ENDOTHELIN-1 PRODUCTION IN CORONARY CIRCULATION IN A NEW CANINE MODELOF CORONARY-THROMBOSIS

Objective: The purpose of this study was to investigate whether endoge nous endothelin-l (ET-1) production in coronary circulation is associa ted with acute coronary thrombotic events in vivo. To achieve this goa l, we have designed a new experimental canine model of coronary thromb osis. Methods: In vivo occlusive thrombus was induced by the intracoro nary application of radiofrequency energy (660 kHz, 50 W) in closed-ch est dogs. Pathological and immunohistochemical examinations of thrombo sed coronary artery were performed. In 12 dogs, plasminogen activator was administered intravenously and serial measurements of ET-1, thromb oxane B-2 (TXB(2)) and thrombin-antithrombin III complex (TAT) levels in plasma from the coronary sinus, aortic root and inferior vena cava were examined. Results: Occlusive platelet-rich thrombi were attached to the deeply injured intimal surface. TAT and TXB(2) increased rapidl y soon after the intimal injury and declined after successful thrombol ysis. In contrast, ET-I in the coronary sinus was elevated after reper fusion and was significantly higher than in the aorta. Net ET-1 produc tion in the coronary circulation showed a significant positive correla tion with the peak TAT levels (r = 0.69, P < 0.05), but not with TXB(2 ) or total occlusion time as an index of ischemic severity, Conclusion s: Deep intimal injury leads to occlusive coronary thrombus. Thrombus formation and its subsequent lysis is associated with the activation a nd deactivation, respectively, of the coagulation cascade and platelet s. Thrombin generation may stimulate ET-I production in the coronary e ndothelium in acute coronary thrombotic events.