Effects of Indomethacin on Cerebral Blood Flow and Oxygen Consumption in Barbiturate-Anesthetized Normocapnic and Hypercapnic Rats

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Abstract
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−1of phenobarbital. At normocapnia the barbiturate reduced CBF, measured with a133Xe 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 CO2responsiveness. The magnitude of the reduction in CO2response was so large that it should be detected with most methods for measuring CBF. A comparison with previous data on animals under 70% N2O demonstrated that phenobarbital reduced the CO2responsiveness, defined as the ratio ΔCBF/ΔPco2, to 39% of that observed under nitrous oxide analgesia. With both types of anesthesia, indomethacin curtailed the CO2responsiveness 4- to 5-fold.