Why the study?
Do d-sotalol and amiodarone have frequency-dependent effects on action potential duration in patients undergoing electrophysiological testing?
Do d-sotalol and amiodarone have frequency-dependent effects on action potential duration in patients undergoing electrophysiological testing?
D-sotalol exhibits reverse use-dependent effects on human ventricular action potential duration, whereas amiodarone prolongs it uniformly across different heart rates.
Amiodarone's rate-independent APD effects may be preferable to d-sotalol's reverse use-dependence; leaves open differential clinical arrhythmia outcomes.
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.
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Huikuri et al. (1992) studied this question.
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