Pharmacological, hematological, and physiological effects of a new thromboxane synthetase inhibitor (CGS-13080) during cardiopulmonary bypass in dogs

Abstract

The hematological and pharmacological effects of a new thromboxane synthetase inhibitor, CGS-13080 (imidazo[1,5-α]pyridine-5-hexanoic acid), were investigated during cardiopulmonary bypass in a blinded, randomized manner in dogs. Compared with placebo, CGS-13080 suppressed thrombin-stimulated platelet thramboxane B 2 production by 90% during cardfopulmonary bypass ( p <.001), an effect that persisted for two hours after stopping the infusion. In the CGS-13080-treated group, plasma 6-keto-prostaglandin F 1α levels significantly increased over time ( p <.03) and were somewhat higher when compared with those in the placebo-treated group. This observation suggests that an “endoperoxide shunt” may have occurred. In the control group, an inverse correlation between platelet count and level of thromboxane B 2 per platelet following in vitro thrombin stimulation ( r = .5, p <.001) was apparent, but there was no correlation between these two variables ( r = .18, p >.10) in the CGS-13080-treated group. No adverse hemodynamic or other effects attributable to CGS-13080 occurred during or immediately following cardiopulmonary bypass. These results suggest that CGS-13080 is an effective inhibitor of thromboxane B 2 production during cardiopulmonary bypass in dogs and has no adverse physiological effects.