EFFECT OF PENTISOMIDE (CM-7857) ON MYOCARDIAL EXCITATION, CONDUCTION, REPOLARIZATION, AND REFRACTORINESS - AN ELECTROPHYSIOLOGICAL STUDY IN HUMANS

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 < 0.05) during sinus rhythm and by 13 +/- 21 ms (p < 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 < 0.05) and by 5 +/- 9 ms at 600 ms pacing (NS). The QRS duration prolonged by 9 +/- 10 ms (p < 0.01) and 6 +/- 8 ms (p < 0.01) during 600 and 500 ms ventricular pacing, respectively. The fight ventricular MAP duration to 90% repolarization was significantly shortened, by 20 +/- 21 ms (p < 0.01) during sinus rhythm, by 16 +/- 17 ms (p < 0.01) at 600 ms ventricular pacing, and by 11 +/- 16 ms (p < 0.01) at 500 ms ventricular pacing. The corrected QT interval was shortened by 21 +/- 28 ms (p < 0.01). The present study supports that pentisomide is a class-I antiarrhythmic agent with a marked effect on depolarization (action of class la 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.