Fetal Arterial Blood Pressure Research Articles

The adrenocorticotropic hormone and arginine vasopressin responses to hypercapnia in fetal and maternal sheep.

Previous studies have demonstrated that fetal adrenocorticotropic hormone (ACTH) and arginine vasopressin (AVP) are increased during periods of acidemia produced by infusion of acid intravenously or by acidemia secondary to hypovolemia. The purpose of this study was to quantify ACTH and AVP responses to hypercapnic acidemia and to test the role of the peripheral chemoreceptors in the control of these responses. Chronically catheterized fetal sheep were subjected to carotid sinus denervation and bilateral vagotomy or were studied intact. At least 5 days after surgery, fetuses were exposed to a 60-min period of normocapnia or hypercapnia, delivered via a polyethylene bag containing 5-8% CO2 in 21% O2 fitted over the head of the pregnant ewe. Hypercapnia significantly increased fetal arterial PCO2 to 55.2 +/- 1.8 and 55.9 +/- 2.2 mmHg and decreased arterial pH to 7.257 +/- 0.011 and 7.281 +/- 0.010 in intact and denervated fetuses, respectively. Fetal mean arterial blood pressure was decreased slightly in the denervated fetuses during hypercapnia. Fetal plasma AVP was increased in both groups equally, and plasma ACTH and cortisol were increased in the denervated fetuses only. Fetal heart rate was increased significantly in intact but not denervated fetuses. We conclude that respiratory acidemia is a mild stimulus to AVP secretion and that this response is not attenuated by peripheral chemodenervation.

Effects of repeated administration of cocaine to the fetal sheep in the last days of pregnancy

There are no reports on the direct effects of repeated cocaine administration to the fetus in late pregnancy. The aim of our study was therefore to examine the effects of repeated fetal exposure to cocaine on fetal development. Ten fetal sheep were instrumented at 123 +/- 1 days' gestation. Five fetuses received a single daily intravenous injection of cocaine (2 mg/kg) commencing at 130 to 131 days of gestation until delivery at 132 to 144 days of gestation; those fetuses were compared with fetuses that did not receive cocaine (n = 5). Basal fetal arterial blood gas values, blood pressure, heart rate, and nuchal and diaphragmatic activities did not change in the days preceding labor. Fetal arterial PO2 fell after cocaine administration, but this was significant only on the first day. Cocaine induced consistent significant alterations in fetal pH and PCO2, blood pressure, and heart rate. During labor cocaine stimulated diaphragmatic and nuchal muscle activity when compared with the other days. There was no increase in diaphragmatic and nuchal muscle activity in the controls. Our studies indicate that in fetal sheep the cardiovascular and blood gas response to cocaine in late pregnancy is not altered by repeated exposure to cocaine and that cocaine stimulates fetal breathing during labor.

Fetal hemodynamic response to maternal intravenous nicotine administration

OBJECTIVES: Our study was designed to test the hypothesis that maternally administered nicotine has significant effects on fetal hemodynamics and umbilical systolic/diastolic ratios.STUDY DESIGN: Nine pregnant ewes received maternal intravenous infusions of 10, 20, and 30 µg/kg/min of nicotine. Maternal and fetal blood pressure, heart rate, and uterine and umbilical blood flow were recorded.RESULTS: Maternal intravenous administration of nicotine (10, 20, and 30 µg/kg/min of maternal body weight) produced significant (p < 0.05) increases in fetal blood pressure (2%, 11%, and 25%, respectively), decreases in fetal heart rate (0%, 8%, and 12%), and decreases in umbilical blood flow (0%, 0%, and 19%). Umbilical systolic/diastolic ratios increased slightly at the 30 µg/kg/min dose of nicotine, but these changes did not reach significance. Maternal blood pressure increased (10%, 25%, and 53%), and uterine vascular resistance increased (5%, 64%, and 344%) significantly (p < 0.05); uterine blood flow increased at the 10 µg/kg/min dose ( + 5%) and decreased by 23% and 42% at the highest two doses of nicotine.CONCLUSION: Maternal nicotine administration in late-term pregnant sheep produced significant increases in fetal arterial blood pressure and umbilical vascular resistance, decreased fetal heart rate, and umbilical blood flow but did not significantly alter systolic/diastolic ratios. (AM J OBSTET GYNECOL 1992;167:1624-31.)

Concentration thresholds for fetal swallowing and vasopressin secretion.

In adults, plasma osmolality thresholds for hypernatremia-induced arginine vasopressin (AVP) secretion are similar or less than thresholds for stimulation of thirst. In the fetus, the thresholds for swallowing stimulation and AVP secretion have not been defined. Fetal swallowing and AVP secretory responses to hypertonic NaCl and urea were determined in six fetuses (130 +/- 1 1 days) chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyograms (EMG), an esophageal flow probe, and vascular catheters. Fetuses received intracarotid injections (0.15 ml/kg) of increasing concentrations of NaCl (0.15, 0.30, 0.45, 0.60, 0.75, and 0.90 M), administered at 2-min intervals. A swallow was defined as a coordinated time-sequence of fetal thyrohyoid, nuchal esophagus, and thoracic esophagus EMG activity. The threshold saline concentration for swallowing was defined as the minimum NaCl dose eliciting swallow responses (within 20 s) after four of five injections at each dose. During a 2-h control period swallowing averaged 25.0 +/- 10.1 ml/h and 39.4 +/- 14.6 swallows/h. The mean NaCl threshold concentration for swallowing stimulation was 0.56 +/- 0.06 M. Fetal plasma AVP (2.6 +/- 0.9 pg/ml) increased significantly at the maximum subthreshold (7.6 +/- 4.0 pg/ml) and the threshold NaCl concentration (8.2 +/- 4.0 pg/ml) that stimulated swallowing. On a subsequent day, equiosmolar urea injections increased plasma AVP (from 2.2 +/- 0.7 to 7.6 +/- 2.6 pg/ml) but had no effect on swallowing activity. Fetal mean arterial blood pressure increased after injections of threshold saline and urea concentrations. Fetal arterial blood osmolality and sodium concentration did not change during any study.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal and maternal plasma atrial natriuretic factor responses to angiotensin II infusion

Plasma atrial natriuretic factor and angiotensin II have opposing actions in the regulation of body fluid homeostasis and systemic blood pressure. Angiotensin II infusions stimulate atrial natriuretic factor release in some, but not all, studies in adult mammals. To examine the response during the perinatal period, graded intravenous angiotensin II infusions were administered to four chronically instrumented pregnant ewes and fetuses (132 ± 1 days of gestation). Fetuses received successive 20-minute intravenous angiotensin II infusions at 25, 50, and 100 ng/kg/min. After a 90-minute recovery, maternal ewes received successive 20-minute angiotensin II infusions (5, 10, and 25 ng/kg/min). During the fetal infusions, mean (± SEM) fetal arterial blood pressure (47 ± 2 to 61 ± 2 mm Hg, p < 0.05) and heart rate (155 ± 16 to 196 ± 36 beats/min, p < 0.05) increased, although there was no change in maternal measured parameters. In response to the maternal infusion, maternal mean arterial blood pressure increased (92 ± 7 to 110 ± 8 mm Hg, p < 0.05) and maternal heart rate decreased (136 ± 4 to 125 ± 2 beats/min, p < 0.05) without change in fetal parameters. Fetal plasma atrial natriuretic factor levels (210 ± 27 to 664 ± 250 pg/ml, p < 0.05) significantly increased during the fetal angiotensin II infusions in spite of no change in maternal plasma atrial natriuretic factor (85 ± 21 to 124 ± 22 pg/ml) during the maternal angiotensin II infusions. These findings indicate that similar increases in systemic blood pressure in response to angiotensin II infusions stimulate increased fetal, but not maternal, plasma atrial natriuretic factor. (AM J OBSTET GYNECOL 1991;165:1635-41.)

Intraruminal rehydration of ovine fetuses

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.

Regional brain blood flow and oxygen supply in guinea pig fetuses near term

To examine brain blood flow and oxygen supply to 14 brain regions in fetal guinea pigs near term, 6 fetuses were catheterized under general anaesthesia of the dam between days 61 and 63 of pregnancy. Fetal arterial blood pressure was measured and a blood sample was taken from the right axillary artery to determine fetal blood gases and acid-base balance. Isotope-labelled microspheres were then injected in a lateral saphenous vein and a reference blood sample was taken from the right axillary artery according to Carter and Gu [1]. Preductal arterial haemoglobin oxygen saturation ranged from 16–33% (26.7 ± 6.3 mean ± SD) and pH from 7.08–7.30 (7.20 ± 0.09); oxygen content varied between 3.0–6.7 ml/dl. Blood flow to the whole brain was 105–258 ml/min per 100 g (167 ± 58), oxygen supply to the brain was 6.6–10.7 ml O 2/min per 100 g (8.0 ± 1.6). Both regional brain blood flow and oxygen supply were significantly different in the various brain parts. They were highest in the spinal medulla and in other parts of the brain stem and lowest in the cerebrum. Brain blood flow increased significantly with increasing pCO 2 and systolic blood pressure and with decreasing haemoglobin oxygen saturation, pH, base excess, and arterial oxygen content. On the other hand, except for the mid portion of the spinal medulla, there were no correlations between blood gas and acid-base balance variables and the oxygen supply to the whole brain or to various regions of the brain. We conclude that both the amount and the distribution of brain blood flow in fetal guinea pigs near term agree well with those of other animal species. Furthermore, there is a close relationship between brain blood flow and fetal oxygenation.

Fetal swallowing: response to graded maternal hypoxemia

A computer-based system, incorporating electromyography (EMG) and esophageal fluid flow measurement, was used to determine fetal breathing and swallowing responses to graded maternal hypoxemia. Five chronically prepared ewes with singleton fetuses at a gestational age of 130 +/- 2 (SE) days were subjected to successive 30-min periods of mild and moderate hypoxemia (inspired O2 fraction = 0.16 and 0.13, respectively). Mild and moderate maternal hypoxemia evoked significant reductions in fetal arterial PO2 (21 +/- 1 to 17 +/- 1 and 13 +/- 1 Torr, respectively), while fetal arterial pH, hematocrit, plasma osmolality, heart rate, and mean blood pressure did not change. Moderate hypoxemia was associated with significant increases in fetal plasma arginine vasopressin and renin activity and significant reductions from basal values in percent time breathing (53 +/- 4 to 25 +/- 12%), percent time swallowing (11.5 +/- 3.1 to 1.3 +/- 0.7%), and volume swallowed (21.3 +/- 2.1 to 4.8 +/- 2.7 ml/30 min). Fetal swallowing activity was better correlated with arterial PO2 (r = 0.8) than breathing activity (r = 0.45). We conclude that fetal swallowing is suppressed during mild and moderate hypoxemia. It is suggested that several sites and/or mechanisms may account for the hypoxemic inhibition of fetal activities.

Fetal hypertension induced by norepinepbrine infusion and umbilical artery flow velocity waveforms in fetal sheep

This study was designed to examine the effects of fetal hypertension on the umbilical artery pulsatility index. Fetal arterial blood pressure and umbilical venous pressure were measured in eight sheep, 3 to 5 days after surgery. Umbilical blood flow was measured with an electromagnetic flowmeter around the common umbilical vein. Umbilical artery flow velocity waveforms were obtained either by an indwelling 5 MHz pulsed Doppler device (n = 4) or transcutaneously by a 4 MHz continuous-wave Doppler device (n = 4). Fetal blood pressure was raised by intravenous infusion of norepinephrine 10 micrograms/min during 5 minutes. Norepinephrine infusion resulted in elevated arterial and umbilical venous pressures, accompanied by a bradycardia during the first 3 minutes. Umbilical blood flow, calculated placental vascular resistance, and umbilical artery pulsatility index did not change. After atropine administration, the norepinephrine-induced elevated arterial and umbilical venous pressures were accompanied by tachycardia, increased umbilical blood flow, and no change in placental vascular resistance and umbilical artery pulsatility index. It is concluded that fetal arterial hypertension provoked by norepinephrine infusion has no effect on placental vascular resistance, umbilical blood flow, and umbilical artery pulsatility index.

Effect of R(-)2,5-dimethoxy-4-methylamphetamine on uterine and umbilical blood flow in conscious pregnant sheep

Pregnant sheep and their fetuses were instrumented between 110 to 120 days of gestation (term, 145 days) for monitoring maternal and fetal arterial blood pressure, heart rate and blood flow in the maternal uterine and fetal intra-abdominal umbilical arteries. The administration of 2,5-dimethoxy-4-methylamphetamine (DOM, a 5-HT 2 agonist) i.v. to the ewe in doses ranging from 1 to 20 μg/kg of ewe body weight produced dose-dependent decreases in the blood flow of the uterine and umbilical arteries. This was accompanied by an increase in the arterial blood pressure of the mother and fetus and a decrease in the fetal heart rate. DOM significantly increased the vascular resistance to blood flow in the uterine and umbilical arteries. The maximal increase in the vascular resistance of the uterine and umbilical arteries was 19.6- and 2.6-fold, respectively. Ketanserin, a 5-HT 2 antagonist (1 mg/kg), administrated 30 min prior to DOM significantly inhibited the reduction in blood flow in the uterine and umbilical arteries to DOM and blocked the increased vascular resistance in these vessels. The inhibitory effects of ketanserin on the responses to DOM in the uterine and umbilical arteries were surmountable. Our results indicate that DOM is a potent constrictor of the uterine and umbilical vasculature which may lead to fetal distress as evidenced by a decrease in fetal heart rate and arterial blood PO 2. 5-HT 2 receptor stimulation by DOM may be involved in these effects since they were blocked by ketanserin.

Effect of Bilateral Splanchnic Nerve Section on Adrenal Function in the Ovine Fetus*

The effect of bilateral splanchnic nerve (SPLX) section in fetal sheep [116-121 days gestational age (dGA)] on subsequent adrenocortical function was investigated. Fetal cortisol release was stimulated by 1) ACTH-(1-24) administration (100 ng/min for 15 min) at 126-129 and at 132-135 dGA, and 2) nitroprusside-induced hypotension (50% reduction in fetal arterial blood pressure for 10 min) at 129-132 and 136-139 dGA. No differences were observed between SPLX and control fetuses (CONT) in basal arterial plasma concentrations of cortisol from 126-141 dGA. A significant effect of fetal age on basal cortisol was observed in both SPLX and CONT fetuses from 126-141 dGA. A significant (P less than or equal to 0.05) increase in fetal arterial concentrations of cortisol was achieved by ACTH-(1-24) infusion in SPLX and CONT and did not differ between groups at either 126-129 or 132-135 dGA. Hypotension induced a significant increase in fetal plasma cortisol concentrations in SPLX and CONT fetuses (P less than or equal to 0.05). SPLX fetuses secreted significantly less cortisol in response to hypotension than CONT fetuses at both 129-132 and 136-139 dGA (P less than 0.05). Fetal arterial plasma concentrations of immunoreactive ACTH in response to hypotension were not different between CONT and SPLX fetuses. We estimated the half-life of endogenous fetal plasma cortisol after both hypotension and infusion of ACTH-(1-24). There were no differences between either method of inducing cortisol release on the endogenous cortisol half-life, nor were any differences in cortisol half-life observed between SPLX and CONT. At 136-139 dGA the adrenomedullary response to hypotension was abolished in SPLX, confirming completeness of denervation. In conclusion, the splanchnic nerves do not appear to be involved in the normal increase in basal fetal plasma cortisol observed in late gestation in fetal sheep. However, splanchnic nerve modulation of secretion of cortisol in response to stress may be involved in the increased fetal adrenal sensitivity to stress observed late in gestation.

Differential responses of uterine and umbilical vasculatures to angiotensin II and norepinephrine

Although the uterine vascular responses to endogenous vasoactive substances have been extensively investigated in pregnant sheep, the fetal umbilical responses to angiotensin II (ANG II) and norepinephrine (NE) have not been well characterized. Twenty-five pregnant ewes between 105 and 115 days of gestation were anesthetized and instrumented for hemodynamic measurements, systemic fetal and maternal intravenous infusions, and local maternal uterine arterial infusions of ANG II and NE. Fetal and maternal arterial pressure and heart rate, maternal uterine blood flow (total of left and right middle uterine arteries), and fetoplacental blood flow (common umbilical artery) were measured during continuous infusions of ANG II or NE. Fetal infusions of ANG II (0.03-1.0 micrograms.min-1.kg estimated fetal body wt-1) increased fetal arterial blood pressure by as much as 44% over base-line values, decreased umbilical blood flow by as much as 63%, and increased umbilical vascular resistance by up to 345%. Fetal infusions of NE (0.1-3 micrograms.min-1.kg-1) increased fetal arterial pressure 42% and increased umbilical vascular resistance by up to 38% but did not significantly alter fetoplacental blood flow. No significant maternal changes were observed during fetal infusions. Maternal infusion of ANG II increased maternal arterial pressure by as much as 59% and significantly increased uterine vascular resistance at the two highest doses but significantly decreased uterine blood flow only at the highest dose (17%; P less than 0.05). Maternal infusions of NE increased arterial pressure by as much as 113%, decreased uterine blood flow by as much as 76%, and increased uterine vascular resistance 3- to 10-fold over the base-line value.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal Uptake of Intraamniotic Digoxin in Sheep

To explore the possibility that intraamniotic administration of digoxin is an effective treatment regimen for fetal tachyarrhythmia, we injected digoxin into the amniotic fluid cavity of pregnant sheep and examined the time course of digoxin distribution to the fetal and maternal plasma compartments. Animals were studied in two groups according to digoxin dosage: 0.7-1.8 nmol/kg fetal body wt in the high-dose group (n = 6) and 0.1-0.6 nmol/kg fetal body wt in the low-dose group (n = 14). Within 1 h, plasma digoxin concentrations in the high-dose and low-dose groups were 18.2 +/- 15.0 nmol/L and 2.7 +/- 0.8 nmol/L, respectively (values are expressed as mean +/- SD). At 6 h digoxin concentrations were 13.8 +/- 7.0 and 3.1 +/- 0.9 nmol/L, and at 24 h they were 2.3 nmol/L (n = 1) and 1.8 +/- 1.2 nmol/L, respectively. Peak maternal digoxin levels were about one-tenth fetal values in the high-dose group and undetectable in the low-dose group. Fetal digoxin concentrations were significantly greater in the descending aorta than in the umbilical vein (p less than 0.02). Fetal arterial blood pressure and heart rate were not significantly different from control at any time after digoxin administration. These results demonstrate that digoxin is rapidly taken up into the fetal circulation from the maternal amniotic cavity. The exact mechanism whereby this occurs is unknown, but transplacental transfer from the maternal circulation is not involved. Our findings suggest that intraamniotic administration of digoxin may be an alternative treatment for fetal tachyarrhythmias when direct administration of antiarrhythmic agents is ineffective or produces maternal toxicity.

Fetal swallowing: response to systemic hypotension

The fetal swallowing and endocrine responses to systemic hypotension were studied in five chronically instrumented ovine fetuses (125 +/- 2 days). Fetuses were prepared with bipolar electrodes inserted in the thyrohyoid muscle, nuchal esophagus, and thoracic esophagus, a flow probe surrounding the thoracic esophagus, and arterial and venous catheters. In response to an intravenous infusion of sodium nitroprusside, fetal mean arterial blood pressure decreased from 50.8 +/- 3.6 to 41.7 +/- 3.8 mmHg. Fetal plasma renin activity (5.0 +/- 1.4-25.1 +/- 10.3 ng.ml-1.h-1) and arginine vasopressin (5.6 +/- 4.5-26.3 +/- 21.0 pg/ml) increased, while fetal swallowing electromyogram activity (7.3 +/- 1.1-1.9 +/- 0.3 swallows/10 min) and esophageal flow (5.5 +/- 3.1-1.2 +/- 0.9 ml/10 min) significantly decreased during the nitroprusside infusion. These results indicate a suppression of fetal swallowing in response to systemic hypotension despite stimulation of the renin-angiotensin system.

Ovine fetal cardiorespiratory response to nicardipine

Nicardipine, a calcium antagonist associated with decreased uterine blood flow in near-term pregnant rabbits and fetal asphyxia after maternal administration in the rhesus monkey and sheep, was infused directly to the fetus in six chronically prepared pregnant ewes at 128 days' gestation. Changes in fetal mean arterial and diastolic blood pressure levels at 2 and 30 minutes after bolus injection of 50 N,g were minimal; by 60 minutes these values had returned to preinfusion levels. No significant changes were observed after infusion of 100 wg of nicardipine. Fetal heart rate, fetal arterial blood gas values, and maternal cardiovascular variables did not change at either dose. Fetal plasma concentrations of nicardipine were 78 ± 28 ng/ml and 114 ± 48 ng/ml at 30 minutes after infusion of 50 wg and 100 Wg, respectively, well within the range previously reported to be associated with fetal asphyxia. These data suggest that the previously reported fetal acidosis from maternal infusion of nicardipine may be primarily due to a decrease in maternal uterine blood flow rather than a direct fetal effect of the drug.

Acidemia stimulates ACTH, vasopressin, and heart rate responses in fetal sheep

Adrenocorticotropic hormone (ACTH), arginine vasopressin (AVP), and renin responses to hemorrhage are highly correlated to the hemorrhage-induced decreases in arterial pH. The present study was designed to test the responses of these three systems to acute fetal acidemia, produced by intravenous infusion of H+. HCl was infused into chronically catheterized fetal sheep at rates of 0.02 (n = 5), 0.10 (n = 6), and 0.50 (n = 5) meq/min. Infusions at rates of 0.10 and 0.50 meq/min significantly decreased fetal arterial pH and increased arterial PCO2. Fetal heart rate and plasma concentrations of ACTH, cortisol, and AVP were significantly increased during infusion of HCl at 0.5 meq/min. Neither fetal plasma renin activity nor fetal arterial blood pressure was significantly altered by any of the infusions. The results of these experiments suggest that fetal ACTH, AVP, and heart rate are stimulated by decreases in arterial pH and/or increases in arterial PCO2. We speculate that these responses are chemoreceptor mediated, although we cannot distinguish the apparent relative roles of peripheral and central chemoreceptors on the basis of the present study.

Adverse effects of maternally administered lidocaine on the asphyxiated preterm fetal lamb.

Lidocaine was infused at a constant rate of 0.1 mg.kg-1.min-1 for 180 min into 12 chronically prepared pregnant sheep while asphyxia, induced by partial umbilical cord occlusion, was maintained in the premature fetus (80% of gestation). In five similar preparations saline instead of lidocaine was infused into the mother for 180 min. Maternal and fetal arterial blood pressure, heart rate, pHa, PaCO2, and PaO2 were monitored, and fetal cardiac output and the distribution of blood flow to fetal organs were measured, using labeled microspheres, before and after asphyxia and again after maternal infusion of lidocaine or saline. Maternal and fetal arterial blood and maternal urine were obtained at intervals for determination of lidocaine concentrations and urinary drug clearance. At the end of infusion, these animals were killed and tissues dissected for determination of lidocaine concentrations and organ blood flow. Maternal and fetal lidocaine plasma concentrations at steady state were 2.32 +/- 0.12 and 1.23 +/- 0.17 microgram/ml, respectively, similar to those seen during human epidural anesthesia. Asphyxia resulted in a significant drop in fetal heart rate and increased blood flow to the brain, heart, and adrenals. Asphyxia and saline did not produce additional deterioration of the fetus, but asphyxia and lidocaine led to a significant increase in PaCO2 and decreases in pHa, mean arterial pressure, and blood flows to the brain, heart, and adrenals. It is concluded that the immature fetus loses its cardiovascular adaptation to asphyxia when exposed to clinically acceptable plasma concentrations of lidocaine obtained transplacentally from the mother.

Role of endogenous opioids in the cardiovascular responses to asphyxia in fetal sheep.

Intravenous administration of the opioid receptor antagonist naloxone to asphyxiated fetal sheep increases the arterial blood pressure. We examined the hypothesis that endogenous opioids modify the cardiac output distribution during asphyxia due to changes in the vascular resistance of some fetal organs. Thirteen fetal sheep (0.8-0.9 of gestation) were chronically catheterized. Fetal asphyxia was induced by reducing the uterine blood flow with an inflatable occluder around the common internal iliac artery to approximately 50% of control for 40 min. Naloxone solution or the solvent alone was added for the last 20 min. Asphyxia caused hypertension, and the fetal arterial blood pressure further increased when asphyxiated fetuses received naloxone. Heart, brain, and adrenal blood flows increased due to the increase in blood pressure, with no changes in their vascular resistances. In contrast, kidney and carcass blood flows decreased, and their vascular resistances increased. We conclude that endogenous opioids inhibit the vasoconstriction of these vascular beds during fetal asphyxia.

The Effect of Nitrendipine (NIT) on Maternal and Fetal Blood Pressure, Uterine Blood Flow, and Blood Gas Status in Pregnant Sheep

Ewes of between 126-134 days of gestation (term 147 days) were anesthetized and underwent vascular cannula placement in the maternal and fetal jugular vein and carotid artery. A flow probe was placed around the uterine artery supplying the pregnant horn. A median of 7 days after surgery, the effect of nitrendipine (NIT) (2-8 micrograms/kg/min in stepwise increments of 30 min each followed by a 2-h recovery period) on maternal and fetal systemic arterial blood pressure (BP), heart rate (HR), the uterine blood flow (UBF), and blood gas tensions was determined (n = 5 experiments). Control experiments (n = 4) in which vehicle only was infused were also performed. The infusion of NIT was associated with a small fall in maternal systolic BP and a progressive fall in maternal diastolic BP (p less than 0.01, less than 0.001; two-way ANOVA); UBF did not change. Fetal systolic BP actually rose during the NIT infusion (p less than 0.02) but there was no difference in fetal diastolic BP. Both maternal and fetal HR rose in the NIT group. Fetal pH remained very stable throughout as did PaCO2. Fetal PaO2 fell somewhat during the recovery stages in both NIT and control groups. There is considerable interest in the possible use of calcium channel blockers in treating pregnancy-induced hypertension. These preliminary experiments provide no evidence in conflict with such a use.

Maternal and Fetal Effects of Epinephrine in Gravid Ewes

Intravenous cannulation by an epidural catheter may complicate epidural anesthesia. Local anesthetic solutions containing epinephrine produce tachycardia and hypertension when given intravenously and may identify intravenous placement. The authors studied the maternal and fetal effects of intravenous epinephrine-containing solutions in ten chronically instrumented gravid ewes. While continuously monitoring maternal and fetal effects, epinephrine 5, 10, or 20 micrograms iv bolus was injected. Solutions of bupivacaine 5 mg and bupivacaine 5 mg combined with epinephrine 10 micrograms given iv were also examined. All epinephrine-containing solutions produced a significant increase (P less than 0.001) in maternal mean arterial pressure, which returned to baseline after 1 min. Maternal heart rates decreased transiently and returned to baseline after 1 min. All epinephrine-containing solutions decreased uterine blood flow (UBF) (P less than 0.001), and, for doses of 10 to 20 micrograms, this decrease lasted more than 3 min. Fetal heart rate and mean arterial blood pressure did not change following any test solution, nor did maternal or fetal arterial blood gas values. The authors conclude that small intravenous boluses of epinephrine decreased UBF in these animals.