Effects of dofetilide, a class III antiarrhythmic drug, on various ventricular arrhythmias in dogs.
Dofetilide, a new class III antiarrhythmic agent, was tested in various kinds of canine ventricular arrhythmias to compare its effects with those of other class III agents. Ventricular arrhythmia models used were induced by two-stage coronary ligation, digitalis, epinephrine, coronary ligation and reperfusion, and programmed electrical stimulation (PES). Dofetilide (100 micrograms/kg intravenously) did not suppress automaticity arrhythmias induced by two-stage coronary ligation and epinephrine or the coronary ligation and reperfusion arrhythmias, but suppressed the reentry arrhythmia induced by PES in dogs with old myocardial infarction (MI). This effect was associated with a prolongation of QT interval. Dofetilide also showed antiarrhythmic effect in some dogs with digitalis arrhythmia. Dofetilide increased QT interval and showed negative chronotropic effect like that of other class III drugs, but was different in antiarrhythmic profiles from those of other class III agents such as D-sotalol, E-4031, and MS-551 in that it did not prevent the occurrence of ventricular fibrillation (VF) immediately after coronary reperfusion and had some antiarrhythmic effects on digitalis arrhythmia.
Chen
J
J
Department of Pharmacology, Yamanashi Medical University, Japan.
Xue
Y
Y
Eto
K
K
Ni
C
C
Hashimoto
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000188:drug therapy*; D003331:Coronary Vessels / Q000601:surgery; D004070:Digitalis; D004195:Disease Models, Animal; D004285:Dogs; D004558:Electric Stimulation; D004562:Electrocardiography; D004837:Epinephrine; D005260:Female; D008297:Male; D009203:Myocardial Infarction; D015425:Myocardial Reperfusion; D010627:Phenethylamines / Q000627:therapeutic use*; D010946:Plants, Medicinal; D010947:Plants, Toxic; D013449:Sulfonamides / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000188:drug therapy; D014693:Ventricular Fibrillation / Q000188:drug therapy
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; C063533:dofetilide; D004837:Epinephrine