Prostaglandin Inhibition and Cerebrovascular Hemodynamics in Normal and Ischemic Human Brain

Abstract

Indomethacin is a potent inhibitor of prostaglandin synthesis. Indomethacin effects on cerebral blood flow (CBF) in normal subjects and patients with ischemic cerebrovascular disease were measured by133Xe inhalation method and compared. Thirteen normal subjects with muscle contraction headaches were tested and compared to three groups of patients with ischemic cerebrovascular disease: (1) a transient ischemic attack (TIA) group, consisting of 8 patients, (2) a recent cerebral infarction group consisting of 10 patients with recent stroke (within 2 months), and (3) a chronic cerebral infarction group, consisting of 10 patients with remote stroke (exceeding 2 months). From the three groups, 7 patients with internal carotid artery occlusion also underwent superficial temporal artery to middle cerebral artery (STA-MCA) bypass; this group was tested before and after the operative procedure. Indomethacin induced significant CBF reductions in the TIA and chronic cerebral infarction groups but there were no significant effects in the recent cerebral infarction group and many showed paradoxical increases. Plotting indomethacin-induced CBF changes according to the time course of cerebral infarction indicated that abnormal responses gradually returned toward normal within 16 weeks. Indomethacin-induced CBF changes were measured prospectively in patients undergoing STA-MCA bypass. Indomethacin had no significant effect on CBF before the procedure, but significantly reduced CBF (i.e., mean CBF became reduced) after surgery. Comparison of the time course for recovery of indomethacin-induced CBF responses in non-operated cases indicated that the post-operative difference in response could be due to the natural history of the disease rather than to surgery. Present studies confirm that prostaglandins play an important part in cerebral vascular control in man, and that these agents are temporarily deranged following acute cerebral infarction, which may account for temporary alterations in regional cerebrovascular responsiveness to 5% CO2and 100% O2inhalation after stroke.