Thromboxane antagonism in experimental canine carotid artery thrombosis.
OBJECTIVE
The two objectives of this study were to assess the potential of BAY U 3405 to prevent arterial thrombosis in response to vessel wall injury and to determine the ability of BAY U 3405 to prevent thrombotic reocclusion after thrombolysis with anisoylated plasminogen streptokinase activator complex.


METHODS
Dogs were instrumented with a carotid flow probe, stimulating electrode, and a stenosis. Current (150 microA) was applied to the intimal surface of the right carotid artery, and time to occlusive thrombus formation was noted. BAY U 3405 was administered, and the procedure for thrombus formation was repeated for the left carotid artery.


RESULTS
BAY U 3405 administration prevented occlusive arterial thrombosis formation. Ex vivo platelet aggregation was inhibited, bleeding time increased, and thrombus weight 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 complex was infused in the right carotid artery proximal to the occlusive thrombus. BAY U 3405 did not alter the incidence of rethrombosis compared with the lytic agent alone.


CONCLUSIONS
BAY U 3405 prevented primary arterial thrombosis, corresponding to inhibition of platelet aggregation, and increased bleeding times. BAY U 3405, however, did not prevent rethrombosis after successful thrombolysis with anisoylated plasminogen streptokinase activator complex, despite the fact that platelet reactivity was inhibited. The data are consistent with the concept that the residual thrombus represents a more effective thrombogenic stimulus as compared with arterial wall injury alone and that the mechanisms associated with primary versus secondary thrombus formation may require separate therapeutic approaches.
Rote
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Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
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Lucchesi
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D000818:Animals; D002227:Carbazoles / Q000627:therapeutic use*; D002341:Carotid Artery Thrombosis / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D013449:Sulfonamides / Q000627:therapeutic use*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D002227:Carbazoles; D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D013928:Thromboxane A2; C063119:ramatroban