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Ann Thorac Surg 1986;42:690-696
© 1986 The Society of Thoracic Surgeons

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Articles

Pharmacological, Hematological, and Physiological Effects of a New Thromboxane Synthetase Inhibitor (CGS-13080) During Cardiopulmonary Bypass in Dogs

From the Department of Cardiovascular Surgery, the Department of Radiology, Division of Nuclear Medicine, and the Department of Pathology, Stanford University Medical School, and the Cardiac Surgery Section, Palo Alto VA Medical Center, Stanford, CA

Accepted for publication February 10, 1986.

^* Address reprint requests to Dr. Miller, Department of Cardiovascular Surgery, Cardiovascular Research Center, Stanford University Medical Center, Stanford, CA 94305

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 thromboxane B₂ production by 90% during cardiopulmonary 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 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.

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