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

William M. DeCampli, David Goodwin, Jon C. Kosek, Cynthia E. Handen, R. Scott Mitchell, D. Craig Miller, Abe DeAnda

Research output: Contribution to journalArticle

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 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 F 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.

Original languageEnglish (US)
Pages (from-to)778-780
Number of pages3
JournalThe Annals of Thoracic Surgery
Volume57
Issue number3
DOIs
StatePublished - Mar 1994
Externally publishedYes

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ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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