[SHORT REPORTS]Frequency-Dependent Effects of a New Class-III Antiarrhythmic Agent, Sematilide, on the Action Potential Duration of Rabbit Ventricular Muscles

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The effects of a newly developed Class-III antiarrhymic agent, sematilide, on the action potential configuration were investigated in isolated rabbit papillary muscles. Sematilide (10 μM and 30 μM) caused a concentration-dependent prolongation of the action potential duration (APD) without affecting either the maximum upstroke velocity or the resting membrane potential. Contractile force of the muscle was increased moderately. The steady-state APD prolongation by sematilide enhanced progressively at the lower stimulation frequency, resulting in a market reverse frequency-dependence. In muscles subjects to a stimulation train (0.5 Hz) following a long rest period, the APD prolongation by sematilide was recognized from the first beat; there was no beat-to-beat enhancement of the drug-induced APD prolongation during the train. These findings suggest that a potassium channel block by sematilide may not possess use-dependent characteristics.
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