Effect of Bay U 3405, a new thromboxane antagonist, on collagen-induced thromboembolism in rabbits

Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid] potently inhibits platelet aggregation, thromboxane A2-induced contraction of smooth muscles, and coronary artery thrombosis. We have previously demonstrated inhibition of arachidonic acid-induced sudden death by Bay U 3405. The purpose of this study was to investigate the effects of Bay U 3405 on thromboembolism provoked by collagen. Collagen fibrils dissolved in an isotonic glucose solution were injected into a marginal ear vein of anesthetized rabbits. Sudden death occurred within a few minutes due to elevated thromboxane A2 levels causing intravascular platelet aggregation and myocardial ischemia. In the vehicle-treated group, 100% of the animals died. One of the most prominent parameters was the massive fall in blood pressure. All animals pretreated with 10 mg/kg orally Bay U 3405 survived, showing only a transient hypotensive effect. Tracings of the electrocardiogram and heart rate were unchanged. Bay U 3405 will therefore be useful to elucidate the role of thromboxane A2 in various cardiovascular and respiratory diseases.