Effects of azimilide, a K-V(r) and K-V(s) blocker, on canine ventricular arrhythmia models

Using canine coronary artery ligation/reperfusion and adrenaline arrhythmia models, we determined the effects of azimilide, a class III antiarrhythmic agent, E-1-{[(5-(4-chlorophenyl)-2-furanyl) methylene]-amino}-3-[4-(4- met hyl-1-piperazinyl)butyl]-2,4-imidazolidinedione dihydrochloride. The corona ry ligation/reperfusion arrhythmia experiments were divided into two groups , one using low heart rate halothane-anesthetized and the other using high heart rate pentobarbital-anesthetized dogs. Azimilide (6 mg kg(-1) + 0.1 mg kg(-1) min(-1) i.v.) prolonged the corrected QT interval (QTc), decreased the heart rate and suppressed the premature ventricular complexes during Li gation (35 +/- 17 beats/30 min as compared with 909 +/- 246 in the control group), and also suppressed ventricular fibrillation induced by coronary li gation/reperfusion in the two groups (1/8 halothane-anesthetized dogs as co mpared with 7/8 dogs in the control group and 2/8 pentobarbital-anesthetize d dogs as compared with 8/8 dogs in the control group). In adrenaline arrhy thmia, azimilide hastened the onset of adrenaline arrhythmias and also aggr avated the arrhythmias, showing proarrhythmic effects. (C)1999 Elsevier Sci ence B.V. All rights reserved.