Effect of mexiletine, amiodarone and disopyramide on the excitability and refractoriness of canine cardiac fibers: possible relation to antiarrhythmic drug action and classification.

We tested the hypothesis of Campbell that the effect of the sodium channel-blocking antiarrhythmic drugs on postrepolarization refractoriness i.e., relation between action potential duration (APD) and effective refractory period (ERP) is determined by the drug's effect on the recovery from Vmax block. We studied the effects of two antiarrhythmic drugs with fast (mexiletine, amiodarone), and one with slow (disopyramide) kinetics of recovery from Vmax block, at two different basic cycle lengths (BCL), on ERP/APD ratio in cardiac dog Purkinje and ventricular muscle fibers. ERP was measured using stimuli of 2 ms duration and 1.0 to 5.0 times diastolic threshold strength. The three drugs altered the kinetics of recovery from Vmax block in the manner previously reported by us and other investigators. In both fiber types, mexiletine increased and the other two drugs did not change the ERP/APD ratio. We concluded that the magnitude of postrepolarization refractoriness could not be predicted from the kinetics of the Vmax block. Also, the effect of the drug on the ERP/APD ratio could be altered by changes in the stimulus strength and the BCL.