PROSTAGLANDIN-MEDIATED CONTROL OF NEONATAL CEREBRAL BLOOD FLOW

Abstract

Intraventricular hemorrhage (IVH) represents a major problem of preterm neonates & is believed to be secondary to alterations in cerebral blood flow (CBF). The newborn beagle pup provides an excellent model for the study of this problem as well as for the study of neonatal CBF. We have studied the alterations in CBF in the newborn beagle pup exposed to hemorrhagic hypotension followed by volume re-expansion for IVH & the effects of the PG-system inhibitors, indomethacin (INDO), ethamsylate (ETHAM) & superoxide dismutase (SOD) in this model system. INDO, believed to inhibit the cyclo-oxygenase pathway, prevented IVH (8% incidence), blunted the BP changes found in saline pretreated pups (IVH rate 75%) & prevented the cortical & germinal matrix CBF changes found in that group as well. ETHAM thought to inhibit the PG-specific synthetic enzymes, lowered baseline CBF, but prevented IVH less well than INDO (30%). ETHAM only somewhat blunted CBF changes & did not prevent the BP changes found in this model. SOD, a free-radical scavenger, prevented IVH (10%) but had no effect on CBF or BP. INDO & ETHAM inhibited the synthesis of TXB2 & 6-keto PGF1α, the breakdown products of TXA2 & PGI2 respectively (baseline controls: TXB2 700 pg/ml, 6-keto PGF1α 650 pg/ml; after INDO 289, 250 respectively; after ETHAM 132, 247 respectively). SOD had no effect on the synthesis of either PG. We hypothesize that neonatal IVH may be secondary to both alterations in CBF & free radical mediated germinal matrix capillary changes.