Electrophysiological effects of propafenone in untreated and propafenone-pretreated guinea-pig atrial and ventricular muscle fibres.

Abstract

The electrophysiological effects of propafenone (10(-7) to 10(-4) M) were studied on guinea-pig isolated atrial and ventricular muscle fibres obtained from untreated animals and animals pretreated with propafenone, 3 and 10 mg kg-1, for 28 days. In untreated atria propafenone produced a dose-dependent decrease in the rate and maximum following frequency, prolonged the sinus node recovery time and reduced the maximum chronotropic responses to isoprenaline. In untreated atrial and ventricular muscle fibres propafenone depressed action potential amplitude and Vmax, reduced the resting membrane potential and prolonged the action potential duration (APD) and the effective refractory period, lengthening the effective refractory period relative to APD. Propafenone depressed the amplitude and Vmax and shortened the duration of the slow action potentials induced by isoprenaline and caffeine in K-depolarized papillary muscles. Pretreatment with propafenone reduced atrial rate, but did not modify the action potential characteristics compared to the values obtained in untreated atria. Further addition of propafenone produced similar but more marked changes in untreated atria. In ventricular muscle fibres pretreated with 3 mg kg-1, action potential characteristics before and after further addition of propafenone were similar to those obtained in untreated fibres. However, muscles pretreated with 10 mg kg-1 exhibited a significant prolongation of the APD compared to that in untreated muscles or those pretreated with 3 mg kg-1; further addition of propafenone shortened the APD even when this parameter was of similar value to those observed in the other two series of experiments. It is concluded that even though the effects of propafenone are similar to those of quinidine (class I antiarrhythmic), it also exhibited class II and class IV actions. In pretreated animals a prolongation of the APD (class III action) could also be involved in the antiarrhythmic effects of the drug.