Effect of thromboxane synthetase inhibition on vulnerability to ventricular arrhythmia following coronary occlusion

Release of thromboxane (TXA2) during acute myocardial infarction may be an important contributing factor in the genesis of ventricular fibrillation (VF). We assessed the effect of selective TXA2 inhibition on vulnerability to VF after total occlusion of the anterior descending coronary artery in chloralose-anesthetized cats. Animals were pretreated with vehicle or with CGS-13080, a TXA2 synthetase inhibitor, 3.0 or 9.0 mg/kg intravenously. There was an apparent dose-dependent protective effect following CGS-13080 administration, in which the decrease in VF threshold following coronary occlusion was attenuated. Also, the incidence of spontaneous ventricular arrhythmia in the first 30 minutes after occlusion was reduced by two thirds in the 9.0 mg/kg CGS-13080 group compared to the vehicle-treated animals. This protective effect does not appear to be due to a change in hemodynamics, effective refractory periods, or extent of ischemia. TXA2 released during coronary occlusion appears to be arrhythmogenic, and inhibiting its synthesis may be protective.