Frequency dependent effects of d-sotalol and amiodarone on the action potential duration of the human right ventricle.
Frequency dependent effects of d-Sotalol (2.0 mg/kg IV, n = 6) and amiodarone (400 mg/day for 3 months, n = 9) were studied on the action potential duration (APD) in 14 patients who underwent electrophysiological testing. Monophasic action potentials were recorded from the right ventricle at five different steady-state paced cycle lengths (700 msec, 600 msec, 500 msec, 400 msec, and 350 msec), and during ventricular extrastimuli with coupling intervals between 300 msec and 1000 msec, before and after d-sotalol and amiodarone, respectively. D-sotalol caused a prolongation of the APD at slow steady-state stimulation rates (11 +/- 5% at cycle length of 700 msec), which became attenuated at faster cycle lengths (5 +/- 3% at cycle length of 350 msec). Prolongation of APD after amiodarone was independent of pacing rate, e.g., 12 +/- 9% at cycle length of 700 msec, and 11 +/- 6% at cycle length of 350 msec. Similar frequency dependent prolongation of the APD was observed during abrupt changes of cycle lengths after d-sotalol, whereas amiodarone caused uniform prolongation of the APD at different extrastimulus intervals. Thus, d-sotalol, a nonselective potassium channel blocker, has reverse use-dependent effects on the human ventricular APD, while amiodarone with greater potassium channel selectivity, has equal ability to prolong the ventricular APD at fast and slow heart rates.
D000200:Action Potentials / Q000187:drug effects; D000284:Administration, Oral; D000368:Aged; D000638:Amiodarone / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015221:Potassium Channels / Q000187:drug effects; D013015:Sotalol / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000188:drug therapy*; D014693:Ventricular Fibrillation / Q000188:drug therapy*; D016278:Ventricular Function, Right / Q000187:drug effects*
D015221:Potassium Channels; D013015:Sotalol; D000638:Amiodarone