title: Effects of chronic amiodarone on the electrical restitution in the human ventricle with reference to its antiarrhythmic efficacy.
abstract: BACKGROUND
  Dynamic instability of ventricular refractoriness represented by electrical restitution operates synergistically with tissue heterogeneity to increase the propensity for functional reentry leading to ventricular tachycardia/fibrillation (VT/VF). Little is known about the effect of chronic amiodarone on the electrical restitution in the human ventricle.
  
  
  RESULTS
  Restitution kinetics of monophasic action potential duration (MAPD(90)) in the right ventricular outflow tract (RVOT) and apex (RVA), and of inverse of conduction time from RVOT to RVA (CT(-1)), were estimated by an S1-S2 protocol in 22 patients treated with amiodarone (180 ± 33 mg/day for 7 ± 9 months) and in 30 without treatment. In the untreated patients, the restitution kinetics of CT(-1) was steeper in the group with structural heart disease (SHD) (UNT(SHD+), n = 18) than without SHD (UNT(SHD-), n = 12), whereas MAPD(90) restitution parameters were comparable. In the amiodarone-treated patients (all with SHD), the shortest diastolic interval to produce a ventricular response (DI(min)) was increased, the maximum slope of MAPD(90) was flattened, and the magnitude of CT(-1) restitution was reduced as compared with UNT(SHD+). Sustained VT/VF was induced in 7 of 18 UNT(SHD+) (38.9%) and in 4 of 22 amiodarone-treated patients (18.2%, P = 0.07). Concomitant presence of increased CT(-1) restitution and dispersion of MAPD(90) restitution was required for the VT/VF induction. The suppression of VT/VF in the amiodarone-treated patients was associated with a smaller magnitude of CT(-1) restitution in the presence of limited dispersion of MAPD(90) restitution.
  
  
  CONCLUSIONS
  Chronic amiodarone flattens restitution kinetics of MAPD(90) and CT(-1) in the human ventricle, which could be antiarrhythmic in patients with limited tissue heterogeneity.
authors.affiliation: Division of Arrhythmia and Electrophysiology, Shizuoka Saiseikai General Hospital, Suruga-ku, Shizuoka, Japan. toshi.osaka@nifty.com
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Osaka
authors.forename: Eriko
authors.initials: E
authors.lastname: Yokoyama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Hasebe
authors.forename: Itsuo
authors.initials: I
authors.lastname: Kodama
mesh_terms: D000638:Amiodarone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D014693:Ventricular Fibrillation / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D000638:Amiodarone