Study objective: The aim was to evaluate the arrhythmogenic effect of a free radical generating system, FeCl3/ADP using two different approaches.
Design: Ventricular arrhythmias were studied in isolated rat hearts subjected to regional ischaemia and reperfusion without or with simultaneous treatment with nicergoline (0.4 mg.litre-1). In the second part of this study the electrophysiological effects of FeCl3/ADP (0.1/1.0 microM) were investigated in normal Purkinje fibres and in Purkinje fibres from dog surviving infarction, by using conventional microelectrode method.
Experimental materials: Hearts were obtained from male Sprague-Dawley rats, weight 250-300 g. Purkinje fibres were dissected from hearts of mongrel dogs of either sex (10-15 kg) with or without prior myocardial infarction.
Measurements and results: FeCl3/ADP (0.1/1.0 microM and 1.0/1.0 microM respectively) weakly changed the incidence of reperfusion induced arrhythmias. In nicergoline pretreated hearts, in which the incidence of reperfusion arrhythmias was reduced, FeCl3/ADP (0.1/1.0 microM and 1.0/1.0 microM) did not change the incidence and the duration of reperfusion arrhythmias. In normal Purkinje fibres, FeCl3/ADP (0.1/1.0 microM) induced a decrease in action potential duration without any pronounced effect on Vmax, diastolic potential, and activation potential. In Purkinje fibres from post infarct myocardium, FeCl3/ADP decreased action potential duration, diastolic potential, and activation potential.
Conclusions: Free radical generation did not antagonise the antiarrhythmic activity of alpha adrenergic blockade. Free radical generation induced slow and minor changes in electrophysiological activity of Purkinje fibres both from normal and ischaemic hearts. Our data suggest that free radical generation may not be the only mechanism involved in the genesis of reperfusion arrhythmias.