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 B2 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 F1α 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 B2 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 B2 production during cardiopulmonary bypass in dogs and has no adverse physiological effects.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cardiology and Cardiovascular Medicine