EFFECTS OF INDOMETHACIN ON BRAIN BLOOD-FLOW, CEREBRAL METABOLISM, ANDSAGITTAL SINUS PROSTANOIDS AFTER HYPOXIA

We tested the hypotheses that during recovery from hypoxia, newborn pi glets exhibit a posthypoxic cerebral hyperemia, indomethacin-pretreate d piglets exhibit a posthypoxic cerebral hypoperfusion, and that the c hanges caused by indomethacin are dose dependent and related to the lo ss of prostanoids. We studied piglets exposed to 40 min of hypoxia aft er pretreatment with high (5 mg/kg, n = 9) or low (0.3 mg/kg, n = 8) d oses of indomethacin or placebo (n = 9) and allowed to recover for 120 min. In the placebo and low-dose pretreatment groups, total and regio nal brain blood flow increased during hypoxia but returned to baseline 10 min after hypoxia. High-dose indomethacin pretreatment was associa ted with a posthypoxic hypoperfusion to certain brain regions at 10 mi n of recovery to values similar to those after indomethacin treatment before the onset of hypoxia. During and after hypoxia, the cerebral me tabolic rate of oxygen was preserved in both the placebo and low-dose groups and decreased significantly during hypoxia in the high-dose gro up. Sagittal sinus prostacyclin was reduced significantly in both indo methacin-treated groups throughout the study. We conclude that a posth ypoxic hyperemia is not observed in newborn piglets. This finding was not altered by pretreatment with a therapeutic dose of indomethacin, w hereas a pharmacological dose was associated with selective hypoperfus ion to certain brain regions both before hypoxia and during recovery f rom hypoxia.