Sinusoidal fetal heart rate pattern following intrauterine fetal transfusion.

Two patients with severe rhesus isoimmunization had sinusoidal fetal heart rate patterns following intrauterine fetal transfusion. A consistent temporal relationship between fetal transfusion and sinusoidal fetal heart rate pattern was observed. Survival of a fetus who had a sinusoidal fetal heart rate pattern after each of three transfusions suggests that this pattern may not be ominous when observed transiently after fetal transfusion.

Fetal acid-base state following spinal or epidural anesthesia for cesarean section.

The authors compared fetal acid-base state and maternal blood pressure response in 111 women undergoing repeat cesarean section with either epidural or spinal anesthesia. Fetal umbilical acidemia (umbilical venous pH less than 7.25 or umbilical arterial pH less than 7.20) was more commonly observed following spinal anesthesia with a preanesthetic fluid load of 500 to 999 ml (20% of cases) than with epidural anesthesia (4% of cases. P > .05, chi 2). The incidence of fetal acidemia following spinal anesthesia was similar to that following epidural anesthesia when 1000 to 1500 ml of fluid was infused prior to spinal anesthesia. The maximum reduction in systolic blood pressure following spinal anesthesia was not related to preanesthetic fluid load; however, in cases of severe hypotension the hypotensive episode was shorter and easier to treat when the preanesthetic fluid load was 1000 to 1500 ml rather than 500 to 999 ml. These data suggest that women receiving spinal anesthesia for repeat cesarean section should be given an intravenous fluid load of 1 liter or more.

Effect of terbutaline on cardiovascular state and uterine blood flow in pregnant ewes.

The cardiovascular and uterine hemodynamic effects of terbutaline, a beta-adrenergic receptor stimulant and labor inhibiting agent, were evaluated in the chronically instrumented, near-term pregnant ewe. The administration of terbutaline in the dose range required for labor inhibition in this species resulted in a mild maternal tachycardia and increase in pulse pressure without significant changes in uterine blood flow; uterine vascular resistance; or systolic, diastolic, or mean blood pressures. With infusion rates of terbutaline in excess of those required for labor inhibition, significant increases in maternal heart rate, pulse pressure, and systolic blood pressure were observed. Diastolic blood pressure decreased significantly during the higher infusion rates; however, uterine blood flow was unaffected. The minimal cardiovascular and uterine blood flow was unaffected. The minimal cardiovascular and uterine hemodynamic effects noted with the administration of terbutaline in the dose range necessary for labor inhibition indicate that this agent may possess advantages over several others currently in use for the treatment of premature labor.

Comparison of continuous transcutaneous Po2 measurement with intermittent arterial Po2 determinations in fetal lambs.

This study determined the validity of transcutaneous Po2 (tcPo2) versus Pao2 determinations in the sheep fetus. In 7 fetal lambs catheters were placed in the carotid artery and the trachea, and ECG leads and a tcPo2 electrode were attached. Intermittently determined Pao2 values were compared to continuously recorded tcPo2 values. Fetal tcPo2 values ranging from 12 to 29 mmHg were achieved by changing the gas mixture the ewe breathed or by inflation of a balloon catheter in the maternal aorta. Transcutaneous Po2 correlated strongly with Pao2 (r = .91). These studies indicate that the tcPo2 electrode precisely and accurately reflects Pao2 in the fetal lamb. Limitations of tcPo2 measurements regarding prolonged attachment of the electrode to the fetal skin as well as fetal skin tolerance to the heat of the electrode have been identified. With this electrode the changes in oxygen tension can be compared with changes in fetal cardiovascular variables, eg, heart rate, blood pressure, and ECG, for a better understanding of the effects of hypoxemia on the fetus.

Fetal compensatory responses to reduced oxygen delivery.

I have described how various maternal and fetal conditions can affect fetal oxygen delivery. It is clear from much of the recent experimental evidence that fetal oxidative metabolism can be sustained despite reductions in fetal O2 delivery of 40-50%. As long as fetal oxygen reserves are not depleted, fetal metabolic functions will continue aerobically, even though fetal hypoxemia is present. As O2 reserves are exhausted in some tissues, fetal hypoxemia will be associated with tissue hypoxia, the net result of which will be anaerobic metabolism, lactic acidosis, and tissue death. Whether a fetus is adequately oxygenated or not is a function of the quantity of oxygen reserve available. A fetus with a substantial oxygen reserve can compensate fully for most interferences in its oxygen supply and can maintain oxidative metabolism under a variety of conditions. In contrast, a fetus with minimal oxygen reserves will not tolerate even the mildest degree of O2 deficiency without developing tissue hypoxia or even death in utero. The quantity of O2 delivered to the fetus, rather than the specific condition that may be adversely affecting O2 delivery, is the important determinant of the adequacy of fetal oxygenation.

Regulation of blood flow through the ductus venosus.

The ductus venosus, which is situated within the liver parenchyma, is a vascular shunt unique to the fetal and neonatal circulations. In fetal life, the ductus venosus allows variable portions of the umbilical and portal venous blood flows to bypass the liver microcirculation. After birth, when the umbilical circulation ceases, blood flow through the ductus venosus decreases substantially. The purposes of this review are to summarize the data currently available on the regulation of ductus venosus blood flow in fetal and neonatal life and to identify those factors that affect ductus venosus closure after birth. Most recent experiments indicate that mechanical factors exert the major influence on the fetal ductus venosus shunt. In the fetal sheep, for example, pressure and resistance differences across the liver are important determinants of the umbilical venous blood flow through the ductus venosus. In addition, ductus venosus blood flow can passively in response to alterations in the systemic circulation. Shortly after birth, blood flow and blood pressure in the umbilical sinus decrease abruptly. This causes the orifice of the ductus venosus to retract and narrow, resulting in functional closure of the vascular shunt. Permanent structural closure, consisting of connective tissue deposition within the entire ductus lumen, starts within days after birth and is completed by 1-3 months of age.

Preferential streaming of ductus venosus blood to the brain and heart in fetal lambs.

In 16 chronically prepared fetal lambs we compared the systemic distribution of ductus venosus blood flow with that of abdominal inferior vena caval blood by simultaneously injecting microspheres labeled with different radionuclides into an umbilical vein and into the abdominal inferior vena cava. A significantly greater proportion of ductus venosus blood flow than of abdominal inferior vena caval blood flow supplied the brain, heart, and upper body; this resulted from streaming of ductus venosus blood flow within the thoracic inferior vena cava with preferential direction of that blood flow through the foramen ovale. Blood flows to upper and lower body structures and placenta calculated from umbilical venous microsphere injections and reference arterial blood samples did not differ from those computed fromabdominal inferior vena caval injections and reference samples. Thus, despite streamline blood flow within the fetal thoracic inferior vena cava, organ blood flows can be accurately measured with either an umbilical venous or an abdominal inferior vena caval injection of microspheres when either is combined with the appropriate reference arterial blood samples.

Fetal intestinal oxygen consumption at various levels of oxygenation.

In seven chronically catheterized fetal lambs, blood flow and oxygen consumption (VO2) in the combined small and large intestines were determined at various oxygen concentrations in fetal arterial blood (CaO2). Intestinal blood flow (Qi) was measured with the radioactive-microsphere technique; intestinal oxygen delivery (DO2 = Qi X CaO2), VO2 [Qi X C(a-v)O2, where oxygen extraction [C(a-v)O2/CaO2] were computed with the Fick equation. Compared with normally oxygenated fetuses (CaO2 greater than 6.6 ml/dl), moderately hypoxemic fetuses (CaO2 = 4.4-6.6 ml/dl) had decreased intestinal DO2, increased oxygen extraction, and no change in intestinal VO2, Qi, or mesenteric-venous pH and base excess. During severe fetal hypoxemia (CaO2 less than 4.4 ml/dl), DO2 decreased further while oxygen extraction increased substantially. Intestinal VO2 dropped, however, because the rise in oxygen extraction could no longer completely compensate for the reduced DO2. With severe hypoxemia, Qi and mesenteric-venous pH and base excess also fell. These data indicate that the fetal intestinal tract is able to meet its oxygen needs during hypoxemia until a critically low level of oxygenation is reached. Below this level intestinal oxygenation becomes inadequate, and anaerobic metabolism ensures.

Oxygen consumption by the gastrointestinal tract and liver in conscious newborn lambs.

We determined blood flow to and O2 consumption (VO2) by the gastrointestinal tract (GI) and liver and also measured cardiac output and whole-body VO2 in nine chronically catheterized unanesthetized lambs (7-16 days of age). Blood flows were calculated with the radionuclide-labeled microsphere technique, and blood O2 contents were measured with an O2 content analyzer. During the fasting state, GI blood flow was 58 +/- 4 (means +/- SE) ml.min-1.kg body wt-1; GI VO2 was 1.4 +/- 0.1 ml O2.min-1.kg-1. Neonatal GI VO2 was linearly related to both GI blood flow and O2 delivery (DO2). GI O2 extraction [(VO2/DO2).100] averaged 28% and did not vary with blood flow or DO2. Liver blood flow was 73 +/- 4 ml.min-1.kg-1 (271 +/- 23 ml.min-1.100 g liver-1), and liver VO2 was 2.0 +/- 0.1 ml O2.min-1.kg-1 (7.3 +/- 0.5 ml O2.min-1.100 g-1). Hepatic O2 extraction varied from 18 to 81% . VO2 by the neonatal liver did not correlate with liver blood flow or DO2. Hepatic O2 extraction, however, was inversely related to liver DO2. Our data indicate that the gastrointestinal tract and liver of the unanesthetized newborn animal exhibit O2 demands 1.5-3 times those reported in the adult. The neonatal gastrointestinal tract meets its O2 demands with a comparatively large blood flow and O2 delivery, whereas the neonatal liver provides for its O2 requirements by varying its O2 extraction.

Blood flow and oxygen delivery to fetal organs as functions of fetal hematocrit.

The purpose of our experiments was to relate blood flow and oxygen delivery (blood flow x arterial blood oxygen concentration) to fetal organs as functions of fetal hematocrit. In 12 chronically catheterized fetal lambs, we observed two patterns of responses of fetal organs and tissues to isovolemic alterations in fetal hematocrit from 12% to 55%. In group 1 organs (brain, heart, adrenal glands), blood flows increased as hematocrit was either raised or lowered from normal such that oxygen delivery to these organs was stable over the entire range of hematocrits studied. In group 2 organs (gastrointestinal tract organs, spleen, kidneys, placenta, and carcass), blood flows varied little over the range of hematocrits from 12% to 40% or 45% but decreased at hematocrits greater than or equal to 40% to 45%. Because of these flow responses, oxygen delivery to these organs and tissues was maximal at hematocrits ranging from 32% to 38%. Our data indicate that the various organs of the unanesthetized fetal lamb respond in different ways to alterations in hematocrit. It is of particular interest that, in the great majority of the organs of the fetus, oxygen delivery is maximal at hematocrits considered normal for the fetal lamb in utero.

Hepatic oxygenation during arterial hypoxemia in neonatal lambs.

We identified the effects of reductions in arterial blood oxygen concentration from 15.0 to 4.0 ml O2/dl blood on hepatic blood flow, oxygen delivery, oxygen consumption and oxygen extraction in nine chronically catheterized lambs, 9 +/- 1 (SD) days of age. Hypoxemia was induced by administering a gas mixture low in oxygen to the unanesthetized lambs. Hepatic blood flow was measured with the radioactive microsphere technique; hepatic oxygen delivery, extraction, and consumption were calculated with modifications of the Fick principle. When the lambs breathed room air, hepatic blood flow was 235 +/- 30 ml/min/100 gm (mean +/- SD); hepatic oxygen delivery, 24.6 +/- 3.0 ml O2/min/100 gm; oxygen extraction, 37 +/- 11%; and hepatic oxygen consumption, 8.9 +/- 1.9 ml O2/min/100 gm. As arterial blood oxygen concentration was reduced from 15 to 6.5 ml O2/dl blood, hepatic blood flow did not change. When the concentration was less than 6.5 ml O2/dl, hepatic blood flow decreased as a result of a decrease in portal blood flow. Hepatic oxygen delivery decreased in the whole range of arterial blood oxygen concentrations studied. Despite reductions in oxygen delivery of up to 50%, hepatic oxygen consumption did not fall because hepatic oxygen extraction increased as compensation. Oxygen consumption, however, was stable only when hepatic blood flow did not change in response to hypoxemia. When hepatic blood flow fell, hepatic oxygen consumption also fell. Our data indicate that hepatic oxygen requirements can be met during hypoxemia by increases in hepatic oxygen extraction as long as hepatic blood flow does not change. When hepatic blood flow falls, hepatic oxygen consumption decreases even though oxygen reserves are still present. These data indicate that hepatic oxygenation in the neonate, as in the adult, is dependent on stable hepatic perfusion rather than adequate oxygen supply.

Relationship of fetal oxygen consumption and acid-base balance to fetal hematocrit.

We evaluated the effects of alterations in fetal hematocrit on fetal oxygenation in 10 chronically catheterized fetal lambs. Hematocrit was varied from 10% to 55% by slow isovolemic exchange transfusions with plasma or packed red blood cells obtained freshly from donor fetuses. At each hematocrit studied, we measured umbilical blood flow (Qumb) and the oxygen concentrations in umbilical venous blood (CUVO2) and arterial blood (CAO2) and calculated fetal oxygen delivery (Qumb X CUVO2), oxygen extraction [(CUVO2 - CAO2)/CUVO2], and oxygen consumption [Qumb (CUVO2 - CAO2)]. Fetal oxygen delivery was maximal at a fetal hematocrit of 33% (mean oxygen delivery = 23 ml of oxygen per minute per kilogram of fetus) and decreased as hematocrit was raised or lowered from that value. Despite these reductions in oxygen delivery, fetal oxygen consumption was relatively stable (at about 7 ml of oxygen per minute per kilogram) at hematocrits ranging from about 16% to 48% because of compensatory increases in fetal oxygen extraction. Regardless of whether oxygen delivery decreased because of anemia or polycythemia, fetal oxygen consumption was maintained as long as oxygen delivery was greater than about 14 ml of oxygen per minute per kilogram of fetus. When oxygen delivery was less than 14 ml of oxygen per minute per kilogram, fetal oxygen consumption fell while arterial blood base deficit increased, indicating that oxygen supply was inadequate for fetal oxygen demands. These results indicate that fetal aerobic metabolism can be sustained over a wide range of fetal hematocrits. Furthermore, our data support the concept that the level of fetal oxygen delivery is an important determinant of the adequacy of fetal oxygenation.

Effects of varying hematocrit on intestinal oxygen uptake in neonatal lambs.

We chronically catheterized 15 newborn lambs (9.5 +/- 2.8 days) and measured intestinal blood flow (Qi) by the radionuclide microsphere technique at hematocrit levels ranging from 10 to 55%. Seven animals were made progressively anemic and eight polycythemic by means of exchange transfusions. Using the Fick principle, we calculated intestinal oxygen delivery (Di o2), oxygen consumption (Vi o2), and oxygen extraction. Initial base-line values were Qi = 195.5 ml . min-1 . 100 g intestine-1, Di o2 = 22.1 ml . min-1 . 100 g-1, Vi o2 = 4.8 ml . min-1 . 100 g-1, and O2 extraction = 22.5%. As the hematocrit was lowered, Di o2 decreased and O2 extraction increased and vice versa when the hematocrit was raised. Vi o2 remained constant, but Qi did not correlate with changes in hematocrit. However, intestinal blood flow, as a percent distribution of total blood flow, decreased with lower hematocrit levels. At no time was there any evidence of anaerobic metabolism as measured by excess lactate production. Our data indicate that the intestines of neonatal lambs are capable of maintaining their metabolic needs over a wide range of oxygen availability induced by a changing hematocrit. The primary mechanism is through alteration of oxygen extraction. Within the range of our experiments, no critically low oxygen availability was attained at which anaerobic metabolism became significant.

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.

Pharmacologic inhibition of preterm labor.

Preterm labor is responsible for a majority of cases of perinatal morbidity and deaths. Prevention of preterm labor is not usually possible; thus pharmacologic treatment is the only recourse available. Numerous agents have been used to treat preterm labor, but none has proved to be superior. This report reviews the current information available about the pharmacology of labor-inhibiting drugs and discusses the clinical approach to the management of preterm labor.

Effects of dexamethasone on leukocyte counts in pregnant sheep and fetal lambs.

In adult nonpregnant animals and human beings, glucocorticosteroids increase circulating leukocytes (predominantly neutrophils) and decrease lymphocytes, monocytes, and eosinophils. We were interested in studying effects of glucocorticoids on leukocyte counts during pregnancy to determine any differences between responses in the nonpregnant and pregnant states. After general anesthesia was administered, we placed catheters in a carotid artery and a jugular vein in pregnant sheep and in fetal lambs. Six days after surgery, we administered dexamethasone intravenously to the mother (0.2 mg. per kilogram) or to the fetus (0.06 mg. per kilogram) and obtained maternal and fetal jugular venous blood samples immediately before (control) and 3, 6, 12, 24, 48, and 72 hours after steroid injection. Administration of dexamethasone to the mother significantly increased total leukocyte and neutrophil counts (leukocytes per cubic millimeter blood) and decreased lymphocyte and eosinophil counts, but it did not change monocyte counts. Leukocyte counts returned to control values within 48 hours. Administration of dexamsthasone to the fetus rapidly increased total leukocyte and neutrophil counts, decreased monocyte and eosinophil counts, and had not effect on lymphocyte counts. Fetal leukocyte counts returned to control values by 24 hours after dexamethasone injection. Our results suggest that maternal and fetal leukocytes can respond to glucocorticoids as they do in the adult nonpregnant state.

Lack of a critical cardiac output and critical systemic oxygen delivery during low cardiac output in the third trimester in the pregnant sheep.

OBJECTIVE: We sought to determine whether a critical cardiac output and oxygen delivery exist in normal pregnancy. We also sought to determine the role of fetoplacental oxygen demand on maternal oxygen transport variables in response to decreased maternal cardiac output. STUDY DESIGN: We studied 10 adult female sheep, 5 nonpregnant and 5 pregnant. We placed a flow-directed thermodilution catheter in the pulmonary artery and a balloon-tipped catheter in the right atrium of the sheep. We also placed a catheter for pressure monitoring and blood sampling in the descending thoracic aorta in both the mother and fetus. We decreased maternal cardiac output by incremental inflation of the right atrial balloon. We measured maternal cardiac output by intravenous bolus thermodilution technique. We also measured maternal and fetal acid-base status and serum lactate concentrations. We calculated a variety of maternal cardiorespiratory variables, including systemic oxygen delivery, systemic oxygen consumption, and fractional whole body tissue oxygen extraction. RESULT: The nonpregnant sheep displayed a critical cardiac output below which there was an abrupt decrease in oxygen consumption. In contrast, there was no critical level of cardiac output in the pregnant sheep. Maternal oxygen consumption was linearly dependent on cardiac output. Maximum fractional oxygen extraction was significantly lower in the pregnant sheep than in the nonpregnant sheep. CONCLUSION: States of low cardiac output in the pregnant sheep are associated with a lack of a critical cardiac output; the flow-dependent oxygen consumption observed is the result of either an impairment in tissue oxygen extraction or some degree of metabolic arrest or a combination of both. If this unique cardiac output-oxygen consumption relationship is seen in human pregnancy, it could have significant implications in the care of the critically ill obstetric patient.

Effect of betamethasone on analysis of amniotic fluid in the rhesus-sensitized pregnancy.

Betamethasone was administered to six rhesus-sensitized pregnant women carrying seven fetuses in an attempt to accelerate fetal pulmonary maturation. A reduction in optical density of amniotic fluid at 450 mmu was observed in all cases following steroid therapy; however, only minimal changes were noted in the lecithin-sphingomyelin ratio. The implications of these findings for the management of rhesus-sensitized pregnancies are discussed.

Effects of dexamethasone on maternal and fetal hemodynamic states and fetal oxygenation.

The effects of dexamethasone on maternal and fetal hemodynamic states and fetal oxygenation were determined in chronically instrumented unanesthetized pregnant ewes and fetal lambs. Intravenous injections of pharmacologic doses of dexamethasone to the mother failed to alter maternal blood pressure, heart rate, blood flow in the uterine artery supplying the pregnant horn, or uterine vascular resistance. Direct administration of dexamethasone to the fetus had no effect on fetal blood pressure, heart rate, acid-base state, or oxygenation. Furthermore, direct fetal administration of dexamethasone did not produce premature parturition.