PROSTAGLANDIN-I2 AND INDOMETHACIN PREVENT IMPAIRMENT OF POST-ISCHEMIC BRAIN REPERFUSION IN THE DOG

Twenty-seven heparinized dogs were exposed to 35 min of cerebrospinal fluid compression ischemia followed by 30 min of recirculation. The degree and distribution of post-ischemic reperfusion was then assessed by means of a 14C-antipyrine autoradiographic blood flow study. The animals were assigned to 5 groups by the administration of drugs as follows; 1) no additional drugs; 2) indomethacin 1.5 or 4 mg/kg prior to ischemia; 3) indomethacin 4 mg/kg 5 min after ischemia; 4) prostaglandin I2 (PGI2) infusion 30-180 ng/kg/min beginning 5 min after ischemia; and 5) indomethacin 4 mg/kg 5 min after ischemia plus PG12 infusion 30-130 ng/kg/min beginning 5 min after ischemia. Animals receiving no additional drugs had relatively low post-ischemic blood flows with focal zones of greatly impaired reperfusion. Animals receiving either indomethacin or PG12 after ischemia did not differ significantly from the no additional drug group. A significant enhancement of post-ischemic reperfusion occurred in animals receiving indamethacin prior to ischemia and those receiving the combination of indamethacin and PGI2 after ischemia. These observations implicate an imbalance in prostaglandin pathways at the blood-endothelial interface in the genesis of post-ischemic reflow impairment and suggest novel drug therapy for enhancing nutrient flow after ischemia. © 1979 American Heart Association, Inc.