The effect of the inhibition of prostaglandin synthesis on renal blood flow in fetal sheep.

Treatment with prostaglandin synthesis inhibitors has been associated with oligohydramnios in the fetus. The presumed mechanism is a reduction in fetal renal blood flow. We examined the effect of meclofenamate administration on renal blood flow in chronically catheterized fetal sheep during normoxia and during moderate and severe hypoxia. Ten fetal sheep were made hypoxic twice at least 4 days after surgery: once in the presence and once in the absence of meclofenamate infusion. Renal blood flow and combined ventricular output were measured with radioactive microspheres. Prostaglandin synthesis blockade with meclofenamate caused no significant change in blood pressure, combined ventricular output, renal blood flow, or renal vascular resistance in either the normoxic or hypoxic animals. These data challenge the contention that prostaglandin activity protects the renal vascular bed of the fetus from vasoconstriction during hypoxia and they also do not support the hypothesis that prostaglandin synthesis inhibition causes oligohydramnios through reduction of fetal renal blood flow.

Cerebral oxygen consumption during asphyxia in fetal sheep.

Cerebral blood flow and cerebral arteriovenous oxygen content difference were measured in 17 fetal sheep, and cerebral oxygen uptake was calculated. The measurements were made under control conditions and after profound fetal asphyxia induced of uterine blood flow for up to 90 min. In 14 of the fetal sheep, sequential measurements were made to examine hemodynamic changes and cerebral oxygen consumption at comparable intervals up to 36 min of asphyxia. These fetuses initially had elevated blood pressure and lowered heart rate became hypoxemic, hypercarbic, and acidotic. There was an initial decrease in cerebral oxygen consumption. Sequential measurements, however, showed a relative stability in this decreased oxygenation during 4 to 36 min of asphyxia despite a progressive metabolic acidosis. The cerebral fractional oxygen extraction remained unchanged despite a mean pH of 6.98 at 36 min. The calculated cerebral oxygen uptake during asphyxia in all 17 sheep was grouped according to whether the ascending aortic oxygen content was greater or less than 1.0 mmol/l. In the first group with mean ascending aortic oxygen content of 1.3 mmol/l, blood flow to the brain was increased and cerebral oxygen consumption was 85% of control. In the second group with mean arterial blood oxygen content of 0.8 mmol/l, there was a narrowing of the arteriovenous oxygen content difference, but no further increase in cerebral blood flow. Cerebral oxygen consumption was only 48% of control in this more asphyxiated group. We conclude that the degree of hypoxemia in the second group represents a point where physiologic mechanisms cannot compensate, and may be associated with neuronal damage.