Effects of long-term oral administration of amiodarone on the ventricular repolarization of rabbit hearts

The chronic effects of amiodarone on ventricular repolarization were investigated in Langendorff-perfused rabbit hearts in comparison with the acute effects of other Class III antiarrhythmic drugs. Forty to fifty electrograms were recorded through modified bipolar electrodes from the anterior to the lateral epicardial surface of the ventricles under His-bundle pacing (1.0 Hz). In control hearts, epicardial activation proceeded from the apex to the base. The interval from the initial sharp negative deflection of the QRS complex to the apex of the T-wave (Q-aT), which reflects the action potential duration (APD) at the recording site, was longest in the apex and shortest in the base. Therefore, repolarization proceeded from the base to the apex. In hearts treated with oral amiodarone (100 mg/kg, 4 weeks), Q-aT was uniformly prolonged by 14-16% throughout the entire mapped area, whereas the activation sequence was unaffected, and a normal Q-aT gradient was well preserved from the apex to the base. The spatial inhomogeneity of left ventricular repolarization was not enhanced by drug treatment. Acute application of sotalol (30 mu mol/L), E-4031 (0.1 mu mol/L) or MS-551 (1.0 mu mol/L) caused a much greater Q-aT prolongation in the apex than in the base, resulting in a marked enhancement of the spatial inhomogeneity of repolarization. These findings suggest that the propensity of chronic amiodarone to induce torsade de pointes less often than other Class III agents may result at least in part from its favorable effect on the spatial homogeneity of ventricular repolarization.