Effects of indomethacin upon cerebral hemodynamics of newborn pigs.
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.
D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006935:Hypercapnia / Q000503:physiopathology; D006940:Hyperemia / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007213:Indomethacin / Q000378:metabolism / Q000494:pharmacology*; D011453:Prostaglandins / Q000097:blood / Q000134:cerebrospinal fluid; D013552:Swine
D011453:Prostaglandins; D007213:Indomethacin