<SHORT REPORTS>Effects of New Class-III Antiarrhythmic Agents, E-4031 and MS-551, on Ventricular Repolarization in Rabbit Hearts

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The effects of E-4031 and MS-551 on ventricular repolarization were investigated in Langendorff-perfused rabbit hearts. Fifteen to twenty electrograms were recorded through modified bipolar electrodes from the anterior epicardial surface of the left ventricle under His-bundle pacing at 1.0 Hz. In control group hearts, epicardial activation proceeded from the apex to the base. The interval from the initial sharp negative deflection to the apex of the T-wave(Q-aT) in the epicardial electrogram, which reflects action potential duration at the recording site, was longest at the apex and shortest at the base. Repolarization, therefore, proceeded from the base to the apex. Acute application of E-4031 (0.1μM)or MS-551 (1μM) induced a prolongation of Q-aT in the left ventricle without affecting the activation sequence. The Q-aT prolongation by E-4031 was longer in the apex than in the base, giving rise to a singnificant enhancement of spatial inhomogeneity of repolarization. MS-551 caused only a minimal increase in the spatial inhomogeneity of repolarization. These results could be attributed to the agnets' differing effects on the outward currents responsible for repolarization of ventricular cells.
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