Electrophysiological Effects of Penticainide (CM 7857) in Isolated Human Atrial and Ventricular Fibers

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Abstract
The intracellular electrophysiological properties of a new antiarrhythmic agent, penticainide (5 .times. 10-6 to 5 .times. 10-5 M) were studied in isolated driven human right atrial appendage and papillary muscle superfused with oxygenated Tyrode''s solution. In atrial fibers, penticainide decreased the amplitude, maximum rate of rise (dV/dtmax), plateau amplitude, and duration (APD) of action potentials (AP). In ventricular fibers, the main AP modification induced by penticainide was a dV/dtmax diminution. All those effects were frequency and concentration dependent. Penticainide decreased resting potential at 5 .times. 10-5 M only. Ventricular APD variations were relatively weak: in most of the cases, 5 .times. 10-6 M decreased APD and 5 .times. 10-5 M shortened long APD (> 300 ms) and lengthened short APD (< 300 ms). The class I antiarrhythmic property (dV/dtmax decrease) of penticainide was rate dependent in both human fibers and was obtained at lower drug concentrations than those used in other species. The relatively rapid rate of onset and the rather slow recovery kinetics of dV/dtmax block suggest a common mechanism of action of penticainide on sodium channels in human heart and others mammals.