Evidence that thromboxane contributes to ventricular fibrillation induced by reperfusion of the ischaemic myocardium

In many victims of sudden cardiac death, resulting from ventricular fibrillation, there is no post-mortem evidence of coronary thrombosis [ 7] and it is thought that spasm of the coronary arteries or reversal of such spasm may be the cause of the ventricular fibrillation. When coronary vasospasm is reversed, either spontaneously or by other means, arrhythmias are frequently observed when perfusion of the formerly ischaemic area of the myocardium is restored. These “reperfusion arrhythmias” are particularly severe and frequently fatal since they often progress to ventricular fibrillation. They also appear to be resistant to standard antiarrhythmic therapy [ 5] suggesting that their aetiology may vary from that of arrhythmias observed during myocardial ischaemia. We have reported previously [ 3] that thromboxane A 2, a potent vasoconstrictor which promotes platelet aggregation, is released during acute myocardial ischaemia and that this release is related to the occurrence of early cardiac arrhythmias. In the present study we have extended our experiments in anaesthetized greyhounds to investigate whether thromboxane plays a role in the reperfusion arrhythmias that occur following the release of a 40 min coronary artery occlusion. Dazoxiben (UK-37, 248), a selective thromboxane synthetase inhibitor [ 6], markedly increased survival following coronary artery reperfusion suggesting that thromboxane is an important contributory factor in post-reperfusion ventricular fibrillation.