Effects of indomethacin on brain blood flow, cerebral metabolism, and sagittal sinus prostanoids after hypoxia

Abstract

We tested the hypotheses that during recovery from hypoxia, newborn piglets exhibit a posthypoxic cerebral hyperemia, indomethacin-pretreated piglets exhibit a posthypoxic cerebral hypoperfusion, and that the changes caused by indomethacin are dose dependent and related to the loss of prostanoids. We studied piglets exposed to 40 min of hypoxia after pretreatment with high (5 mg/kg, n = 9) or low (0.3 mg/kg, n = 8) doses of indomethacin or placebo (n = 9) and allowed to recover for 120 min. In the placebo and low-dose pretreatment groups, total and regional brain blood flow increased during hypoxia but returned to baseline 10 min after hypoxia. High-dose indomethacin pretreatment was associated with a posthypoxic hypoperfusion to certain brain regions at 10 min of recovery to values similar to those after indomethacin treatment before the onset of hypoxia. During and after hypoxia, the cerebral metabolic rate of oxygen was preserved in both the placebo and low-dose groups and decreased significantly during hypoxia in the high-dose group. Sagittal sinus prostacyclin was reduced significantly in both indomethacin-treated groups throughout the study. We conclude that a posthypoxic hyperemia is not observed in newborn piglets. This finding was not altered by pretreatment with a therapeutic dose of indomethacin, whereas a pharmacological dose was associated with selective hypoperfusion to certain brain regions both before hypoxia and during recovery from hypoxia.