EFFECTS OF DOFETILIDE, A CLASS-III ANTIARRHYTHMIC DRUG, ON VARIOUS VENTRICULAR ARRHYTHMIAS IN DOGS

Dofetilide, a new class III antiarrhythmic agent, was tested in variou s kinds of canine ventricular arrhythmias to compare its effects with those of other class III agents. Ventricular arrhythmia models used we re induced by two-stage coronary ligation, digitalis, epinephrine, cor onary ligation and reperfusion, and programmed electrical stimulation (PES). Dofetilide (100 mu g/kg intravenously) did not suppress automat icity arrhythmias induced by two-stage coronary ligation and epinephri ne or the coronary ligation and reperfusion arrhythmias, but suppresse d the reentry arrhythmia induced by PES in dogs With Old myocardial in farction (MI). This effect was associated with a prolongation of QT in terval. Dofetilide also showed antiarrhythmic effect in some dogs with digitalis arrhythmia. Dofetilide increased QT interval and showed neg ative chronotropic effect like that of other class III drugs, but was different in antiarrhythmic profiles from those of other class III age nts such as D-sotalol, E-4031, and MS-551 in that it did not prevent t he occurrence of ventricular fibrillation(VF) immediately after corona ry reperfusion and had some antiarrhythmic effects on digitalis arrhyt hmia.