Cardiac Electrophysiological Alterations in Heart/Muscle-Specific Manganese-Superoxide Dismutase-Deficient Mice: Prevention by a Dietary Antioxidant Polyphenol

摘要

Cardiac electrophysiological alterations induced by chronic exposure to reactive oxygen species and protective effects of dietary antioxidant have not been thoroughly examined. We recorded surface electrocardiograms (ECG) and evaluated cellular electrophysiological abnormalities in enzymatically-dissociated left ventricular (LV) myocytes in heart/muscle-specific manganese-superoxide dismutase-deficient (H/M-Sod2 ^−/−) mice, which exhibit dilated cardiomyopathy due to increased oxidative stress. We also investigated the influences of intake of apple polyphenols (AP) containing mainly procyanidins with potent antioxidant activity. The QRS and QT intervals of ECG recorded in H/M-Sod2 ^−/− mice were prolonged. The effective refractory period in the LV myocardium of H/M-Sod2 ^−/− mice was prolonged, and susceptibility to ventricular tachycardia or fibrillation induced by rapid ventricular pacing was increased. Action potential duration in H/M-Sod2 ^−/− LV myocytes was prolonged, and automaticity was enhanced. The density of the inwardly rectifier K⁺ current (I K1) was decreased in the LV cells of H/M-Sod2 ^−/− mice. The AP intake partially improved these electrophysiological alterations and extended the lifespan in H/M-Sod2 ^−/− mice. Thus, chronic exposure of the heart to oxidative stress produces a variety of electrophysiological abnormalities, increased susceptibility to ventricular arrhythmias, and action potential changes associated with the reduced density of I K1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances.