CHRONIC AMIODARONE REDUCES TRANSMURAL DISPERSION OF REPOLARIZATION INTHE CANINE HEART

Amiodarone Reduces Transmural Dispersion. Introduction: Amiodarone is a potent antiarrhythmic agent used in the management of both atrial an d ventricular arrhythmias. In addition to its beta-blocking properties , amiodarone is known to block the sodium, potassium, and calcium chan nels in the heart, Its complex electropharmacology notwithstanding, th e reasons for the high efficacy of the drug remain unclear, Also not w ell understood is the basis for the low incidence of proarrhythmia see n with amiodarone relative to other agents with Class III actions, The present study was designed to examine the effects of chronic amiodaro ne in epicardial, endocardial, and M cells of the canine left ventricl e.Methods and Results: We used standard microelectrode techniques to r ecord transmembrane activity from endocardial, epicardial, mid-myocard ial, and transmural strips isolated from the canine left ventricle, Ti ssues were obtained from mongrel dogs receiving amiodarone orally (30 to 40 mg/kg per day) for 30 to 45 days or from untreated controls, Chr onic amiodarone produced a greater prolongation of action potential du ration in epicardium and endocardium, but less of an increase, or even a decrease at slow rates, in the M region, thereby reducing transmura l dispersion of repolarization, In addition, chronic amiodarone therap y suppressed the ability of the I-Kr blocker, d-sotalol, to induce a m arked dispersion of repolarization or early afterdepolarization activi ty. Conclusion: Our data demonstrate for the first time a direct effec t of chronic amiodarone treatment to differentially alter the cellular electrophysiology of ventricular myocardium so as to produce an impor tant decrease in transmural dispersion of repolarization, especially u nder 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 unders tanding of the low incidence of proarrhythmia attending therapy with c hronic amiodarone in comparison with other Class III agents.