THROMBOXANE ANTAGONISM IN EXPERIMENTAL CANINE CAROTID-ARTERY THROMBOSIS

Background and Purpose: The two objectives of this study were to asses s the potential of BAY U 3405 to prevent arterial thrombosis in respon se to vessel wall injury and to determine the ability of BAY U 3405 to prevent thrombotic reocclusion after thrombolysis with anisoylated pl asminogen streptokinase activator complex. Methods: Dogs were instrume nted with a carotid flow probe, stimulating electrode, and a stenosis. Current (150 muA) was applied to the intimal surface of the right car otid artery, and time to occlusive thrombus formation was noted. BAY U 3405 was administered, and the procedure for thrombus formation was r epeated for the left carotid artery. Results: BAY U 3405 administratio n prevented occlusive arterial thrombosis formation. Ex vivo platelet aggregation was inhibited, bleeding time increased, and thrombus weigh t reduced after BAY U 3405 treatment. In a second group, thrombi were formed initially in both carotid arteries, BAY U 3405 was administered as before, and anisoylated plasminogen streptokinase activator comple x was infused in the right carotid artery proximal to the occlusive th rombus. BAY U 3405 did not after the incidence of rethrombosis compare d with the lytic agent alone. Conclusions: BAY U 3405 prevented primar y arterial thrombosis, corresponding to inhibition of platelet aggrega tion, and increased bleeding times. BAY U 3405, however, did not preve nt rethrombosis after successful thrombolysis with anisoylated plasmin ogen streptokinase activator complex, despite the fact that platelet r eactivity was inhibited. The data are consistent with the concept that the residual thrombus represents a more effective thrombogenic stimul us as compared with arterial wall injury alone and that the mechanisms associated with primary versus secondary thrombus formation may requi re separate therapeutic approaches.