Effects of indomethacin on cerebral blood flow and oxygen consumption in barbiturate-anesthetized Normocapnic and hypercapnic rats.
Although results obtained in baboons and rats have demonstrated that the fatty acid cyclo-oxygenase inhibitor indomethacin reduces cerebral blood flow (CBF) under control conditions and markedly attenuates the CBF response to hypercapnia, nonconfirmatory results have been obtained in rabbits and cats. Since these latter studies were carried out under barbiturate anesthesia, we tested the effect of indomethacin (10 mg kg-1) on CBF and cerebral oxygen consumption in rats anesthetized with 150 mg kg-1 of phenobarbital. At normocapnia the barbiturate reduced CBF, measured with a 133Xe modification of the Kety-Schmidt technique, to about 50% of nitrous oxide control values as previously determined with a similar technique. At this CBF level, indomethacin induced a small, albeit highly significant decrease in CBF. We suggest that a reduction of this magnitude will escape detection with some CBF techniques in current use. Indomethacin induced a highly significant decrease in CBF during hypercapnia, demonstrating that the barbiturate does not eliminate the effect of indomethacin on CO2 responsiveness. The magnitude of the reduction in CO2 response was so large that is should be detected with most methods for measuring CBF. A comparison with previous data on animals under 70% N2O demonstrated that phenobarbital reduced the CO2 responsiveness. defined as the ratio deltaCBF/deltaPCO2, to 39% of that observed under nitrous oxide analgesia. With both types of anesthesia, indomethacin curtailed the CO2 responsiveness 4- to 5-fold.
D000777:Anesthetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006935:Hypercapnia / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D009609:Nitrous Oxide; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D010634:Phenobarbital; D051381:Rats; D011919:Rats, Inbred Strains
D000777:Anesthetics; D009609:Nitrous Oxide; D010100:Oxygen; D007213:Indomethacin; D010634:Phenobarbital