catecholamine-mediated platelet and vascular response in term pregnant ewes

Ten pregnant ewes were alternated in a study of the blocking effect of parenteral magnesium on the catecholamine response to cocaine. Indirect blood pressures were recorded at 1-minute intervals for 12 minutes before and after a bolus of 2 mg/kg of cocaine. Fetal heart rates were continuously recorded from skin electrodes. Platelet counts were performed before and 12 minutes after cocaine. Control ewes received lactated Ringer's solution, and test animals had 5 mg/kg of elemental magnesium in the form of MgSO4-7H2O in a rapid infusion. A semicrossover was also performed. Platelet counts fell precipitately in controls and rose after magnesium infusions. Fetal heart rates rose in controls at 5-minute intervals and were unchanged in magnesium-treated mothers. Because of disparity of the baseline mean arterial pressure, direct comparisons were not significant before and after cocaine. Alterations from the baseline were different in magnesium-treated versus control animals, with values in the latter rising by 28 +/- 10 mm Hg with lactated Ringer's solution plus cocaine and falling by 3 +/- 5 mm Hg with magnesium pretreatment. Values in test animals originally treated with magnesium rose 4 +/- 11 mm Hg for an overall significance of p less than 0.05. Low beginning serum magnesium levels were associated with ovine hypertension and reduced fetal weight and survival.     

The effect of fetal sepsis on umbilical cord blood gases.

The relationship between fetal sepsis and acid-base status is unknown. We hypothesized that in utero sepsis would result in fetal metabolic acidemia. In a retrospective study during a 38-month period, the acid-base status at birth of neonates with in utero sepsis, documented by positive blood cultures, was reviewed. Compared with term neonates, preterm neonates had a 22-fold increase in the risk of bacteremia at birth. In spite of this increased risk of sepsis, there was no significant alteration in arterial pH in preterm septic neonates when compared with preterm controls. Fetal sepsis at term was accompanied by a statistically significant reduction in arterial pH (7.21 +/- 0.07) compared with controls (7.26 +/- 0.06, p less than 0.05). When controlled for other variables, the decrease in arterial pH at term was correlated with an increased duration of labor (7.3 +/- 0.7 in controls vs 10.8 +/- 0.9 hours in neonates with sepsis, p less than 0.05). The classic predictors of chorioamnionitis were found to be poor prognostic indicators of fetal bacteremia. Fetal sepsis at term is associated with a deterioration in the fetal acid-base status and a prolongation of labor.     

Dose-response curves of the uterine and placental vascular beds to prostaglandin I2

Local infusion of prostaglandin I2 (PGI2) has been reported to dilate the uteroplacental vasculature in a dose-dependent manner. In this experiment we attempted to distinguish the placental and nonplacental (uterine) components of this response over four concentrations of PGI2. Eleven near-term sheep were chronically instrumented for determination of regional blood flows by the use of radioactive microspheres. PGI2 was administered in a retrograde manner via a branch of the middle uterine artery at 1, 3, 10, and 20 micrograms/min. Flows were measured before (control) and after 5-minute infusions at each of the four concentrations (test). The uterine vasculature vasodilated in response to local PGI2 infusion. The 10 micrograms/min dose, for example, produced a mean (+/- SEM) flow of 0.70 +/- 0.07 ml/min/gm; the control value was 0.41 +/- 0.03 ml/min/gm (p less than 0.001). At 20 micrograms/min the test and control flows were 0.75 +/- 0.16 and 0.36 +/- 0.06 ml/min/gm (p less than 0.05), respectively. Uterine vascular resistance fell in a dose-dependent manner as well. There was no evidence of placental vasodilation at any of the doses tested. Renal vasodilation and decreased systemic arterial pressure at higher PGI2 doses suggest a recirculation effect. We conclude that PGI2 does not dilate the placental vasculature over the dose range of 1 to 20 micrograms/min and that the reported vasodilation of the uteroplacental vasculature is a result of decreased resistance in the uterine vasculature alone.     

Persistent sucrose stimulation of ovine fetal ingestion: lack of adaptation responses.

OBJECTIVE: Sweet taste responsiveness is reduced in adult rats and humans following continued oral sucrose. We have previously demonstrated that sublingual sucrose stimulates near term ovine fetal swallowing, suggesting intact taste responsiveness. We sought to determine if prolonged oral sucrose infusion to the near term ovine fetus will evoke adaptation, as manifested by reduced swallowing stimulation. METHODS: Time-dated pregnant ewes and fetuses (n = 4) were chronically prepared with fetal vascular and sublingual catheters, and electrocorticogram and esophageal electromyogram electrodes and studied at 129 +/- 1 d gestation. Following an initial 2 h basal period, sucrose (2.5%) was infused sublingually (0.25 ml/min) to the fetus for 8 h. Fetal swallowing activity, blood pressure and heart rate were continuously recorded while maternal and fetal arterial blood samples were taken at timed intervals. RESULTS: During the basal period, fetal swallowing averaged 0.9 +/- 0.1 swallows/min. Fetal swallowing increased significantly following sublingual 2.5% sucrose infusion and remained significantly elevated at 2, 4, 6 and 8 h after initiation of sucrose infusion (1.3 +/- 0.1, 1.2 +/- 0.1, 1.3 +/- 0.1, 1.3 +/- 0.1 swallows/min; p < 0.001). There were no significant changes in fetal cardiovascular or arterial blood parameters. CONCLUSIONS: Although oral sucrose significantly stimulates near term ovine fetal ingestive behavior, sweet taste adaptation or habituation does not occur, in contrast to that observed in adult animals and human. The lack of taste adaptation in the fetus/newborn may facilitate increased neonatal food intake and accelerated growth.     

Indomethacin-induced urinary flow rate reduction in the ovine fetus is associated with reduced free water clearance and elevated plasma arginine vasopressin levels.

OBJECTIVE: The purpose of our study was to explore the urinary responses of the ovine fetus to indomethacin levels comparable with those used therapeutically in the human fetus. STUDY DESIGN: After a 1-hour control period, chronically catheterized ovine fetuses between 125 and 139 days of gestation were given an intravenous bolus of indomethacin (0.05 mg/kg estimated fetal weight) followed by a 0.0025 mg/kg/min continuous infusion for 5 hours. The experimental group (n = 9) was compared with a vehicle-only infusion group (n = 10). RESULTS: There was a sustained 55.7% +/- 9.5% (mean +/- SEM) decrease in urinary output by 2 hours of indomethacin infusion (p < 0.00001, analysis of variance). Urinary osmolality, potassium, and chloride concentrations underwent sustained increases during the infusion period (p < 0.005). Free water clearance decreased by 67.5% +/- 12.0% (p < 0.001). Fetal arterial pressure increased only transiently (p < 0.05), and increases in venous pressure (p = 0.013) and heart rate (p < 0.0001) were sustained. Fetal plasma arginine vasopressin concentration increased during indomethacin infusion (p < 0.05) and was correlated with the fall in urinary flow rate and free water clearance (p = 0.002). During vehicle infusion no significant changes were observed in any of the variables. CONCLUSIONS: Our data indicate that the fetus undergoes antidiuresis when exposed to low levels of indomethacin and that the observed antidiuresis is mediated by a decrease in free water clearance. The reduction in free water clearance may be mediated by increases in plasma arginine vasopressin concentrations.