Effect of the cyclo-oxygenase blocker ibuprofen on cerebral blood volume and cerebral blood flow during normocarbia and hypercarbia in newborn piglets

Abstract

Indomethacin modifies baseline cerebral haemodynamics and metabolism, as well as vasomotor adaptive responses. However, the significance of arachidonic acid metabolites in the regulation of cerebral circulation remains unclear. A study was made of the effect of inhibition of the cyclo-oxygenase pathway on baseline cerebral haemodynamics and CO2-induced vasodilation using the more specific cyclo-oxygenase blocker ibuprofen in a neonatal pig model. Two methods were used: radiolabelled microspheres to measure cerebral blood flow and near infrared spectroscopy to calculate absolute changes in cerebral blood volume. The relationship between CO2-induced changes in these two haemodynamic parameters was evaluated. Fifteen newborn piglets <7 d old received an i.v. infusion of either ibuprofen (30 mg/kg) (IB group, n = 8) or saline (control group, n = 7). Cerebral blood flow and absolute changes in cerebral blood volume were measured while the piglets were breathing room air at baseline and 30 min after infusion of ibuprofen or saline, and 15 min and 30 min after inducing hypercarbia. Global and regional cerebral blood flow (ml/hg/min) and absolute changes in cerebral blood volume (ml/hg) did not vary between baseline and 30 min after infusion of ibuprofen or saline. During hypercarbia, global and regional cerebral blood flow and absolute changes in cerebral blood volume increased significantly in both the ibuprofen and control groups (p < 0.01). The mean percentage increases in blood flow and blood volume at each measurement were almost identical, with approximately 90% of the increase in both parameters occurring after 15 min of hypercarbia, then reaching a plateau. However, we found no agreement between cerebral blood flow changes and absolute changes in cerebral blood volume. We conclude that ibuprofen did not alter either baseline cerebral circulation or physiological CO2-induced vasodilation in newborn pigs. We speculate that hypercarbic cerebral vasodilation could be caused either by mediators other than the cyclo-oxygenase metabolites of arachidonic acid or by a direct effect on vessel walls.