Delay by a calcium antagonist, amlodipine, of the onset of primary ventricular fibrillation in myocardial ischemia.
Calcium antagonists have been reported to counteract the increase by ischemia of vulnerability to ventricular fibrillation. This ability might be especially of interest in the prevention of sudden death subsequent to a major, but transitory, inadequacy between myocardial oxygen requirements and available coronary blood flow produced by exercise, emotion, etc., because death is then not related to irreversible damage of myocardial fibers. This study has been undertaken to examine the protective effect of a calcium antagonist on an animal model of this type of ischemia. This model used complete, but transient occlusion of the left anterior descending coronary artery near its origin during pacing at a constant high rate (180 beats/min) in anesthetized, open-chest pigs, most often resulting in fibrillation within 1-2 minutes after a progressive fall of the electrical fibrillation threshold. Amlodipine was the preferred calcium antagonist for this study because it is only moderately negatively inotropic. The results of the preventive administration of amlodipine was assessed by the time to onset of fibrillation. Amlodipine 0.30 mg/kg prolonged this time by 50-100% (p < 0.05) without appreciable impairment of blood pressure or myocardial contractility. Concurrently, amlodipine delayed the shortening of the monophasic action potential duration, the lengthening of conduction time, and the alterations of ST segments and T waves linked to ischemic depolarization. Consequently, when given experimentally before the occurrence of major, but transitory ischemia, amlodipine protected against fibrillation. Similarly, in clinical settings it ought to delay sudden death that may occur as a result of a major but transitory inadequacy between myocardial oxygen requirements and available coronary blood flow.
Timour
Q
Q
Department of Medical Pharmacology, Cl. Bernard University, Lyon, France.
Bui-Xuan
B
B
Faucon
G
G
Aupetit
J F
JF
D000200:Action Potentials; D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D017202:Myocardial Ischemia / Q000150:complications*; D013552:Swine; D014693:Ventricular Fibrillation / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D002121:Calcium Channel Blockers; D017311:Amlodipine