EFFECT OF AN ENDOTHELIN-1 ANTAGONIST, BQ-485, ON CEREBRAL OXYGEN-METABOLISM AFTER COMPLETE GLOBAL CEREBRAL-ISCHEMIA IN DOGS

Endothelin-1 (ET-1) plays an important role in the physiologic or path ophysiologic regulation of cerebral circulation. To evaluate the effec ts of the newly synthesized ET(A) receptor-selective antagonist, BQ-48 5 N-perhydroazepin-1-ylcarbonyl-Leu-D-Trp-D-Trp-OH), on the cerebral m etabolism of oxygen during the delayed cerebral hypoperfusion that fol lows global cerebral ischemia, we occluded the ascending aorta and cav al veins of 10 beagle dogs for 12.5 min. The animals were randomized i nto two groups. BQ-485 was given directly into the carotid artery at 0 .03 mg/kg per min for 30 min, starting 15 min after reperfusion in the treatment group (n = 5). Isotonic saline was infused in the control g roup (n = 5). A fiberoptic catheter was inserted into the superior sag ittal sinus to monitor its oxygen saturation (S-ssO2) continuously. Ar terial O-2 content (Ca-o2): and sagittal sinus O-2 content (C-ssO2) we re monitored before and at 0.5, 1, 2, 4, 6 and 8 h after the ischemic insult. BQ-4X5 significantly prevented the expected decrease in S-SSO2 and increase in the cerebral O-2 utilization coefficient at 4, 6 and 8 h after the ischemic insult (P < 0.05). Thus, BQ-485 ameliorated the mismatch between O-2 supply and demand in the delayed hypoperfusion p hase. We conclude that ET may be involved in the pathogenesis of delay ed cerebral hypoperfusion after cardiac arrest. (C) 1997 Elsevier Scie nce Ireland Ltd.