Eicosanoids and susceptibility to ventricular arrhythmias during myocardial ischaemia and reperfusion

Increased levels of the major metabolites of thromboxane (TxA2) and prostacyclin (PGI2) are found in venous blood draining the ischaemic region of the myocardium of dogs subjected to acute coronary artery occlusion. This suggests that these arachidonic acid derivatives are released under conditions of myocardial ischaemia and may be considered as mediators of some of the consequences of coronary blood flow reduction, including arrhythmogenesis. The present experimental evidence suggests that thromboxane release is detrimental both in the early stages of ischaemia and in reperfusion since the severity of both ischaemia and reperfusion-induced arrhythmias is reduced by selective inhibition of thromboxane synthesis or by thromboxane receptor blockade. Since the local administration of prostacyclin (or iloprost) or the promotion of local prostacyclin production (with nafazatrom) reduces the severity of ischaemia and reperfusion-induced arrhythmias, it is suggested that prostacyclin may act as a local, endogenous antiarrhythmic agent. The conclusion thus far from these experimental studies suggests that the prostacyclin-thromboxane balance is one important factor involved in determining the severity of ischaemia and reperfusion-induced arrhythmias but that the mechanisms have not as yet been clearly defined.