Treatment of unanesthetized newborn pigs with indomethacin trihydrate (5 +/- 1 mg/kg, intravenous) decreased cerebral blood flow uniformly throughout the brain by 18-28% without changing cardiac output, arterial pressure, or arterial blood gases and pH. Breathing 10% O2, 9% CO2 with the balance N2 (hypoxia/hypercapnia) caused cerebral blood flow to increase from 102 +/- 12 to 218 +/- 19 ml/100 g . min. Intravenous administration of indomethacin during hypoxia/hypercapnia caused a uniform decrease in cerebral flow throughout the brain to levels (94 +/- 5 ml/100 g . min) indistinguishable from those when the piglet was breathing ambient air. Further, 2.5 h later, the cerebral hyperemia caused by hypoxia/hypercapnia was attenuated markedly (129 +/- 19 ml/100 g . min). Vehicle treatment did not alter resting cerebral blood flow or cerebral hyperemia in response to hypoxia/hypercapnia. Measurements of 6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 demonstrated that intravenously administered indomethacin crossed the blood-brain barrier of newborn pigs in sufficient quantity to inhibit prostanoid release into the cerebrospinal fluid passing over the surface of the brain. The mechanism by which indomethacin reduces cerebral blood flow and attenuates cerebral hyperemia cannot be determined from the present experiments. We conclude that intravenous administration of indomethacin decreases cerebral blood flow and attenuates cerebral hyperemia induced by severe, combined hypoxia/hypercapnia in newborn pigs.

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Products of reactions catalyzed by prostaglandin cyclo-oxygenase [prostaglandins (PG), thromboxanes] were analyzed by gas chromatography with electron-capture detection in the venous effluents of in situ Krebs-perfused lungs of exteriorized fetal goats and sheep before and after ventilation with air. The major products were 6-keto-PGF1 alpha and 6,15-diketo[13,14-dihydro] PGI2 without blood components. After ventilation, which decreased pulmonary vascular resistance to 63% of the before-ventilation value, lung production of 6-keto-PGF1 alpha and metabolite increased 50 and 230%, respectively. These data, in addition to earlier findings of inhibition of ventilation-induced pulmonary vasodilation by indomethacin and increased net production of PG-like material after ventilation of blood-perfused fetal lungs, support the hypothesis that ventilation of fetal lungs with air at birth increases synthesis of PGI2 by or near pulmonary resistance vessels, resulting in high local concentrations of PGI2 near its site of production. PGI2 appears to be important in the pulmonary vascular resistance decrease that is necessary for successful perinatal transition.