The cellular electropharmacology of mexiletine combined with sotalol in porcine papillary muscle and Purkinje fibre. II. Effects on action potential duration and refractoriness

Abstract

Using standard microelectrode techniques, the authors compared the effects of 15 to 125 microM concentrations of mexiletine, 31 to 500 microM concentrations of sotalol and 15 to 125 microM of mexiletine combined with 125 microM sotalol, on the beat-to-beat action potential duration and refractoriness of porcine papillary muscles and Purkinje fibres stimulated by 30 beat trains at a frequency of 1 Hz. Sotalol alone prolonged action potential duration and effective refractory period without altering their ratio. Mexiletine shortened action potential duration while prolonging refractoriness. When the two drugs were combined, action potential duration was shortened to the same extent as with mexiletine alone, but refractoriness, particularly in papillary muscle, was further prolonged. These changes suggest additive inhibition of the sodium window current by both drugs. Purkinje action potential duration was longest in the first beat of the train, while in papillary muscle, this beat was shortest. Exposure to either or both drugs eliminated the prolongation of duration of the first beat of the train in Purkinje fibre. Thus, the phenomenon of restitution, which prolongs the duration of the first beat after a long diastolic interval, appears also to be related to the sodium window current.