We studied the effect of two new class II antiarrhythmics, ambasilide and dofetilide, on the action potential duration (APD) of guinea pig right ventricular papillary muscle at different extracellular potassium concentrations ([K+e]) and pacing frequencies. Under normal [K+e], both drugs significantly prolonged APD90 (APD at 90% repolarization) at 0.5 Hz. The effect of ambasilide was well preserved at rapid pacing rates, independent of [K+e]. The effect of dofetilide was markedly reduced with increasing pacing rate, especially in high [K+e]. Therefore, ambasilide may be useful in treating tachyarrhythmias in normal, as well as in altered [K+e] conditions.
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