title: Effects of amiodarone and its active metabolite desethylamiodarone on the ventricular defibrillation threshold.
abstract: OBJECTIVE
  We evaluated whether the reported difference in the ventricular defibrillation threshold (DFT) between short-term intravenous and oral amiodarone is due to the effect of amiodarone's active metabolite desethylamiodarone (DEA).
  
  
  BACKGROUND
  Amiodarone is frequently used in patients with implantable cardioverter-defibrillator devices (ICD). Long-term oral amiodarone raises the DFT, but intravenous amiodarone has not been shown to have this effect. DEA, an active metabolite of amiodarone, has different electrophysiologic properties than its parent compound and may be responsible for the observed different effects of intravenous and oral amiodarone on DFT.
  
  
  METHODS
  We ascertained the DFT in 24 pigs randomized to receive intravenous amiodarone, DEA or vehicle. Defibrillation was delivered through a transvenous lead system using a biphasic waveform. The DFT was determined using an up-down DFT algorithm and defined as the average minimal energies resulting in successful defibrillation delivered from ascending and descending serial shocks.
  
  
  RESULTS
  Amiodarone caused a dose-response increase in DFT (mean +/- SD) from 22.7 +/- 4.1 (baseline) to 26.1 +/- 2.9 (10 mg/kg body weight), p = 0.11, to 34.9 +/- 8.2 J (after an additional 15 mg/kg), p = 0.035. DEA (10 mg/kg) caused an increase in DFT from 20.5 +/- 6.3 to 33.9 +/- 13.6 J, p < 0.01. Addition of 15 mg/kg of DEA resulted in hemodynamic instability and thus DFT was not obtained. In the control group, DFT decreased from 26.8 +/- 7.7 at baseline to 23.1 +/- 7.4 (dose 1), p = 0.19, to 22.8 +/- 6.2 J (dose 2), p = 0.18.
  
  
  CONCLUSIONS
  DEA increases DFT by a greater amount than its parent drug amiodarone. There is an effect of intravenous amiodarone on DFT that is dose dependent.
authors.affiliation: Department of Pharmacy Services, Hartford Hospital, Connecticut 06102-5037, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: B P
authors.initials: BP
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Kluger
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.forename: M S
authors.initials: MS
authors.lastname: Chow
mesh_terms: D000638:Amiodarone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000097:blood / Q000494:pharmacology*; D004562:Electrocardiography; D006329:Heart Conduction System / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D013552:Swine
chemical_list: D000889:Anti-Arrhythmia Agents; C036116:desethylamiodarone; D000638:Amiodarone