Biomedical subjects

A M Rudolph

Publications and source records attributed to A M Rudolph.

At least 55 records · Page 3Linked to original sources

PubMed1991

Effects of reducing uterine blood flow on fetal blood flow distribution and oxygen delivery.

We examined the effect of graded reduction in uterine blood flow on distribution of cardiac output and oxygen delivery to fetal organs and venous blood flow patterns in 9 fetal sheep using the radionuclide-labeled microsphere technique. We reduced uterine blood flow in two steps, decreasing fetal oxygen delivery to 70% and 50% of normal, and compared the results with those from a similar study from our laboratory on graded umbilical cord compression. With 50% reduction in fetal oxygen delivery, blood flow and the fraction of the cardiac output distributed to the brain, heart, and adrenal gland increased and that to the lungs, carcass, skin, and scalp decreased. Oxygen delivery to the brain and myocardium was maintained, while that to the adrenal doubled, and that to the brain stem increased transiently. The decrease in oxygen delivery to both carcass and lower body segment correlated linearly with oxygen consumption (P less than 0.001). The proportion of umbilical venous blood passing through the ductus venosus increased from 44.6% to 53% (P less than 0.05). The preferential distribution of ductus venosus blood flow through the foramen ovale to the heart and brain increased, but that to the upper carcass decreased so that ductus venosus-derived blood flow to the upper body did not change. Hence, the oxygen delivered to the brain from the ductus venosus was maintained, and that to the heart increased 54% even though ductus venosus-derived oxygen delivery to the upper body fell 34%. Abdominal inferior vena caval blood flow and its contribution to cardiac output decreased, but the proportion of the abdominal inferior vena caval blood distributed through the foramen ovale also increased from 23.0 to 30.9%. However, the actual amount of inferior vena caval blood passing through the foramen ovale did not change. There was a 70% fall in oxygen delivery to the upper body segment from the inferior vena cava. A greater portion of superior vena caval blood was also shunted through the foramen ovale to the upper body, but the actual amounts of blood and oxygen delivered to the upper body from this source were small. Thus, graded reduction of uterine blood flow causes a redistribution of fetal oxygen delivery and of venous flow patterns, which is clearly different from that observed previously during graded umbilical cord occlusion.

Animals↗

PubMed1991

Cortisol induces perinatal hepatic gluconeogenesis in the lamb.

To examine the influence of a prenatal increase in plasma cortisol concentration on perinatal initiation of hepatic gluconeogenesis, we infused cortisol into seven fetal sheep at 137-140 days gestation. 14C-Lactate provided tracer substrate for estimation of gluconeogenesis. We measured hepatic blood flow using radionuclide-labeled microspheres. After delivery, fetal arterial blood glucose concentration (1.33 +/- 0.4 mmol/l) increased transiently, but returned to fetal levels within 1 h after delivery. Substantial hepatic gluconeogenesis was induced in the fetus after cortisol infusion, averaging 23.4 +/- 12.2 mumol/min/100 g liver (7.8 +/- 4.4 mumol/min/kg fetal weight). Fetal hepatic glucose output was 44.4 +/- 17.7 mumol/min/100 g liver. Hepatic glucose output did not change after delivery; estimated gluconeogenesis decreased immediately, then increased by 6 h after delivery. Lactate supply to the liver fell substantially, from 1.1 +/- 0.4 mmol/min/100 g in the fetus to 0.24 +/- 0.09 at 1 h after delivery. Lactate flux across the liver decreased from 75.3 +/- 23 mumol/min/100 g in the fetus to 20.2 +/- 15.7 at 1 h after delivery. Hepatic lactate flux was significantly related to gluconeogenesis (r = 0.734, P = 0.0001). We conclude that cortisol induces substantial hepatic gluconeogenesis in fetal sheep near term. After delivery, there appears to be a transient decline in gluconeogenesis from lactate, which may be secondary to limited hepatic oxygen and substrate supply. Onset of gluconeogenesis in the fetus fails to sustain increases in either fetal or postnatal blood glucose concentrations.

Animals↗

PubMed1991

Effects of maternal fasting on hepatic gluconeogenesis and glucose metabolism in fetal lambs.

In unstressed, normoglycaemic fetal lambs, the liver produces little glucose, and gluconeogenesis is insignificant. Indirect measurements have suggested that the fetus may produce glucose endogenously during hypoglycaemia induced by prolonged maternal starvation. In eight fetal lambs we directly measured total and radiolabelled substrate concentration differences across the liver to determine whether the fetal liver produces glucose after four days of fasting-induced hypoglycaemia. Simultaneously we measured umbilical glucose uptake and fetal glucose utilization. Glucose concentrations in ewes (1.78 +/- 0.44 mmol.-1) and fetuses (0.61 +/- 0.17 mmol.l-1) were decreased. Fetal glucose utilization rate (21.7 +/- 8.9 mumol.min-1.kg-1) was not significantly different from umbilical glucose uptake (17.2 +/- 8.9 mumol.min-1.kg-1). Hepatic glucose production (8.9 +/- 17.2 mumol.min-1.100 g-1) and gluconeogenesis (6.1 +/- 4.4 mumol.min-1.100 g-1) were present, but could account for only 13% and 8% of fetal glucose requirements, respectively. To determine whether glucose output by the fetal liver was limited by substrate availability, we infused lactate, acetate, and acetone into the umbilical veins of four fasted animals, increasing hepatic substrate delivery. Hepatic glucose output did not increase during infusion of gluconeogenic substrates, indicating that substrate availability did not limit gluconeogenesis. We conclude that the gluconeogenic pathway is intact in late-gestation fetal lambs and that the fetal liver is capable of gluconeogenesis. However, the primary change in fetal metabolism during maternal starvation is the reduction in fetal glucose utilization, obviating the need for substantial hepatic glucose production. The factors stimulating this modest increase in fetal hepatic glucose production remain to be elucidated.

Animals↗

PubMed1991

Cardiovascular responses to acute, severe haemorrhage in fetal sheep.

In adults, the responses to acute haemorrhage vary greatly depending on the amount of blood lost. While many studies have documented fetal responses to mild haemorrhage, fetal responses to severe haemorrhage are not known. In this study we examined the effect of acute, severe haemorrhage in fetal lambs. Despite the severity of haemorrhage, we found that mean arterial blood pressure was restored within 2 min, and heart rate was restored within 30 min. This restoration of blood pressure and heart rate was facilitated by an increase in peripheral vascular resistance mediated in part by secretion of catecholamines and plasma renin. In addition, about 40% of the shed blood volume was restored within 30 min by fluid from either the fetal interstitium or placenta. The PO2 of umbilical venous blood increased from 33 +/- 9 mmHg to 49 +/- 17 mmHg 2 min post-haemorrhage, and to 47 +/- 15 mmHg 30 min post-haemorrhage. However, this increase was not sufficient to offset the fall in both haemoglobin concentration and umbilical-placental blood flow, so that oxygen delivery decreased from 21.1 +/- 5.5 ml/min per kg to 9.1 +/- 5.2 ml/min per kg 2 min post-haemorrhage, and 14.1 +/- 9.2 ml/min per kg 30 min post-haemorrhage. Because of this decrease in oxygen delivery, oxygen consumption fell and a metabolic acidemia ensued. Nevertheless, oxygen delivery to the heart and brain was maintained because hepatic vasoconstriction diverted more of the well oxygenated umbilical venous return through the ductus venosus. Although the fetus was able to tolerate acute loss of 40% of blood volume, larger volumes of haemorrhage resulted in fetal death.

Animals↗

PubMed1990

Venous and hepatic vascular responses to indomethacin and prostaglandin E1 in the fetal lamb.

Evidence is accumulating that prostaglandins affect the tone of the ductus venosus. Therefore prostaglandins might alter the distribution of umbilical venous return between the ductus venosus and liver. We have examined the effect of indomethacin and prostaglandin E1 on the vascular resistance of the umbilical-placental circulation, ductus venosus, and liver in 14 chronically instrumented fetal lambs. We found that indomethacin caused a nearly twofold increase in the vascular resistance of both the ductus venosus and liver. Prostaglandin E1, administered 70 minutes after indomethacin at a dose of 0.41 +/- 0.09 (SEM) micrograms/min per kilogram of fetal weight, decreased umbilical-placental blood flow, increased the vascular resistance of the umbilical arteries and placenta, and reversed the elevation of the vascular resistances of the ductus venosus and liver. Because both indomethacin and prostaglandin E1 affected the resistances of the ductus venosus and liver to the same extent, it is unlikely that prostaglandins of the E series mediate the change in distribution of umbilical venous return between the ductus venosus and liver during fetal stress.

Alprostadil↗

PubMed1990

Stopping the biologic clock for globin gene switching.

The developmental switch from production of fetal (gamma) to adult (beta) globin occurs on a normally set biologic clock which proceeds even if expression of the adult (beta) globin genes is defective and produces little or no protein, as in the beta-thalassemias. Preventing or reversing the globin gene switch could provide a way of keeping the abnormal globin genes "silent" and maintaining expression of the fetal globin gene. We have identified a class of agents which, when present in elevated plasma concentrations during gestation, inhibits the gamma----beta-globin gene switch in developing humans. Further investigation has shown that butyric acid and related compounds can increase gamma-globin and decrease beta-globin expression in cultured erythroid cells of patients with beta-thalassemia. Butyrate compounds were therefore infused in an in vivo fetal animal model, and the globin switch was inhibited and even reversed in some fetal lambs. Histone hyperacetylation, which maintains active chromatin structure, and an effect on the gamma-globin promoter appear to be mechanisms of action involved. These data suggest that inhibiting expression of abnormal beta-globin genes by pharmacologic means may in the future be possible for treatment of individuals with beta-globin disorders.

Anemia, Sickle Cell↗

PubMed1990

Two-dimensional echocardiographic determination of ventricular volumes in the fetal heart. Validation studies in fetal lambs.

The determination of ventricular volumes in the fetal heart from two-dimensional echocardiography (2DE) may give a better estimate of fetal ventricular size than simple diameter measurements, but the accuracy of this method has not been established. In fetal lambs, we tested whether ventricular volume calculations from 2DE using a biplane Simpson's rule algorithm are accurate. Calculations of left and right ventricular end-diastolic volumes from 2DE were compared with cast volumes of these ventricles. Also, at different levels of left atrial pressure, left ventricular stroke volumes calculated from 2DE were compared with stroke volumes measured simultaneously by an electromagnetic flowmeter. There was a good correlation between volumes determined from 2DE (y axis) and from casts (x axis) for both the left (r = 0.92; y = 0.2 + 1.1x; SEE = 0.19 ml) and right ventricle (r = 0.90; y = 0.7 + 0.9x; SEE = 0.21 ml). Left ventricular stroke volumes calculated from 2DE correlated well with those measured by the electromagnetic flowmeter (r = 0.87; y = 0.2 + 0.9x; SEE = 0.27 ml). Thus, calculation of fetal ventricular volumes from 2DE images using a biplane Simpson's rule method is feasible and accurate.

Animals↗

PubMed1990

The effects of increasing mean arterial pressure on left ventricular output in newborn lambs.

We developed a preparation in which the mean arterial pressure of the newborn lamb is varied with little change in left ventricular preload. Seven lambs underwent balloon atrial septostomy and were instrumented with vascular catheters, an electromagnetic flow transducer on the aorta, and a balloon occluder on the aorta. Four different preload conditions were established by volume infusion or withdrawal. Aortic flow was measured continuously during gradual occlusion of the aorta. Curves relating mean left atrial pressure to stroke volume before balloon inflation showed a plateau, with little increase in stroke volume with increases in atrial pressure above 7 mm Hg. With balloon inflation, stroke volume decreased linearly with increases in mean arterial pressure. Curves relating left atrial pressure to stroke volume constructed at constant mean atrial pressure showed no plateau but showed continued increases in stroke volume as left atrial pressure was increased to 10 mmHg. When mean arterial pressure is constant, the Starling mechanism is operative in newborn left ventricles. The plateau in newborn lamb function curves is due to increases in mean arterial pressure that accompany volume infusion.

Animals↗

PubMed1990

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.

Amnion↗

PubMed1990

Changes in the pulmonary circulation during birth-related events.

At birth, pulmonary vascular resistance decreases dramatically, allowing pulmonary blood flow to increase and oxygen exchange to occur in the lungs. To determine the extent to which ventilation of the fetus's lungs, oxygenation of the lungs, and umbilical cord occlusion can account for this decrease in resistance, we studied 16 chronically instrumented, near-term sheep fetuses in utero. We performed the experiment in a sequential fashion: we first studied the effects of ventilation alone (without oxygenation) on pulmonary vascular resistance and blood flow, and then determined the additive effects of oxygenation and cord occlusion. We calculated pulmonary vascular resistance from measurements of vascular pressures and measurements of pulmonary blood flow obtained by injecting radionuclide-labeled microspheres. We found that ventilation alone caused a large but variable increase in pulmonary blood flow, to 401% of control, no change in pulmonary arterial pressure, and a doubling of left atrial pressure. Thus, pulmonary vascular resistance fell dramatically, to 34% of control. Oxygenation caused a modest further increase in pulmonary blood flow and a decrease in mean pulmonary arterial pressure, so resistance fell to 10% of control. Umbilical cord occlusion caused no further changes in pressure, flow, or resistance. Unexpectedly, the fetuses' pulmonary blood flow responses to ventilation fell into two groups: the mean increase was maximal in eight of the 16 fetuses but was only 20% of the cumulative increase in the other eight. We found no differences between the two groups of fetuses to explain their different responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Venous responses to hypoxemia in the fetal lamb.

The factors regulating umbilical venous return and its distribution between the ductus venosus and liver are poorly understood. This study was designed to determine where the major changes in resistance to umbilical venous return occur in response to fetal hypoxemia. In eight chronically-instrumented fetal lambs, during control and hypoxemic periods, we measured pressure in the descending aorta, extra-abdominal umbilical vein, portal sinus, and inferior vena cava; we also measured blood flow using radionuclide-labeled microspheres. During the control period, the umbilical arteries and placental vasculature accounted for 82% of total resistance to umbilical-placental blood flow, the umbilical veins for 11%, and the ductus venosus and liver for 7%. Hypoxemia increased resistance in the umbilical veins more than twofold, but did not affect resistance in the umbilical arteries or placenta. Although combined liver/ductus venosus resistance did not change, hepatic vascular resistance increased, and ductus venosus resistance decreased. We conclude that the major increase in resistance to umbilical venous return in response to hypoxemia resides in the umbilical veins. This increased resistance may improve maternal-fetal blood gas exchange by increasing the fetal surface area in the placenta.

Animals↗

PubMed1990

Comparative study of acetaminophen disposition in sheep at three developmental stages: the fetal, neonatal and adult periods.

The disposition of acetaminophen was studied in adult nonpregnant ewes, neonatal lambs, pregnant ewes and their fetal lambs following single intravenous bolus doses. Comparisons of the pharmacokinetic parameters of acetaminophen were made between sheep at different developmental periods to examine the developmental alteration in the physiological and biochemical processes governing drug disposition. The four groups of animals exhibited distinct and significant differences in the total clearance and metabolic clearances of acetaminophen and the renal clearances of the glucuronide and sulfate conjugates. Placental transfer of acetaminophen from fetus to mother serves as the dominant route of fetal removal or clearance of the drug.

Acetaminophen↗

PubMed1989

Butyric acid modulates developmental globin gene switching in man and sheep.

The developmental switch from production of fetal (gamma) to adult (beta) globin occurs on a normally set biologic clock which proceeds even if the adult (beta) globin genes are defective. Preventing or reversing the globin gene switch would be beneficial for subjects with abnormal beta globin genes. We have now identified a class of agents which, when present in elevated plasma concentrations during gestation, appears to inhibit the gamma beta globin gene switch in developing humans. Further investigation has shown that butyric acid and related compounds can increase gamma globin and decrease beta globin expression in erythroid cells cultured from subjects with diseases of abnormal beta globin. Butyrate compounds were therefore infused in an in vivo fetal animal model, and the globin switch was inhibited in most and reversed in some fetal lambs. These data suggest that inhibiting expression of abnormal beta globin genes may be possible in future generations. Histone modification may be a mechanism of action involved. The developmental switch from production of gamma globin to beta globin results in significant morbidity when the beta globin genes are defective. The globin switch has therefore been extensively studied, appearing to be set on a biologic clock and proceeding despite the site of blood production and solely on the basis of gestational age. We previously found that this developmental gene switch is delayed in human fetuses developing in the presence of maternal diabetes. A number of metabolites present in abnormal concentrations in these infants were therefore tested for effects on globin expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

PubMed1989

The young lamb can increase cardiovascular performance during isoflurane anesthesia.

Cardiac output and myocardial blood flow decrease dramatically in a dose-dependent pattern in the young lamb during isoflurane anesthesia. This raises important questions about the ability of the young lamb to increase myocardial performance if oxygen delivery were compromised by a decrease in oxygen content during anesthesia and surgery. To investigate the ability of the young lamb to increase oxygen delivery during isoflurane anesthesia, the response to hypoxemia, which is known to increase myocardial performance, was studied in awake 1-week-old lambs. Mean systemic arterial pressure, heart rate, cardiac output, and regional distribution of blood flow were measured during three states: awake, 1.0 minimum alveolar concentration (MAC) of isoflurane in an FIO2 of 1.0, and 1.0 MAC of isoflurane in an FIO2 of 0.09. Stroke volume, total body and myocardial oxygen consumption, and fractional extraction of oxygen were calculated for the total body and for the myocardium. Isoflurane anesthesia decreased mean systemic arterial pressure (70 +/- 8 mmHg), heart rate (222 +/- 29 beats/min), and cardiac output (277 +/- 72 ml.kg-1.min-1) significantly (43 +/- 11 mmHg, 163 +/- 20 beats/min, 191 +/- 34 ml.kg-1.min-1). Hypoxemia returned heart rate to control (191 +/- 23 beats/min), increased stroke volume (1.71 +/- 0.2 ml/kg) above both control (1.23 +/- 0.2 ml/kg) and 1.0 MAC isoflurane levels (1.19 +/- 0.3 ml/kg), and increased cardiac output (325 +/- 61 ml.kg-1.min-1) above the level during 1.0 MAC isoflurane.

Anesthesia, General↗

PubMed1989

Responses to acute hypoxemia in fetal sheep at 0.6-0.7 gestation.

A majority of previous studies of fetal responses to acute hypoxemia has focused on the response of the sheep fetus greater than 120 days of gestation when many regulatory systems have been established. To assess the response of younger, less well-developed fetuses, we exposed two groups of fetal sheep (I, 84-91 days; II, 97-99 days gestational age) to acute hypoxemia by giving the ewe a gas mixture containing 9% O2 to breathe. We decreased descending aortic PO2 in both groups of fetuses [I, 24 +/- 6 to 14 +/- 3 (SD) Torr; II, 23 +/- 3 to 12 +/- 4 Torr] by a degree similar to that achieved in previous studies of fetuses greater than 120 days of gestation. Mean arterial blood pressure (I, 31 +/- 6; II, 40 +/- 3 Torr) did not change significantly from control values, and heart rate (I, 224 +/- 27; II, 203 +/- 16 beats/min) increased significantly in group II fetuses with hypoxemia. In group I and II fetuses, as in older fetuses, cerebral, myocardial, and adrenal blood flows, measured by the microsphere technique, increased, and pulmonary blood flow decreased. These responses mature early and are likely local vascular responses to decreases in oxygen content. Combined ventricular output and umbilical-placental blood flow decreased significantly in both groups. Unlike the response of the fetus greater than 120 days, acute hypoxemia did not decrease blood flow to the musculoskeletal and cutaneous circulations (group I only), gastrointestinal, or renal circulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Effects of increasing afterload on left ventricular output in fetal lambs.

Fetal ventricular performance has been considered limited because ventricular output does not increase with rapid volume expansion above mean left atrial pressures (mLAPs) of 5-7 mm Hg. To explore relations between preload, afterload, and stroke volume (SV) in the fetal left ventricle, we instrumented 126-129 days gestation fetal lambs with ascending aortic electromagnetic flow transducers, vascular catheters, and inflatable occluders around the aortic isthmus (n = 8) or descending aorta (n = 7). At 24-48 hours after surgery, blood was withdrawn or infused to reach various mLAPs. The aorta was then slowly occluded as aortic flow and mean arterial pressure (MAP) were measured continuously. Isthmus constriction produced linear decreases in SV as MAP increased; mLAP was unchanged. Descending aortic constriction produced no decrease in SV until high MAPs were reached. SV decreased as MAP increased further, and mLAP rose significantly. The curve relating mLAP and SV before constriction showed little increase in SV above mLAPs of 5-7 mm Hg; however, when curves were derived relating SV and mLAP at relatively constant MAPs, SV continued to increase even above an mLAP of 8-10 mm Hg. Our studies indicate that the fetal left ventricle responds to progressive increases in mLAP to at least 10 mm Hg. The lack of increase in SV above an mLAP of 5-7 mm Hg with rapid volume expansion is related to the concomitant increase in MAP and afterload.

Animals↗

PubMed1989

Effect of acute umbilical cord compression on hepatic carbohydrate metabolism in the fetal lamb.

Although the liver plays a central role in glucose homeostasis in the adult, its importance in fetal glucose homeostasis during acute reductions of substrate delivery is unknown. To examine this, we studied eight fetal lambs at 121 +/- 2 d gestation. We placed catheters in the descending aorta, inferior vena cava umbilical vein and the left (n = 6) or right (n = 2) hepatic vein, and a balloon occluder around the umbilical cord. At least 4 d after surgery, before and during umbilical cord compression, we measured blood oxygen saturation, glucose, lactate, and Hb concentrations, and blood flows using the radiolabeled microsphere technique. Gluconeogenesis was assessed by infusion of [U14C]lactate. Reducing umbilical flow by 50-60% from a control value of 181 +/- 20 mL/min/kg (mean +/- SD) caused a dramatic decrease in hepatic blood flow from 332 +/- 99 to 94 +/- 77 mL/min/100 g (p less than 0.05). Oxygen delivery to the fetus fell by 50% and that to the liver by 73%. However, hepatic O2 consumption was maintained by increased extraction. Glucose delivery to the liver fell from 67 +/- 24 to 20 +/- 13 mg/min/100 g (p less than 0.001), but lactate delivery did not change. In spite of the maintenance of lactate delivery, net hepatic lactate uptake fell significantly from 3.3 +/- 1.7 to 1.4 +/- 0.9 mg/min/100 g (p less than 0.05). This could account, in part, for the increase of blood lactate concentration from 16 +/- 4 to 27 +/- 7 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Changes in ovine hepatic circulation and oxygen consumption at birth.

The umbilical vein provides the majority of hepatic blood flow during fetal life. After birth, liver blood flow is derived from the hepatic artery and portal vein, but ductus venosus patency can alter portal venous blood flow to the liver. To characterize changes in hepatic blood flow and oxygen metabolism in the immediate perinatal period, we studied liver and ductus venosus blood flow in seven fetal sheep before and after birth using the radionuclide-labeled microsphere method. Hepatic blood flow fell from 423 +/- 117 (mean +/- SD) mL/min/100 g liver in the fetus to 144 +/- 73 by 2 h after delivery. Although portal venous blood flow increased progressively from 2 to 10 h (137 +/- 48 to 305 +/- 140 mL/min/100 g), because of increasing ductus venosus shunt flow, total hepatic blood flow did not change. Hepatic arterial flow was 46 +/- 24 mL/min/100 g at 2 h, providing 35% of total hepatic blood flow, and did not change over the next 8 h. Hepatic oxygen delivery fell after birth from 58 +/- 25 mL/min/100 g liver in the fetus to 21 +/- 11 at 2 h and then remained constant. Hepatic oxygen consumption was 7.3 +/- 2.6 mL/min/100 g liver in the fetus and ranged from 3.2 +/- 1.5 to 4.1 +/- 1.8 mL/min/100 g liver during the 10 h after birth. Loss of the umbilical-placental circulation at birth substantially reduces hepatic blood flow. Hepatic arterial flow does not increase to compensate for decreases in total hepatic blood flow. The persistent ductus venosus shunt compromises portal venous supply to the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗