Differential class III antiarrhythmic effects of ambasilide and dofetilide at different extracellular potassium and pacing frequencies

We studied the effect of two new class III 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 APD ₉₀ (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.