AS ORIGINALLY PUBLISHED IN 1986 - PHARMACOLOGICAL, HEMATOLOGICAL, ANDPHYSIOLOGICAL-EFFECTS OF A NEW THROMBOXANE SYNTHETASE INHIBITOR (CGS-13080) DURING CARDIOPULMONARY BYPASS IN DOGS (REPRINTED FROM ANN-THORAC-SURG, VOL 42, PG 690-6, 1986)

The hematological and pharmacological effects of a new thromboxane syn thetase inhibitor, CGS-13080 (imidazo[1,5-alpha]pyridine-5-hexanoic ac id), were investigated during cardiopulmonary bypass in a blinded, ran domized manner in dogs. Compared with placebo, CGS-13080 suppressed th rombin-stimulated platelet thromboxane B-2 production by 90% during ca rdiopulmonary bypass (p < .001), an effect that persisted for two hour s after stopping the infusion. In the CGS-13080-treated group, plasma 6-keto-prostaglandin F-1 alpha, levels significantly increased over ti me (p < .03) and were somewhat higher when compared with those in the placebo-treated group. This observation suggests that an ''endoperoxid e shunt'' may have occurred. In the control group, an inverse correlat ion between platelet count and level of thromboxane B-2 per platelet f ollowing 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-1308O-treated group. No adverse hemodynamic or othe r effects attributable to CGS-13080 occurred during or immediately fol lowing cardiopulmonary bypass. These results suggest that CGS-13080 is an effective inhibitor of thromboxane B-2 production during cardiopul monary bypass in dogs and has no adverse physiological effects.