PROLONGATION OF MONOPHASIC ACTION-POTENTIAL DURATION AND THE REFRACTORY PERIOD IN THE HUMAN HEART BY TEDISAMIL, A NEW POTASSIUM-BLOCKING AGENT

The effect of intravenous tedisamil (0.3 mg. kg-1), a newly developed potassium-blocking agent, on ventricular repolarization was studied in 10 patients (three women, seven men; mean; mean age 53 +/- 8 years) w ith coronary artery disease (stenoses less-than-or-equal-to 60%). Left ventricular monophasic action potentials, effective refractory period s and surface electrocardiograms were recorded during sinus rhythm and during constant atrial pacing at cycle lengths of 600, 500 and 400 ms . Under tedisamil there was a 12% reduction of heart rate and in paral lel a prolongation of QTc interval (+ 10%) and left ventricular monoph asic action potential duration (+ 16% at 90% repolarization). QRS dura tion remained unchanged. Tedisamil increased the duration of monophasi c action potentials during constant atrial pacing, indicating a direct prolongation effect on left ventricular repolarization independent of sinus node activity. By increasing the atrial pacing rate this prolon ging effect diminished. Left ventricular effective refractory periods also increased in a frequency-dependent fashion with a greater prolong ation effect at long cycle lengths as compared to short cycle lengths. The ratio between effective refractory period and monophasic action p otential duration, however, remained constant, independent of heart ra te. We conclude that tedisamil is bradycardic at the dose tested and h as a reverse use dependent prolongation effect on left ventricular rep olarization and refractoriness. The electrophysiologic profile is cons istent with a class III antiarrhythmic classification.