Effects of calcium entry blocker (nicardipine) tocolysis in rhesus macaques: fetal plasma concentrations and cardiorespiratory changes

Tocolytic doses of nicardipine, a dihydropyridine calcium entry blocker, were administered to chronically catheterized rhesus monkeys between days 128 and 132 of gestation. During periods of spontaneous uterine contractility, a 500 micrograms nicardipine bolus was injected intravenously, and this was followed by continuous infusion (6 micrograms/kg/min) to the mother for 1 hour. Uterine activity (amniotic fluid pressure) and maternal heart rate and blood pressure were monitored continuously. Paired maternal and fetal blood samples were drawn at frequent intervals to monitor pH, PO2, PCO2, and plasma nicardipine concentrations. Peak maternal nicardipine concentrations ranged from 175 to 865 ng/ml while peak fetal levels ranged from 7 to 35 ng/ml. Fetal heart rate and blood pressure were unaffected. However, fetuses became acidotic (pH 7.26 +/- 0.01 versus 7.33 +/- 0.01) and hypoxemic (PO2 16.0 +/- 3.2 versus 24.5 +/- 2.0 mm Hg) after maternal nicardipine treatment (p less than 0.01). Despite the fact that maternal nicardipine treatment exerted a significant tocolytic effect, the undesirable fetal side effects are of concern and deserve further investigation.     

Fetal vascular responses to maternal nicardipine administration in the hypertensive ewe

Calcium channel blockers such as nicardipine act as arterial vasodilators and are effective in the treatment of hypertension. Although they are also effective tocolytic agents, fetal effects have not been fully studied. Fifteen chronically catheterized near-term ewes were studied. Maternal and fetal cardiorespiratory parameters were measured in the control period and again 15 minutes after maternal venous infusion of angiotensin II. Nicardipine 20 micrograms/kg/min was given over 2 minutes and maternal and fetal cardiorespiratory parameters and fetal blood flow were measured 5.30 and 60 minutes later. Nicardipine reversed maternal hypertension and produced transient tachycardia. Fetuses responded initially with transient bradycardia and then developed hypercapnia and acidemia (p less than 0.03) by 60 minutes after nicardipine. Fetal placental blood flow decreased and vascular resistance increased by 5 minutes after nicardipine but returned toward control values after 30 minutes. Unexpectedly we observed the death of five fetuses by 65 minutes after nicardipine. We conclude that the administration of nicardipine in the hypertensive ewe results in significant alterations of fetal cardiorespiratory status and placental function that may lead to acidemia.     

Placental transfer of ritodrine hydrochloride in sheep

The purpose of this study was to examine the placental passage of ritodrine hydrochloride in relation to the drug's effects on the fetal circulation. Studies were carried out on nine nulliparous pregnant (120-140 days) ewes with chronically implanted cannulae for measurements of maternal and fetal arterial pressures and for blood sampling. One group of animals received sequential infusions of doses ranging from 0.1 to 30 micrograms/kg per min for 30 min (group 1). A second group was given a constant infusion of the drug at a dose of 3.0 micrograms/kg per min for 4 h (group 2). The peak concentrations of ritodrine in maternal and fetal blood were determined by radioimmunoassay. In group 1 they were 313.4 +/- 24.1 ng/ml (mean +/- S.E.) and 12.6 +/- 3.7 ng/ml at the finish of 30.0 micrograms/kg per min infusion for maternal and fetal blood, respectively. In group 2, maternal drug levels were 81.3 +/- 20.4 ng/ml after 30 min and 95.9 +/- 17.1 ng/ml after 4 h of the infusion. Fetal plasma concentrations increased slowly from trace levels at 30 min to 3.3 +/- 0.7 ng/ml at 4 h. Fetal blood pressure and heart rate did not show any significant changes during and after the infusion of ritodrine in both treatment groups. Our findings demonstrate the maternal administration of ritodrine produces no significant effects on the circulatory system of the fetal lamb because of the low transplacental passage of this drug.     

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.     

Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus

Cocaine is a potent vasoconstrictive agent that is currently the subject of widespread drug abuse. Because little is known of the physiologic responses to cocaine in pregnancy, the effects of intravenous cocaine on uterine blood flow and other maternal and fetal cardiovascular parameters were studied. Eight ewes in late pregnancy were equipped with electromagnetic flow probes around both uterine arteries and catheters were placed in the maternal and fetal inferior vena cavae and aortas. Bolus intravenous infusion of 0.5 and 1.0 mg/kg of maternal body weight achieved peak plasma cocaine levels similar to those observed in human subjects after abuse of the drug (mean level = 229 to 400 ng/ml, n = 8). After bolus infusion of 0.5 or 1.0 mg/kg of cocaine, mean maternal arterial pressure increased 32% and 37%, respectively (p less than 0.005). Fetal blood pressure rose 12.6% after a dosage of 0.5 mg/kg of cocaine. These cocaine infusions significantly decreased uterine blood flow by 36% and 42% for a duration of 15 minutes (p less than 0.005). Analysis of maternal catecholamine responses demonstrated a significant (210%) rise in plasma norepinephrine levels after cocaine infusion. These studies demonstrate that cocaine, when administered in doses that produce plasma levels observed in humans, significantly decreases uterine blood flow for a duration of greater than or equal to 15 minutes while inducing a hypertensive response in the pregnant ewe and fetus.     

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.     

Effect of maternal oxygen administration on fetal oxygenation during graded reduction of umbilical or uterine blood flow in fetal sheep.

OBJECTIVE: Effects of maternal oxygen administration on fetal blood gases and on oxygen delivery and consumption during reduced uterine and reduced umbilical blood flows were examined. STUDY DESIGN: In eight pregnant sheep (gestational age 133 +/- 4 days) flow transducers were applied to a uterine and the common umbilical artery. Graded reductions in uterine and umbilical blood flows were achieved by a hypogastric artery snare and a balloon cuff encircling the umbilical cord. Fetal femoral arterial and umbilical venous oxygen contents and flows were measured at varying flow reductions with the ewe breathing air or oxygen. RESULTS: During 75% reduction in umbilical blood flow maternal oxygen administration significantly increased fetal oxygen delivery (6.4 +/- 2.5 to 7.7 +/- 2.3 ml/min/kg) and oxygen consumption (4.3 +/- 1.2 to 5.0 +/- 0.8 ml/min/kg). With similar reduction of uterine flow oxygen administration increased oxygen delivery from 8.3 +/- 2.4 to 12.3 +/- 3.6 and oxygen consumption from 3.3 +/- 0.8 to 4.7 +/- 1.6 ml/min/kg. CONCLUSION: Maternal oxygen inhalation improves fetal oxygenation during umbilical but especially during uterine blood flow reduction.     

Concentrations of ritodrine hydrochloride in maternal and fetal serum and amniotic fluid following intravenous administration in late pregnancy

Seven healthy pregnant volunteers undergoing elective cesarean section at 39-40 weeks of gestation were studied for transplacental passage of ritodrine hydrochloride, which was administered by intravenous infusion at the rate of 72-149 micrograms/min for 161-335 min. The concentrations of ritodrine in the collected maternal and fetal blood and the amniotic fluid were radioimmunoassayed. The levels of ritodrine in maternal serum were between 22.5 and 51.0 ng/ml one hour after the initiation of infusion, 33.7-66.4 ng/ml after 2 h, 18.2-73.6 ng/ml after 4 h and 45.7-189.6 ng/ml at delivery, respectively. The umbilical blood and amniotic fluid concentrations of ritodrine at delivery were between 15.6 and 35.1 ng/ml in arterial blood, 12.5-29.6 ng/ml in venous blood and 10.0-49.1 ng/ml in amniotic fluid. The ratio of umbilical venous blood concentrations to maternal venous concentrations (CV/MV) ranged from 0.066 to 0.544 with the mean of 0.263 +/- 0.063 (M +/- S.E.). The results obtained substantiate the rapid and appreciable transfer of ritodrine to the fetus and amniotic fluid.     

Maternal and fetal effects of low-dosage bupivacaine paracervical block

Vasoconstriction of the uterine arteries, hypertonus of the uterus, and the direct toxic effects of a local anesthetic on the fetus or a combination of the above have been presented as etiological factors of fetal bradycardia following paracervical block. The reduce fetal side-effects a superficial and lowdosage technique of PCB have been advocated. We have studied the effects of 25 mg of bupivacaine PCB using the above technique on fetal heart rate pattern (FHR), fetal acid-base balance, uterine activity, placental blood flow and maternal and fetal plasma levels of bupivacaine in 38 patients. The analgesic effect of a single 25 mg of bupivacaine PCB was good in 76%, moderate in 12% and poor in 12% of the cases. No changes in maternal heart rate or in blood pressure were noted. Fetal bradycardia defined as a decrease of mean fetal heart rate of at least 20 bpm or an absolute rate less than 100 bpm and a duration greater than two minutes occurred in 12% of the cases. The mean amplitude of the baseline fetal heart rate variability decreased significantly after PCB and a silent pattern (an amplitude less than 5 bpm) was observed in 20% of the cases. The most frequent (27%) pathological finding in our study was the disappearance of FHR accelerations after PCB. Similarly early and late decelerations of FHR occurred more often after PCB than during the control period before the block. The fetal pH from scalp blood samples did not, on average, decrease after PCB, but did so in cases with fetal bradycardia. Intervillous blood flow as measured by the 133Xe washout method did not change when measured before and after PCB. In addition in three cases with fetal bradycardia the changes in the intervillous blood flow were minimal. No significant changes in the mean uterine tone, amplitude and frequency of contractions were observed after PCB. However, an obvious uterine hypertonus was observed after PCB was observed in three cases of fetal bradycardia but not in two other cases of bradycardia or in the 8 cases of silent FHR pattern. Mean maternal bupivacaine concentration 20 minutes after PCB was 0.14 +/- 0.06 microgram/ml and 0.07 +/- 0.04 microgram/ml at birth. Simultaneous fetal and umbilical venous and arterial concentrations were correspondingly 0.04 +/- 0.02 microgram/ml, 0.03 +/- 0.01 microgram/ml and 0.03 +/- 0.01 microgram/ml, and they were significantly lower than respective maternal concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Effect of continuous infusion of fenoterol on maternal pelvic and fetal umbilical blood flow in pregnant sheep

The results from studies on the reactions of the uterine vascular bed upon intravenous administrations of beta-adrenergic drugs to the ewe are not all identical. This can be partly explained by different reactions of the pelvic vasculature on beta-adrenergic receptor stimulation. In order to assess whether any differences in flow reactions existed between the vascular beds of two maternal pelvic vessels upon beta-adrenergic receptor stimulation, we studied the effect of continuous maternal intravenous infusion with fenoterol on the blood flow in the maternal internal iliac and the median uterine artery in seven chronically instrumented pregnant sheep between 104 and 142 days gestation. Furthermore, the effects on umbilical venous blood flow, fetal heart rate, blood pressure and acid-base balance were analyzed. Maternal and fetal blood flows were measured with electromagnetic flow transducers. Fenoterol was administered to the ewe via a continuous intravenous infusion in two sequential periods of 30 minutes duration in a dose of 2 respectively 4 micrograms per minute. The blood flow in the internal iliac artery showed an increase of 10.5% (p less than 0.05) at the end of the infusion period and was still but not significantly elevated during the postinfusion period. No significant changes in median uterine artery blood flow were found during the fenoterol infusion, although an incremental trend was present. Fenoterol infusion to the mother had no effect on umbilical venous blood flow. Fetal pH and PO2 did not change, while fetal PCO2 was reduced (p less than 0.005) at the end of the infusion and recovery period, probably as a result of the concomitant maternal hyperventilation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prolonged asphyxia on skin blood flow in fetal lambs

Objective: To determine the effect of a prolonged period of asphyxia on skin blood flow, a potential indicator of fetal cardiovascular responses to asphyxia, in the chronically catheterized fetal lamb. Methods: Eight chronically instrumented pregnant ewes were studied at 118 +/- 1 days' gestation. After a control period, fetal acid-base status was assessed and regional blood flows were determined with dye-labeled microspheres. Fetal asphyxia was then induced by partial umbilical cord occlusion, decreasing fetal arterial oxygen pressure to 15 torr while maintaining pH above 7.28. Fetal cardiovascular status was monitored continuously. Fetal acid base status was evaluated every 10-15 minutes during cord occlusion. Regional blood flow determinations were repeated after 90 minutes of stable asphyxia. Results are expressed as the mean +/- standard error. Student t test for paired data was used to compare hemodynamic, acid-base, and regional blood flow determinations before cord occlusion and after 90 minutes of asphyxia.Results: There was a significant increase in blood flow to the fetal scalp from a control value of 52 +/- 8 mL per minutes per 100 g to 175 +/- 30 mL per minute per 100 g at 90 minutes of asphyxia (P =.01). Similarly, there was an increase in blood flow to the skin overlying the fetal hindquarter from 39 +/- 12 mL per minute per 100 g during control to 153 +/- 47 mL per minute per 100 g at asphyxia (P =.038). Conclusion: In the chronically instrumented fetal lamb, a 90-minute period of asphyxia produced by partial cord occlusion resulted in a significant increase in blood flow to the fetal skin.     

Transplacental arteriovenous gradients for glucose, insulin, glucagon and placental lactogen during normoglycaemia in human pregnancy at term

The potential contributions of placental extraction and degradation to glucoregulatory hormone turnover in late pregnancy were assessed by measuring arteriovenous differences for glucose, insulin, glucagon and human placental lactogen (hPL) across the uterine and fetal circulation in ten pregnant women at the time of elective caesarean section. The observations were made during stable conditions of euglycaemia; values for maternal arterial glucose, insulin, glucagon and hPL were 78.8 +/- 5.0 mg/dl, 10.1 +/- 2.1 microU/ml, 72.0 +/- 8.5 pg/ml and 5.18 +/- 0.59 micrograms/ml, respectively. The glucose decrements observed consistently across the uterus and fetus indicated uptake by the placenta and fetus, and in the maternal circulation the arterial-uterine vein increment for hPL was 2.10 +/- 0.44 micrograms/ml. However, within the limits of analytical accuracy, no significant gradient could be demonstrated for insulin across the uterine (maternal) or umbilical (fetal) circulations. A small (8.5 per cent) but significant arteriovenous difference for glucagon was observed across the uterus but none was found on the fetal side of the placenta. The findings indicate that detectable gradients for insulin cannot be demonstrated under basal conditions of metabolism and at normal rates of placental blood flow. The results do not exclude the possibility of more significant extraction ratios under other physiological conditions or at higher concentrations of glucoregulatory hormones.     

Effect of continuous infusion of norepinephrine on maternal pelvic and fetal umbilical blood flow in pregnant sheep

The effect of continuous maternal intravenous infusion with norepinephrine on the blood flow in the maternal internal iliac and the median uterine artery was studied in ten chronically instrumented pregnant sheep between 104 and 146 days gestation. Furthermore the effects on umbilical venous blood flow, fetal heart rate and acid-base balance were analyzed. Maternal and fetal blood flows were measured with electromagnetic flow transducers. Norepinephrine was administered to the ewe via a continuous intravenous infusion in increasing sequential doses of 15 minutes duration from 4 to 40 micrograms per minute. Variations of often considerable magnitude associated with e. g. micturition, defecation and fear of the ewe occurred in the maternal pelvic blood flow during the steady state period. The blood flow in the maternal vessels substantially decreased immediately following the onset of the norepinephrine infusion but gradually returned towards the preinfusion level despite the continued drug infusion and except one no significant changes in blood flow were found at the end of each sequential infusion period. Umbilical venous blood flow did not change. No significant changes in fetal arterial blood pressure, heart rate and acid base balance were found. It is concluded that the decrease in maternal pelvic blood flow associated with continuous norepinephrine administration gradually abates with time, possibly by the involvement of local factors such as prostaglandin formation and/or by the phenomenon of down-regulation.     

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.     

Effects of ethanol on the circulation and acid-base balance of pregnant sheep

Nine infusions of 15 cc/kg/120 min of 9.5% ethanol were administered to 4 chronically catheterized ewes, at 109-135 days' gestation. Stabilization periods ranged from 6 to 28 days postoperatively. Maternal and fetal concentrations of ethanol were almost identical (r = 0.9925), with peak levels of 122 +/- 20 mg/100 ml (mean +/- 1 SE) and 121 +/- 19 mg/100 ml, respectively, at the end of infusion. Maternal pH decreased from 7.50 +/- 0.02 to 7.44 +/- 0.02 (P less than 0.005) at 120 minutes. Maternal glycemia increased from 76 +/- 14 mg/100 ml to 162 +/- 23 mg/100 ml (P less than 0.005) at 120 minutes. Maternal heart rate, blood pressure, PO2, O2 content, PCO2, and bicarbonate remained unchanged. Fetal PO2 increased during and following infusion from 18.9 +/- 0.9 mmHg to 22.0 +/- 1.0 mmHg (P less than 0.005) at 180 minutes. Fetal blood pressure increased from 51.3 +/- 3.1 mmHg to 53.7 +/- 3.3 mmHg (P less than 0.01) at 30 minutes. Fetal pH, PCO2, glucose, and lactate levels remained unchanged. The authors conclude that ethanol crosses the sheep placenta readily, causes maternal acidosis and hyperglycemia, and increases fetal PO2, blood pressure, and heart rate without any effects on fetal acid-base status.     

Thromboxane Receptor Blockade Causes Acidemia in the Ovine Fetus

The placenta produces the vasoactive eicosanoids thromboxane and prostacyclin. We hypothesized that fetal administration of SQ 29,548, a thromboxane receptor blocker, would lack direct cardiorespiratory effects in the ovine fetus. Continuous monitoring of maternal and fetal heart rates, blood pressures, and common umbilical artery blood flow was performed in six chronically catheterized pregnant ewes. Serial maternal and fetal arterial blood gases and serum lactates were obtained. After 120 minutes of infusion, a significant decrease in fetal mean arterial pressure and a significant increase in fetal heart rate was observed. A significant decrease in fetal arterial pH (7.41 ± 0.02 to 7.33 ± 0.02), PO₂ (26.8 ± 3.2 to 19.8 ± 3.4), HCO₃^? (27.2 ± 1.5 to 24.9 ± 2.0), and base excess (2.9 ± 1.6 to 0.2 ± 2.3) with a significant elevation in PCO₂ (45.4 ± 2.6 to 50.1 ± 3.3) occurred after 120 minutes of SQ 29,548 infusion. SQ 29,548 infusion caused a significant decrease in common umbilical artery flow, from 249.4 ± 19.4 ml ± min^?1 ·; kg^?1 fetal weight to 178.3 ± 17.9 ml · min^?1 · kg^?1 fetal weight at 120 minutes. Fetal blood lactate levels were significantly elevated from 22.0 ± 3.1 to 54.1 ± 3.8 mg/dL after 120 minutes of SQ 29,548 infusion. Prolonged infusion of SQ 29,548 results in umbilical-placental hypoperfusion and significant alterations in acid-base balance in the ovine fetus.     

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.     

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.     

Effect of nicotine upon uterine blood flow in the pregnant rhesus monkey

Acute effects of nicotine upon the uterine blood flow, blood pressure, maternal and fetal acid-base state, and oxygenation were determined in eight pregnant rhesus monkeys near term. Nicotine was infused intravenously to the mother in a dose of 100 microgram/kg per body weight/minute over 20 minutes. The flow rate was measured with the use of the electromagnetic flowmeter. Significant decrease in the uterine arterial blood flow rate, as much as 38% of the control value, was observed during the first 15 minutes of the infusion while aortic pressure increased by 14%. Acidosis and hypoxia resulted in the fetus. Considered together with our previously reported data, the present investigation appears to indicate that the adverse effects of nicotine to the fetus are due to the combined effects of the reduced uterine blood flow and the transmitted nicotine to the fetus.