The Effects of Treatment with Indomethacin on the Cerebral Vasculature of Newborn Piglets before and during Hemorrhagic Hypotension

Substantial physiologic data point to a significant role for dilator prostanoids in the regulation of cerebral vascular tone in newborn pigs. This study begins to address the hypothesis that multiple dilator systems, including prostanoids, can provide for the initiation and maintenance of cerebral vasodilatation in response to hypotension. Piglets were anesthetized, and cranial windows were implanted. Hypotension was achieved by hemorrhage to 50% of the control arterial pressure and maintained for 10 min. Each piglet served as its own control by the induction of hypotension and return to normotension before treatment. Pial arterioles dilated (38 ± 5% increase in diameter) in response to hypotension. Pretreatment with indomethacin (5 mg/kg i.v.) at 20 min and immediately before hypotension did not block this response (28 ± 7% and 23 ± 9% increase in diameter, respectively). In contrast, when indomethacin was administered 10 min into the hypotensive period, the dilated arterioles (106 ± 6 μm) constricted to the normotensive diameter (75 ± 5 μm) and remained constricted for the duration of the observation. These findings suggest that compensatory mechanisms provide for cerebral vasodilation when prostanoid synthesis and prostacyclin receptors are blocked before hemorrhagic hypotension. However, removal of prostanoids after vasodilation is established in response to hypotension causes constriction without compensation from alternative mechanisms. Awareness of these findings may be important when considering giving indomethacin to sick preterm infants during periods of cardiac instability.