Effects of long-term amiodarone treatment on ventricular-fibrillation vulnerability and defibrillation efficacy in response to monophasic and biphasic shocks.
Antiarrhythmic drugs, most notably amiodarone, are often used to combat life-threatening tachyarrhythmias simultaneous with implantable cardioverter defibrillators. However, the effects of long-term amiodarone treatment on ventricular fibrillation (VF) vulnerability and the defibrillation threshold (DFT) remain incompletely understood. VF vulnerability and the DFF for monophasic and biphasic shocks were studied in 10 isolated perfused hearts of rabbits treated over the long term with amiodarone (50 mg/kg/day orally for 28 days) before the experiment. The results were compared with those of a control group (n = 10). Monophasic action potentials were recorded from 10 sites simultaneously to determine ventricular activation and repolarization. Myocardial tissue concentrations were 17.1 +/- 14.8 microg/g for amiodarone and 4.6 +/- 4.4 microg/g for desethylamiodarone. Amiodarone treatment prolonged action-potential duration by 12.9 ms (p = 0.025) and ventricular repolarization by 16.5 ms (p = 0.03) without changing ventricular activation and dispersion of repolarization. Amiodarone treatment caused a rightward shift of the vulnerable window for monophasic and biphasic shocks by 13-17 ms (p < 0.05). The width of the vulnerable window, the upper (ULV) and lower (LLV) limits of VF vulnerability, and the DFT remained unchanged. The fact that ULV and DFT remained unchanged suggests that the ULV still may be valid surrogate for the DFT during long-term amiodarone therapy.
Behrens
S
S
Cardiology Division of the VA Medical Center and Georgetown University, Washington, DC 20422, U.S.A.
Li
C
C
Franz
M R
MR
D000638:Amiodarone / Q000627:therapeutic use*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D004554:Electric Countershock / Q000592:standards; D006334:Heart Function Tests; D008297:Male; D011817:Rabbits; D014693:Ventricular Fibrillation / Q000188:drug therapy* / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone