EFFECTS OF INDOMETHACIN ON BRAIN BLOOD-FLOW AND CEREBRAL METABOLISM IN HYPOXIC NEWBORN PIGLETS

We tested hypotheses that in newborn piglets indomethacin (In ) pretreatment blunts the hyperemic brain blood flow (BF) and alters the cerebral metabolic responses to hypoxia and that these responses are dose dependent. We studied 23 chronically instrumented piglets exposed to graded hypoxia (O2 content: 7.1-0.4 muM O2/Ml) after pretreatment with high (5 mg/kg, n = 8)- or low (0.3 mg/kg, n = 6)-dose Indo or placebo (diluent, n = 9). Total and regional brain BF increased significantly with decreasing 02 content values (P < 0.01) in all three groups. However, the rise in the brain BF curves with decreasing 02 content values was significantly (P < 0.05) lower in the high- compared with the low-dose group in all brain regions with the greatest effect in the caudal regions. Furthermore, the BF curves in the placebo-treated animals were similar to the low-dose group. The cerebral metabolic rate Of O2 (CMR(O2)) and glucose metabolism were preserved in the three groups over all hypoxic ranges until severe hypoxia (O2 content less-than-or-equal-to 1.1 muM O2/Ml) was achieved in the high-dose group, when CMR(O2), decreased (P < 0.05), and glucose metabolism increased (P < 0.05). The mean arterial blood pressure in the high-dose group during severe hypoxia was 45 mmHg (P > 0.05). Although coupling of cerebral BF and CMR(O2), was preserved in the three groups, this association was significantly altered with high-dose pretreatment. We conclude that an attenuation in the hypoxia-induced brain perfusion by Indo is dose dependent. Alterations in CMR(O2), and glucose metabolism are observed with high-dose pretreatment during severe hypoxia, and the responses to hypoxia are similar with placebo and low-dose Indo pretreatment.