The effects of acute amiodarone on short- and long-duration ventricular defibrillation threshold in canines

J Cardiovasc Pharmacol. 2011 Oct;58(4):432-8. doi: 10.1097/FJC.0b013e318228a50c.

Abstract

Introduction: Some studies have shown that the defibrillation threshold (DFT) differs between short-duration ventricular fibrillation (SDVF, <1 minute) and long-duration ventricular fibrillation (LDVF > 1 minute). The goal of this study is to evaluate the effects of acute intravenous amiodarone on SDVF-DFT and LDVF-DFT and its possible mechanism as well.

Methods: Twelve open-chest dogs were randomly divided into 2 groups (control group, normal saline, 10 mL·kg·h maintenance, n = 6; amiodarone group, loading dose 10 mg/kg over 10 minutes, maintenance dose 5 mg·kg·h, n = 6). VF was electrically induced and recorded with a 12 × 12 unipolar electrode plaque (2-mm spacing) sutured on the left ventricular epicardium and a plunge needle (6 unipolar electrode) inserted in the left ventricular apex. The DFTs of SDVF and LDVF were determined 20 seconds and 3 minutes after VF induction, respectively. Restitution was estimated from activation recovery intervals during pacing from the plaque and plunge needle electrodes. The activation rate was estimated by Fast Fourier Transform analysis of VF at same electrodes. The VF cycle length was defined as the reciprocal of the activation rate. The epicardial and transmural dispersion of the maximal slope of the restitution curve and VF cycle length of SDVF and LDVF were calculated, respectively.

Results: : In controls, LDVF-DFT was higher than SDVF-DFT (645 ± 61 vs. 520 ± 63 V, P < 0.01). Amiodarone did not significantly alter SDVF-DFTs (496 ± 49 vs. 552 ± 69 V, P > 0.05) but decreased LDVF-DFT by 31% (P < 0.01). Compared with control, amiodarone significantly reduced the maximum slope of the restitution curve (1.12 ± 0.35 vs. 0.81 ± 0.25, P = 0.03) and its epicardial dispersion (0.32 ± 0.07 vs. 0.24 ± 0.04,coefficient of variation, P = 0.017). Amiodarone significantly increased the SDVF-CL (92 ± 8 vs. 99 ± 10 milliseconds, P < 0.01) and epicardial dispersion 0.14 ± 0.06 vs. 0.18 ± 0.05, P < 0.01. Amiodarone did not change the LDVF-CL (228 ± 12 vs. 226 ± 10 milliseconds, P > 0.05) or epicardial dispersion (0.17 ± 0.03 vs. 0.15 ± 0.02, P > 0.05) compared with control. However, the drug significantly decreased the transmural dispersion of LDVF-CL (68 ± 28 vs. 39 ± 14 milliseconds, P < 0.01) without changing the transmural dispersion of SDVF-CL (29 ± 22 vs. 32 ± 30 milliseconds, P > 0.05).

Conclusions: Acute amiodarone significantly decreased the LDVF-DFT. The decreased transmural dispersion of LDVF-CL by amiodarone might contribute to the decreased LDVF-DFT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiodarone / administration & dosage
  • Amiodarone / pharmacology*
  • Animals
  • Anti-Arrhythmia Agents / administration & dosage
  • Anti-Arrhythmia Agents / pharmacology*
  • Disease Models, Animal
  • Dogs
  • Electric Countershock
  • Fourier Analysis
  • Infusions, Intravenous
  • Random Allocation
  • Time Factors
  • Ventricular Fibrillation / drug therapy*
  • Ventricular Fibrillation / physiopathology

Substances

  • Anti-Arrhythmia Agents
  • Amiodarone