title: Use-dependent electrophysiologic effects of amiodarone in coronary artery disease and inducible ventricular tachycardia.
abstract: Amiodarone produces use-dependent block of cardiac sodium channels in vitro. This study assessed whether similar use-dependent block occurred in 19 patients with coronary artery disease and inducible, sustained, monomorphic ventricular tachycardia treated with amiodarone. Beat-to-beat measurements of ventricular paced QRS durations during 12-beat trains at cycle lengths of 700, 600, 400 and 300 ms were analyzed at a baseline antiarrhythmic drug-free study and after 2 and 10 weeks of amiodarone therapy. At the drug-free study, there were no significant changes in paced QRS durations within the 12-beat trains at any pacing cycle lengths. After 2 and 10 weeks of amiodarone therapy, progressive prolongation of paced QRS durations occurred over the 12-beat trains at pacing cycle lengths of 600, 400 and 300 ms (p less than 0.05). Significant changes in QRS duration were not observed at a pacing cycle length of 700 ms. This progressive prolongation in QRS duration can be fitted as a function of beat number to a monoexponential equation and occurred with an onset time constant of 1.02 +/- 0.41 beats (306 +/- 122 ms) at a pacing cycle length of 300 ms. The magnitude of QRS prolongation increased as the pacing cycle length was shortened. The magnitudes of QRS prolongation were similar after 2 and 10 weeks of amiodarone therapy. In conclusion, use-dependent prolongation in QRS duration occurs at rapid pacing cycle lengths in humans receiving amiodarone.
authors.affiliation: Department of Medicine, University of Calgary, Alberta, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Chiamvimonvat
authors.forename: L B
authors.initials: LB
authors.lastname: Mitchell
authors.forename: A M
authors.initials: AM
authors.lastname: Gillis
authors.forename: D G
authors.initials: DG
authors.lastname: Wyse
authors.forename: R S
authors.initials: RS
authors.lastname: Sheldon
authors.forename: H J
authors.initials: HJ
authors.lastname: Duff
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000188:drug therapy*; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D015222:Sodium Channels / Q000187:drug effects*; D013610:Tachycardia / Q000175:diagnosis / Q000188:drug therapy*; D013997:Time Factors
chemical_list: D015222:Sodium Channels; D000638:Amiodarone