Effects of maternal ethanol infusion on fetal cardiovascular and brain activity in lambs

Ethanol (1 gm/kg of maternal body weight administered over 1 hour) was infused intravenously into 11 chronically prepared pregnant ewes between 128 to 137 days' gestation. Fetal breathing movements were suppressed for 9 hours following ethanol administration, and both high- and low-voltage fetal electrocortical activity were suppressed for 3 hours and replaced by intermediate-voltage electrocortical activity. Fetal blood gases and pH were not altered. These data support the hypothesis that ethanol suppresses fetal breathing movements by a direct central mechanism rather than indirectly by alteration of electrocortical activity.     

Cerebral oxidative metabolism in fetal sheep with multiple-dose ethanol infusion

Cerebral oxidative metabolism and cotylendonary blood flow were measured in 10 unanesthetized fetal sheep (127 to 132 days' gestation) during a control period, after the first, third, and fourth infusions of four doses of 0.5 gm of ethanol per kilogram of maternal body weight infused into the ewe during 5 hours, and 24 hours after ethanol infusion. Preductal arterial and sagittal vein blood samples were analyzed for oxygen content, blood gases, pH, and ethanol. Cerebral and cotylendonary blood flow were measured with a radioactive microsphere technique. Fetal blood gases and pH changed little with the ethanol infusions, although PaO2 and oxygen content decreased 24 hours after ethanol infusion. Cotylendonary blood flow, which was decreased after the third and fourth ethanol infusions, did not account for these delayed hypoxemic changes. Similarly, cerebral oxidative metabolism was decreased when measured after each of the ethanol infusions, with no dose response or tolerance evident. This noted fall in fetal cerebral oxidative metabolism appears to be a direct depressant effect that was maximal at rather low fetal ethanol levels, which, if prolonged, might well affect cerebral growth and development. Recovery of cerebral metabolic function appeared complete by 24 hours. However, relative fetal hypoxemia was evident at this time, the mechanism of which remains to be determined.     

Effects of cholic acid infusion in fetal lambs

The effects of prolonged intravenous infusions of cholic acid into fetal lambs are described in this study. The ewes (n = 10, 11 fetuses) were operated on at 114 days of gestation (term = 150 days) by placing plastic catheters in maternal and fetal vessels and in the amniotic cavity. Gestational ages were confirmed after delivery by radiographic examination of the ossification centers of the fetal legs. Infusions of cholic acid (1.6 mumoles/min-1) started 8 to 10 days after surgery in 5 fetuses (including one twin). The remaining 6 fetuses (also including one twin) were infused with 5% dextrose in water. Total plasma bile acids at the beginning of the experiment were similar in both groups (23.8 +/- 6.6 vs. 24.3 +/- 5.7 microM). No significant changes in fetal heart rate, blood pressure, blood gases or pH were detected during the infusion. Meconium-stained amniotic fluid was observed during the third day of infusion in all the fetuses infused with cholic acid and in one control fetus. Fetuses infused with cholic acid were delivered alive 19-26 days before term. The concentration of plasma bile acids in the experimental group at delivery was 829 +/- 305 microM, i.e. significantly higher than that of the control group (24.4 +/- 5.7 microM). Control fetuses (except one twin) were delivered at term. We concluded that cholic acid, even at the high dose infused, is neither lethal nor severely harmful for the fetus. Meconium passage of the fetuses infused with cholic acid, in our experiment, appeared to be related to the stimulatory effect of cholic acid on fetal colonic motility rather than to fetal hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic and cardiovascular changes during prolonged ritodrine infusion in fetal lambs

Prophylaxis of threatened premature labor with ritodrine may lead to prolonged fetal exposure to the drug. To investigate the direct consequences of this, 11 fetal lambs were given ritodrine hydrochloride for periods of 2-4 days by continuous intravenous infusion at 5 or 10 micrograms/minute (1-3 micrograms/minute/kg estimated fetal weight). These dosages had no measurable effects on the ewes. In the fetus, measurements confirmed and extended the results of earlier short-term experiments, but differences from the effects of long-term maternal ritodrine infusion imply little placental transfer of the drug in sheep. Ritodrine had little or no effect on mean arterial pressure, blood pH, pCO2, plasma alpha-amino acid nitrogen, or growth hormone, but resulted in marked hypoxemia, tachycardia, hyperlactacidemia, hyperglycemia, and hyperinsulinemia during the first 24-48 hours of infusion. Despite continued ritodrine infusion, heart rate and the metabolic parameters returned toward normal within 72 hours. Hypoxemia persisted longer, but tended to lessen after 2 days of infusion. The results indicate that tachyphylaxis to ritodrine develops in the fetal lamb during prolonged administration, but that when fetal well-being is already compromised, ritodrine's effects on oxygenation and lactacidemia could jeopardize fetal survival.     

Acute effects of maternal ethanol infusion on fetal cardiac performance

In adult animals and man, both acute and chronic ethanol intake is associated with depression of myocardial performance. Accordingly, the cardiac effects of maternal ethanol infusions, in a manner comparable to common obstetric practice for inhibition of premature labor, were evaluated in six chronically instrumented fetal sheep. Fetal and ewe arterial Po₂, Pco₂, and pH values remained within normal limits with infusion rates of 15 c.c. per kilogram of 10 per cent ethanol over two hours (blood ethanol = 110 mg. per cent) and 15 c.c. per kilogram over one hour (blood ethanol = 210 mg. per cent). Fetal instrument evaluation (for 14 to 30 days after operation) provided data concerning pressures and cardiac dimensions which allowed analysis of left ventricular performance. Ethanol produced a significant depression of the extent (p < 0.01) and velocity (p < 0.001) of left ventricular myocardial fiber shortening as well as in the mean rate of left ventricular circumferential fiber shortening (p < 0.01). These indices of cardiac contractility were depressed in the absence of changes in end diastolic diameter, left atrial pressure, and systemic arterial pressure. Thus, the practice of inhibition of premature labor with ethanol might contribute to depressed myocardial performance in the neonatal period.     

Decreased urine production in the near-term fetal lamb after maternal ethanol infusion

Intravenous infusion of 1 gm ethanol/kg maternal body weight over 1 hour to three conscious catheterized near-term pregnant ewes decreased fetal urine production for 3 hours (overall decrease of 54% from control). This effect in the near-term fetus is opposite to the ethanol-induced diuresis that occurs in adults.     

Effects of maternal oxygen administration on fetal oxygenation during reductions in umbilical blood flow in fetal lambs

In 11 chronically catheterized fetal lambs (123 +/- 6, mean +/- SD, days of gestation; term = 147 days), we measured fetal oxygen delivery and oxygen consumption before and during reductions in umbilical blood flow (Qumb). Qumb was reduced by inflation of a balloon occluder located just proximal to the origin of the common umbilical artery. Measurements were made while the unanesthetized maternal sheep received either room air or 100% oxygen to breathe. In oxygen-treated fetuses, oxygen concentrations in umbilical venous blood (Cuvo2) and arterial blood (Cao2) were increased over a wide range of Qumb when compared with those of room air-treated fetuses. Because of these responses, fetal oxygen delivery (Do2 = Qumb X Cuvo2) and oxygen consumption [Vo2 = Qumb(Cuvo2-Cao2)] were greater in oxygen-treated fetuses than in room air-treated fetuses during episodes of reduced Qumb. In oxygen-treated fetuses, Vo2 decreased from normal levels only when Qumb was less than or equal to 75 ml/min/kg of fetus, whereas in room air-treated fetuses Vo2 decreased at Qumb less than or equal to 150 ml/min/kg. Our data indicate that oxygen administration to the pregnant sheep increases oxygen delivery to the fetus during times of reduced umbilical perfusion and that this supplemental oxygen supply provides an oxygen reserve with which the fetus can maintain oxidative metabolism. These data may be relevant to those clinical conditions, such as umbilical cord compression in labor, that are associated with reductions in umbilical blood flow.     

Effects of chronic hyperglycemia on electrocortical activity states in unanesthetized fetal lambs

Electrocortical activity (ECoG), tracheal pressure and nuchal muscle activity were recorded in utero in 8 chronically hyperglycemic and 10 control unanesthetized fetal lambs to investigate the effects of chronic hyperglycemia on fetal electrocortical activity states. The chronically hyperglycemic state, induced by alloxan administered to the ewes, existed for at least 40 days prior to the experiments. The mean duration of episodes of high voltage (HV) ECoG was significantly increased in the hyperglycemic group (mean +/- SD: 21.8 +/- 9.2 min) compared with the control group (14.8 +/- 3.3 min), but the incidence of low voltage (LV) ECoG was not different between the groups. ECoG power spectra were not different between the groups. During LV ECoG, the proportions of time with neck movements were significantly less in the hyperglycemic than in the control group. No difference in percentages of time with long neck muscle activity was seen during the HV state in both groups. The incidence of breathing movements was equal in both groups, during HV as well as LV ECoG. No differences in breathing interval were observed.     

Effect of short-term maternal exercise on maternal and fetal cardiovascular dynamics

Summary. Maternal and fetal cardiovascular dynamics were studied immediately after moderate short-term maternal exercise in 28 healthy nulliparous subjects at between 34 and 38 weeks gestation who were randomly assigned to an exercise group ( n = 14) or a control group ( n = 14). At the end of the study, data from 11 exercise and 12 control subjects were available for analysis. A significant rise in maternal heart rate and systolic and diastolic blood pressure during exercise was observed. Mean blood flow velocity in the fetal descending aorta as measured by pulsed Doppler ultrasound and fetal heart rate did not show any significant changes. These data indicate that there are no cardiovascular signs of fetal stress immediately after moderate short-term maternal exercise.     

Effect of short-term maternal exercise on maternal and fetal cardiovascular dynamics

Maternal and fetal cardiovascular dynamics were studied immediately after moderate short-term maternal exercise in 28 healthy nulliparous subjects at between 34 and 38 weeks gestation who were randomly assigned to an exercise group (n = 14) or a control group (n = 14). At the end of the study, data from 11 exercise and 12 control subjects were available for analysis. A significant rise in maternal heart rate and systolic and diastolic blood pressure during exercise was observed. Mean blood flow velocity in the fetal descending aorta as measured by pulsed Doppler ultrasound and fetal heart rate did not show any significant changes. These data indicate that there are no cardiovascular signs of fetal stress immediately after moderate short-term maternal exercise.     

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.     

Effect of fetal hypercapnia on maternal and fetal cardiovascular and respiratory function

After direct infusion of a carbonic anhydrase inhibitor to the fetus the fetal PCO2 increased to 70-80 mm Hg. Under the conditions of our sheep preparation no changes were seen in uterine or umbilical blood flows.     

The effects of xylazine on uterine activity, fetal and maternal oxygenation, cardiovascular function, and fetal breathing

Various pharmacologic agents used in the experimental study of physiologic processes may have pronounced effects on the systems under study. We have studied the effects of xylazine (Rompun) on myometrial activity, fetal and maternal pH, blood gases, heart rate, and fetal breathing movements in chronically catheterized fetal sheep. Xylazine is widely used as a premedication for various forms of animal operations, including the instrumentation of the chronically catheterized fetal sheep preparation. Animals were studied on postoperative day 5. Xylazine had pronounced effects on maternal PaO2 and heart rate that lasted for at least 3 hours. Fetal heart rate and PaO2 returned to preinjection levels within 60 minutes. Myometrial activity doubled in the first 60 minutes after administration of xylazine and did not return to preinjection levels for 3 hours. Fetal diaphragmatic electromyographic activity was almost completely absent in the first and second hours, with a return to normal within 4 hours. These changes were absent in the saline solution-injected control animals. The observed changes in uterine activity and fetal breathing may have been direct effects of xylazine itself or the result of increased uterine activity. The different duration of changes in the ewe and fetus suggests a compensatory mechanism at the uteroplacental level or in the fetoplacental unit.     

Oxygen consumption in fetal lambs after maternal administration of sodium pentobarbital

To determine whether anesthesia lowers fetal oxygen consumption, sodium pentobarbital (10 mg/kg) was given intravenously to seven chronically instrumented pregnant ewes (123 to 144 days' gestation). Oxygen consumption fell by 23% in association with a rise in fetal vascular PO2. Fetal breathing movements were abolished for 50.5 minutes, while the number of fetal heart rate accelerations fell by 80% in the first 30 minutes after pentobarbital injection. It is concluded that anesthesia reduces fetal oxygen consumption, probably by abolishing skeletal muscle activity, and perhaps also by reducing cerebral metabolic rate.     

Effects of fetal breathing movements on umbilical venous blood flow in fetal lambs

The effects of fetal breathing movements on the blood flow pattern in the common umbilical vein were studied in six chronically instrumented fetal lambs between 106 and 143 days gestation. Umbilical venous blood flow was measured with an electromagnetic flow transducer around the intra-abdominal common umbilical vein. Fetal breathing movements were recorded by means of an intratracheal catheter. During rapid irregular breathing movements instantaneous umbilical venous blood flow showed undulations with the frequency of the breathing movements. An inspiratory movement, characterized by a fall in tracheal pressure (mean +/- S.D. = 5.3 +/- 1.7 mmHg) was accompanied by a decrease in instantaneous umbilical venous blood flow (mean +/- S.D. = 10.5 +/- 2.8%). This decrease in umbilical blood flow during inspiration was accompanied by an increase in intra-abdominal pressure. A much greater decrease (mean +/- S.D. = 40.6 +/- 18.4%) in instantaneous umbilical venous blood flow occurred during deep inspiratory efforts (mean pressure drop +/- S.D. = 15.5 +/- 4.3 mmHg), accompanied by marked increases in intra-abdominal pressure. Isolated expiratory efforts resulted in an increase in both tracheal (mean +/- S.D. = 6.3 +/- 2.6 mmHg) and intra-abdominal pressure, while umbilical venous blood flow decreased (mean +/- S.D. = 33.5 +/- 21.3%). These observations show the great influence of fetal respiratory movements on the blood flow pattern in the common umbilical vein. The changes in instantaneous umbilical venous blood flow are possibly brought about by changes in intra-abdominal pressure.     

Intrapartum maternal glucose infusion and fetal acid-base status.

OBJECTIVE: To compare the effects of an intrapartum infusion of a lactated Ringer solution or a glucose-boosted saline solution on the acid-base status of umbilical arterial blood. METHOD: In a prospective clinical trial 178 women in labor were randomized to receive intravenously either a lactated Ringer solution or a saline solution boosted with 5% glucose. Umbilical arterial blood was then assessed for acid-base status. RESULTS: There were significant differences between the lactated Ringer group and the glucose group in umbilical artery pH values (7.25+/-0.07 vs. 7.28+/-0.06; P=0.008), pCO2 values (44.8+/-5.6 mm Hg vs. 41.6+/-4.1 mm Hg; P=0.001), and base excess (-7.3+/-2.1 mEq/L vs. -6.6+/-1.8 mEq/L; P=0.02). CONCLUSION: Intrapartum intravenous fluid containing a 5% glucose solution reduces umbilical cord acidemia and hypercarbia.     

Effects of central angiotensin II receptor antagonism on fetal swallowing and cardiovascular activity

OBJECTIVE: Fetal plasma angiotensin II levels are 10 times the levels found in adults. Despite these high levels, central injection of angiotensin II may stimulate fetal swallowing and increase fetal arterial blood pressure. We postulated that the high rate of spontaneous fetal swallowing and normal fetal pressor regulation may be dependent, in part, on central angiotensin II. In view of the potential dipsogenic role of both type 1 and type 2 angiotensin II receptors, we examined the central effect of the nonselective angiotensin II receptor antagonist saralasin on fetal swallowing and cardiovascular responses. STUDY DESIGN: Six time-dated pregnant ewes and fetuses were chronically prepared with fetal vascular and intracerebroventricular catheters, electrocorticograms, and esophageal electromyogram electrodes and studied at 130 +/- 1 days' gestation. After an initial 2-hour baseline period (0 to 2 hours), saralasin (1 mL, 64 microg) was injected intracerebroventricularly (2 to 4 hours). After 4 hours the dose of saralasin was repeated together with angiotensin II (1 mL, 6.4 microg), and the fetuses were monitored for a final 2 hours. Four fetuses also underwent an identical control study (on an alternate day) in which saralasin was replaced with artificial cerebrospinal fluid. RESULTS: Blockade of central angiotensin II receptors by intracerebroventricular saralasin significantly reduced mean (+/- SEM) spontaneous fetal swallowing (1.3 +/- 0.1 to 0.4 +/- 0.1 swallows per minute; P <.001) but did not alter fetal mean blood pressure (50 +/- 5 versus 56 +/- 5 mm Hg). Intracerebroventricular angiotensin II, in the presence of saralasin, did not affect swallowing (0.6 +/- 0.1 swallows per minute) or fetal blood pressure. In the control study, intracerebroventricular artificial cerebrospinal fluid did not change fetal swallowing (0.9 +/- 0.1 versus 1.0 +/- 0.1 swallows per minute), whereas intracerebroventricular angiotensin II significantly increased swallowing activity (1.0 +/- 0.1 versus 2.0 +/- 0.1 swallows per minute; P <.001) and fetal blood pressure (51 +/- 2 to 59 +/- 3 mm Hg; P =.003). CONCLUSIONS: Tonic activity of central angiotensin II receptor stimulation contributed to the high rate of basal ovine fetal swallowing but not fetal basal blood pressure. Angiotensin II-mediated fetal dipsogenic and pressor responses are a result of specific angiotensin II receptor binding in central brain regions. These results indicate that fetal exposure to angiotensin II antagonists or angiotensin-converting enzyme inhibitors may have adverse effects on fetal and amniotic fluid homeostasis.