Circulation, Vol 80, 34-42, Copyright © 1989 by American Heart Association
LB Mitchell, DG Wyse, AM Gillis and HJ Duff
The time courses of onset of the electrophysiologic and antiarrhythmic
effects of amiodarone were determined with serial electrophysiologic
studies in 34 patients with inducible ventricular tachycardia. A
standardized oral loading dosage was used for all patients (1,200 mg/day
for 14 days; 800 mg/day for 7 days; and 400 mg/day thereafter). Eleven
patients had the studies performed at baseline and after 2, 6, 10, and 20
weeks. Subsequently, 23 patients had studies at baseline and after 2 and 10
weeks. Changes in atrial, sinus, and atrioventricular nodal properties and
in conduction intervals were maximal within 2 weeks (early effects). For
example, atrioventricular nodal Wenckebach cycle length increased between
baseline (369 +/- 80 msec) and 2 weeks (498 +/- 78 msec) (p less than
0.001) but did not change further after 10 weeks (500 +/- 89 msec).
However, ventricular Class III effects required 10 weeks to become maximal
(late effects). For example, the QT interval during atrial pacing increased
between baseline (355 +/- 36 msec) and 2 weeks (406 +/- 37 msec) (p less
than 0.001) and increased further after 10 weeks (436 +/- 45 msec) (p less
than 0.001). Antiarrhythmic effects also followed different time courses of
onset. Suppression of ventricular premature beats was maximal within 2
weeks. However, suppression of ventricular tachycardia inducibility and
slowing of ventricular tachycardia rate was not maximal for 10 weeks.
Correlations between serum desethylamiodarone concentrations and some late
effects suggest that the mechanism of the time delay to maximal ventricular
Class III effects may involve desethylamiodarone.(ABSTRACT TRUNCATED AT 250
WORDS)
ARTICLES
Electropharmacology of amiodarone therapy initiation. Time courses of onset of electrophysiologic and antiarrhythmic effects
Department of Medicine, Foothills General Hospital, Calgary, Alberta, Canada.
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