Indomethacin attenuates the cerebral blood flow response to hypotension inlate-gestation fetal sheep

Previous studies by us and others have demonstrated that PGE(2) and thrombo xane (Tx) B-2 are produced in the fetal and neonatal brain during cerebral hypoperfusion. The present study was to test the hypotheses that indomethac in would alter the cerebral blood flow (CBF) response to reduced cerebral p erfusion pressure in late-gestation fetal sheep by inhibiting the local pro stanoid production. We studied eight chronically catheterized, sinoaortical ly denervated, 126- to 136-day gestation fetal sheep. The cyclooxygenase in hibitor indomethacin (0.2 mg/kg) or its vehicle phosphate buffer was inject ed intravenously 90 min before the start of a 10-min period of cerebral hyp operfusion produced by brachiocephalic artery occlusion (BCO). We found tha t BCO decreased fetal regional CBF (rCBF) by 65-79% in the phosphate buffer group and by 45-57% in the indomethacin-pretreated group. The decrease in fetal rCBF during BCO after indomethacin was 30-49% less than after phospha te buffer. Plasma PGE(2) and TxB(2) concentrations were significantly reduc ed by indomethacin treatment. BCO increased plasma ACTH and arginine vasopr essin (AVP) concentrations; but these responses were not affected by indome thacin. These data suggested that endogenous prostanoid production is invol ved in the regulation of fetal CBF but, in the absence of intact baro- or c hemoreflexes, not in the regulation of ACTH or AVP responses to BCO. We con clude that indomethacin has a beneficial effect on CBF during cerebral isch emia in late-gestation fetal sheep.