Electrophysiological mechanisms for the antiarrhythmic action of mexiletine on digitalis-, reperfusion- and reoxygenation-induced arrhythmias.

The antiarrhythmic potency of mexiletine was evaluated on three groups of guinea-pig isolated hearts. Arrhythmias were induced (a) with digitalis intoxication, (b) with hypoxia followed by reoxygenation and (c) with ischaemia followed by reperfusion. Mexiletine 10 microM was found to be very effective against all three types of arrhythmias in all three groups. The electrophysiological effects of mexiletine were then studied on sheep cardiac Purkinje fibres manifesting oscillatory afterpotentials and triggered automaticity induced by barium or strophanthidin. Mexiletine 10 microM consistently decreased the amplitude of oscillatory afterpotentials and blocked subsequent triggered activity in sheep Purkinje fibres. In contrast, mexiletine 10 microM had no significant effect on Vmax in normal, barium- and strophanthidin-treated preparations. The results are discussed in relation to the mechanisms of antiarrhythmic action of mexiletine.