Ventricular Arrhythmias Following Exposure of Failing Hearts to Oxidative Stress in Vitro

INTRODUCTION: There is experimental evidence that heart failure (HF) is an oxidative stress and that HF myocytes may be damaged by oxygen-derived free radicals. However, the arrhythmogenicity of these radicals has not been studied in HF. METHODS AND RESULTS: Isolated perfused hearts were obtained from sham-operated (SHAM, n = 6), and fast pacing (250 ms, 2 weeks)-induced heart failure porcines (HF, n = 8). Epicardial conduction was mapped in the longitudinal and transverse directions and ventricular arrhythmias were closely monitored after perfusion of 100, 300, and 1000 micromol/L H(2)O(2). Left ventricular epicardium was sampled for action potentials recordings in the same conditions. Myocardial levels of thiobarbituric acid reactive substances and antioxidant enzymatic capacity were also assessed. Epicardial conduction velocities were unaffected by H(2)O(2) in both groups. Isolated ventricular premature beats and runs of slow ventricular rhythm with H(2)O(2) more frequently occurred in HF compared to SHAM despite an increased antioxidant capacity including Cu/Zn and Mn superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase. Sustained arrhythmias were not observed. Higher thiobarbituric acid reactive substances levels were found in HF confirming endogenous oxidative stress. Action potential duration at plateau level was increased following H(2)O(2) in SHAM but not in HF epicardial fibers where a toxic effect developed at 1000 micromol/L. CONCLUSION: Oxidative stress with concomitant increase in antioxidant capacity develops in this HF model. There is a greater proclivity to oxidative stress-mediated arrhythmias in HF. These arrhythmias are mainly extrasystoles or slow ventricular rhythms and not dependent on abnormal myocardial conduction.