Antiarrhythmic effects of a new drug, E-0747, on canine ventricular arrhythmia models

Antiarrhythmic effects of a new antiarrhythmic drug, E-0747, were examined using four canine ventricular arrhythmia models: digitalis-, adrenaline- and two-stage coronary ligation-induced arrhythmias and a newly developed locally-induced digitalis arrhythmia. The minimum effective plasma concentration of E-0747 was determined for the first three arrhythmia models. E-0747 suppressed those arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by digitalis, adrenaline, 24 hr coronary ligation, and 48 hr coronary ligation were 1.4 +/- 0.6, 1.8 +/- 0.4, 1.6 +/- 0.4 and 2.2 +/- 0.2 micrograms/ml, respectively (mean +/- S.D., n = 5-10). The aforementioned minimum effective plasma concentrations of E-0747 for these arrhythmias were almost equal to the reported concentration in vitro to suppress the Na channels of isolated canine ventricular tissues. The class 1 property of E-0747 was also shown in a newly developed locally-induced digitalis arrhythmia. Thus E-0747 suppresses arrhythmia by inhibiting Na channels of cardiac cells and is expected to become a clinically useful antiarrhythmic drug.