Rate-independent effects of the new class III antiarrhythmic agent ambasilide on transmembrane action potentials in human ventricular endomyocardium.

The electrophysiologic effects of ambasilide, a new class III antiarrhythmic drug reported to be a nonselective blocker of both components (I(Kr) and I(Ks)) of the delayed-rectifier potassium current (I(K)) and other repolarizing potassium currents (I(tol), I(so)), were studied in specimens of left ventricular endomyocardium of human hearts obtained from 10 patients undergoing either heart transplantation (n = 4) or mitral valve replacement (n = 6). We recorded transmembrane action potential (TAP) characteristics at different stimulation frequencies (0.5, 1, 1.5, and 2 Hz) and with different dosages of ambasilide (1, 10, and 50 microM) by using conventional microelectrode techniques. Beginning at a concentration of 10 microM ambasilide, the TAP duration at 90% repolarization (TAPD90) was significantly prolonged and independent of stimulation frequency with a mean percentage prolongation of 18% at 10 microM and 30% at 50 microM ambasilide. TAP duration at 50% repolarization was not significantly prolonged except for 10 microM ambasilide at 0.5 Hz (17%; p < 0.05). The frequency-independent action potential (AP) prolongation by ambasilide in human ventricular endomyocardium indicates that a nonselective block of repolarizing potassium currents seems to be more favorable than a selective block of I(Kr).