Effect of pentisomide (CM 7857) on myocardial excitation, conduction, repolarization, and refractoriness. An electrophysiological study in humans

Abstract

The electrophysiological effects of pentisomide upon the intact human heart were evaluated using programmed stimulation and recording of intracardiac monophasic action potentials (MAP) in 17 patients with various ventricular arrhythmias. After i.v. administration of pentisomide, 85-135 mg, the atrial-His interval increased by 8 +/- 12 ms (p less than 0.05) during sinus rhythm and by 13 +/- 21 ms (p less than 0.05) at atrial pacing of 600 ms cycle length (600 ms pacing). The His-ventricular interval also increased by 6 +/- 10 ms during sinus rhythm (p less than 0.05) and by 5 +/- 9 ms at 600 ms pacing (NS). The QRS duration prolonged by 9 +/- 10 ms (p less than 0.01) and 6 +/- 8 ms (p less than 0.01) during 600 and 500 ms ventricular pacing, respectively. The right ventricular MAP duration to 90% repolarization was significantly shortened, by 20 +/- 21 ms (p less than 0.01) during sinus rhythm, by 16 +/- 17 ms (p less than 0.01) at 600 ms ventricular pacing, and by 11 +/- 16 ms (p less than 0.01) at 500 ms ventricular pacing. The corrected QT interval was shortened by 21 +/- 28 ms (p less than 0.01). The present study supports that pentisomide is a class-I antiarrhythmic agent with a marked effect on depolarization (action of class Ia and Ic) and on repolarization (action of class Ib). This unique combination of cellular electrophysiological properties indicates that the clinical antiarrhythmic efficacy of pentisomide may differ from that of hitherto available antiarrhythmic drugs.