THROMBOXANE RECEPTOR ANTAGONIST BMS-180291, BUT NOT ASPIRIN, REDUCES THE SEVERITY OF PACING-INDUCED ISCHEMIA IN DOGS

We determined the effect of thromboxane A(2) (TXA(2)) prostaglandin en doperoxide (TP) receptor antagonism, using BMS-180291 or aspirin, on t he severity of pacing-induced ischemia in anesthetized dogs. Thromboxa ne receptor antagonists may not only have antithrombotic activity, but may also have direct cardioprotective effects, unlike aspirin. Left a nterior descending coronary artery (LAD) stenosis was adjusted so that a significant (10-12 mV) ST segment elevation was observed only when superimposed on atrial pacing. Each heart was subjected to 5-min episo des of pacing-induced ischemia 10, 40, and 70 min after initiation of BMS-180291 (1 mg/kg + 1 mg/kg/h) or vehicle. In the vehicle group, ST segment elevation was reproducible at all pacing-induced ischemia epis odes, whereas BMS-180291 significantly reduced it by 30% at the later ischemia episodes. This reduction in ST segment increase was not accom panied by alterations in regional myocardial blood flow (RMBF) nor in hemodynamic status. Aspirin in the same model [10 mg/kg intravenously (i.v.) given 10 min before pacing-induced ischemia] did not significan tly reduce ST segment elevation, indicating a lack of protective effec t in this model. Thromboxane receptor blockade appears to protect myoc ardium subjected to pacing-induced ischemia, an effect not produced by aspirin.