Effects of azimilide, a KV(r) and KV(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-methyl-1-piperazinyl)butyl]-2,4-imidazolidi nedione dihydrochloride. The coronary 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 ligation (35 +/- 17 beats/30 min as compared with 909 +/- 246 in the control group), and also suppressed ventricular fibrillation induced by coronary ligation/reperfusion in the two groups (1/8 halothane-anesthetized dogs as compared with 7/8 dogs in the control group and 2/8 pentobarbital-anesthetized dogs as compared with 8/8 dogs in the control group). In adrenaline arrhythmia, azimilide hastened the onset of adrenaline arrhythmias and also aggravated the arrhythmias, showing proarrhythmic effects.
Xue
Y
Y
Department of Pharmacology, Yamanashi Medical University, Japan.
Yamada
C
C
Chino
D
D
Hashimoto
K
K
D000777:Anesthetics; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004285:Dogs; D004837:Epinephrine; D005260:Female; D006221:Halothane; D006827:Hydantoins; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D048289:Imidazolidines; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications; D010424:Pentobarbital; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D026902:Potassium Channel Blockers; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control
D000777:Anesthetics; D000889:Anti-Arrhythmia Agents; D006827:Hydantoins; D007093:Imidazoles; D048289:Imidazolidines; D010879:Piperazines; D026902:Potassium Channel Blockers; C086123:azimilide; D010424:Pentobarbital; D006221:Halothane; D004837:Epinephrine