Vascular responses of umbilical-placental circulation to vasodilators in fetal lambs.

It has been suggested that the umbilical-placental circulation is maximally vasodilated under normal conditions. To test this hypothesis, we investigated the effect of vasodilators on umbilical-placental vascular resistance. In nine chronically instrumented fetal lambs, catheters were placed in the descending aorta, umbilical artery, umbilical vein, and inferior vena cava. Umbilical-placental blood flow was measured by an electromagnetic flow probe placed around the common umbilical artery. Forskolin and nitroglycerin both dilated the umbilical-placental circulation, causing a dose-dependent decrease in umbilical-placental resistance to approximately 80% of baseline, indicating that the umbilical-placental circulation has some dilatory reserve. Both the adenosine 3',5'-cyclic monophosphate and the guanosine 3',5'-cyclic monophosphate mechanisms, which are directly stimulated by forskolin and nitroglycerin, respectively, are functional in the umbilical-placental circulation. However, the vasodilators prostacyclin and adenosine, which act through specific cell membrane receptors, have no effect on the umbilical-placental resistance. The inability of these agents to dilate the umbilical-placental circulation could be due to a lack of the appropriate receptors in the umbilical-placental vasculature.

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

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

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.

Umbilical and hepatic venous responses to circulating vasoconstrictive hormones in fetal lamb.

Acute fetal hypoxemia increases the vascular resistance of the umbilical veins as well as that of the liver. Because, at least in the human, the umbilical-placental circulation has no autonomic innervation, circulating hormones could well be responsible for this increase in umbilical-placental outflow resistance. In chronically instrumented fetal sheep, norepinephrine, epinephrine, vasopressin, and angiotensin II were infused in sequentially increasing doses into the descending aorta and vascular resistance to umbilical-placental blood flow was measured. Norepinephrine and epinephrine increased the vascular resistance of the umbilical veins in a dose-dependent manner. Both catecholamines also increased the vascular resistance of the liver, resulting in an increase in ductus venosus blood flow. In contrast, vasopressin and angiotensin II had no effect on umbilical-placental outflow resistance. Thus catecholamines may be responsible for the increase in the vascular resistance of the umbilical veins and liver in response to acute fetal hypoxemia.

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.

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.

Hemodynamic responses to alpha-adrenergic blockade during hypoxemia in the fetal lamb.

The mechanisms responsible for the increase in umbilical venous and hepatic vascular resistance during hypoxemia are poorly understood. To assess the relative importance of alpha-adrenergic receptors, we produced an acute, severe hypoxemia in chronically instrumented fetal sheep. While fetal arterial oxygen saturation was maintained at the same level, we then injected phentolamine, a selective alpha-adrenoreceptor blocker. We found that the hypoxemia-induced vasoconstriction of the umbilical veins and hepatic vasculature was reversed by alpha blockade. Thus, alpha-adrenergic stimulation is necessary to maintain vasoconstriction of the umbilical veins and hepatic vasculature during acute fetal hypoxemia. Furthermore, alpha-adrenergic stimulation is responsible for the hypoxemia-induced vasoconstriction of the gut, spleen, and lower carcass. Thus, the alpha-adrenergic system mediates important fetal hemodynamic adaptations to acute hypoxemia. However, the alpha-adrenergic system is not responsible for the hypoxemia-induced constriction of the renal vasculature.

Effects of ductus venosus obstruction on liver and regional blood flows in the fetal lamb.

The ductus venosus allows highly oxygenated blood returning from the umbilical-placental circulation to bypass the liver, and is believed thereby to facilitate preferential distribution of this blood to the fetal brain and heart. To examine this hypothesis, we developed a model that allows acute obstruction of the ductus venosus in chronically catheterized fetal lambs. In seven fetal lambs, a Swann-Ganz catheter was inserted into the inferior vena cava and the balloon tip advanced into the ductus venosus. Control measurements were obtained 1-2 d after surgery, before and during inflation of the balloon in the ductus venosus. At each sample time, radioactive microspheres were injected to determine organ blood flow and the distribution of umbilical venous blood flow. During balloon inflation, the percentage of umbilical venous return passing through the ductus venosus was reduced from 38 +/- 15% to 1 +/- 0.5%. Umbilical-placental blood flow was unchanged from control values of 181 +/- 33 mL/min/kg. Total liver blood flow increased from 346 +/- 98 to 553 +/- 105 mL/min/100 g. Pressure in the inferior vena cava did not change, but umbilical venous pressure increased from 7.2 +/- 2.7 to 8.7 +/- 3.5 mm Hg. Total vascular resistance across the liver and ductus venosus increased from 0.013 +/- 0.006 to 0.020 +/- 0.011 during ductus venosus obstruction. Fetal heart rate, arterial blood pressure, and descending aortic pH and blood gases were unchanged, as was oxygen content in the descending aorta and carotid artery. Organ blood flows, combined ventricular output, and oxygen delivery were also unchanged. In five animals, these studies were repeated during maternal hypoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)