Chronic Amiodarone Reduces Transmural Dispersion of Repolarization in the Canine Heart

Amiodarone Reduces Transmural Dispersion. Introduction: Amiodarone is a potent antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias. In addition to its β‐blocking properties, amiodarone is known lo block the sodium, potassium, and calcium channels in the heart. Its...

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Published in:Journal of cardiovascular electrophysiology 1997-11, Vol.8 (11), p.1269-1279
Main Authors: SICOURI, SERGE, MORO, SANDRA, LITOVSKY, SILVIO, ELIZARI, MARCELO V., ANTZELEVITCH, CHARLES
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
afterdepolarization
Amiodarone - pharmacokinetics
Amiodarone - pharmacology
Animals
Anti-Arrhythmia Agents - pharmacology
cardiac arrhythmias
cardiac electrophysiology
Dogs
early
endocardium
epicardium
Heart - drug effects
Heart - physiology
M cells
Male
triggered activity
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Summary:Amiodarone Reduces Transmural Dispersion. Introduction: Amiodarone is a potent antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias. In addition to its β‐blocking properties, amiodarone is known lo block the sodium, potassium, and calcium channels in the heart. Its complex electropharmacology notwithstanding, the reasons for the high efficacy of the drug remain unclear. Also not well understood is the basis for the low incidence of proarrhythmia seen with amiodarone relative to other agents with Class III actions. The present study was designed to examine the effects of chronic amiodarone in epicardial, endocardial, and M cells of the canine left ventricle. Methods and Results: We used standard microelectrode techniques to record transmembrane activity from endocardial, epicardial, mid‐myocardial, and transmural strips isolated from the canine left ventricle. Tissues were obtained from mongrel dogs receiving amiodarone orally (30 to 40 mg/kg per day) for 30 to 45 days or from untreated controls. Chronic amiodarone produced a greater prolongation of action potential duration in epicardium and endwardium, but less of an increase, or even a decrease at slow rates, in the M region, thereby reducing transmural dispersion of repolarization. In addition, chronic amiodarone therapy suppressed the ability of the Ikr, blocker, d‐sotalol, to induce a marked dispersion of repolarization or early afterdepolarization activity. Conclusion: Our data demonstrate for the first time a direct effect of chronic amiodarone treatment to differentially alter the cellular electrophysiology of ventricular myocardium so as to produce an important decrease in transmural dispersion of repolarization, especially under conditions in which dispersion is exaggerated. These results may contribute to our understanding of the effectiveness of amiodarone in the treatment of life‐threatening arrhythmias as well as to our understanding of the low incidence of proarrhythmia attending therapy with chronic amiodarone in comparison with other Class III agents.
ISSN:1045-3873
1540-8167
DOI:10.1111/j.1540-8167.1997.tb01018.x