[SHORT REPORTS]Effects of a New Class-III Antiarrhythmic Agent, Sematilide, on Ventricular Repolarization in Rabbit Hearts

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The effects of sematilide on ventricular repolarization were investigated in Langendorff-perfused rabbit hearts. Forty to fifty electrograms were recorded through modified bipolar electrodes from anterior and lateral epicardial surfaces of the right and left ventricles under His-bundle pacing at 1.0 Hz.In the control hearts, epicardial activation appeared near the apex of the right ventricle and proceeded toward the base. The interval from the initial sharp negative deflection to the apex of the T-wave (Q-aT) in the epicardial electrograms, which reflects the action potential duration at the recording site, was longest at the apex and shortest at the base. Repolarization, thus, proceeded from the base to the apex. Application of sematilide (10 μM) induced a prolongation of Q-aT in both ventricles without affecting the activation sequence. The Q-aT prolongation by sematilide was longer in the apex than in the base, giving rise to a significant enhancement of spatial inhomogeneity in the repolarization. Possible mechanisms and the clinical implication of such regional differences in the Class-III action of this antiarrhythmic drug are discussed.
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