AH23848, a thromboxane antagonist, suppresses ischaemia and reperfusion-induced arrhythmias in anaesthetized greyhounds.

The effects of the thromboxane antagonist AH23848 (1 mg kg-1 i.v.) were examined in anaesthetized greyhounds prepared for occlusion of the left anterior descending coronary artery with subsequent reperfusion after 40 min of myocardial ischaemia. Pretreatment with AH23848 30 min before coronary artery occlusion reduced the number of ischaemia-induced extrasystoles to 339 +/- 111 compared with 736 +/- 153 in the control group. The incidence of ventricular fibrillation following reperfusion was also markedly reduced; 25% compared with 88% in the controls. Late intervention with AH23848, 25 min after the onset of myocardial ischaemia did not significantly alter the incidence of reperfusion-induced ventricular fibrillation; 70% of the control group died and 60% of those that received AH23848. The ischaemia-induced release of thromboxane A2 and prostacyclin was not altered by pretreatment with AH23848. The results suggest that blockade of thromboxane receptors before myocardial ischaemia is an effective antiarrhythmic strategy in this model.