Cardiac electrophysiological alterations in heart/muscle-specific manganese-superoxide dismutase-deficient mice: prevention by a dietary antioxidant polyphenol.

Tadahiro Sunagawa,Haruaki Nakaya,Takuji Shirasawa,Motoyuki Tagashira,Takahiko Shimizu,Akio Matsumoto,Tomomasa Kanda

doi:10.1155/2014/704291

Abstract

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.

Highlights

Cardiac arrhythmia is a major health problem in the elderly
Mice whose QT interval was unmeasurable because of overlapping of T wave and P wave were excluded from analysis
Heart/muscle-specific manganese-superoxide dismutasedeficient (H/M-Sod2−/−) mice showed shorter survival times compared to the control mice and the survival rate was improved by apple polyphenols (AP) intake (Figure 1(a)), which is consistent with our recent report [8]

Summary

Introduction

Cardiac arrhythmia is a major health problem in the elderly. The incidence of ventricular arrhythmias is higher in patients with heart disease, premature ventricular contractions (PVCs) and multiform PVCs are common even in healthy aged people [1,2,3]. Oxidative stress has been implicated in age-related changes in the electromechanical function of the heart. The generation of reactive oxygen species (ROS) and age-inherent loss in antioxidant capacity may be involved in age-related cardiac dysfunction [4,5,6]. We previously reported that heart/muscle-specific manganesesuperoxide dismutase- (Mn-SOD-) deficient (H/M-Sod2−/−) mice exhibited progressive congestive heart failure with the typical pathology of dilated cardiomyopathy [7]. Biochemical analyses using ROS-reacting reagents revealed that a lack of Mn-SOD induced ROS production in the cardiomyocytes of mutant mice in vivo [8].

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Conclusion