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

Authors: Tadahiro Sunagawa; Takahiko Shimizu; Akio Matsumoto; Motoyuki Tagashira; Tomomasa Kanda; Takuji Shirasawa; Haruaki Nakaya;

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

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 (IK1) 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 ofIK1. Dietary intake of antioxidant nutrients may prevent oxidative stress-induced electrophysiological disturbances.

Keywords

Cardiomyopathy, Dilated, Male, Mice, Knockout, Superoxide Dismutase, Myocardium, Polyphenols, Antioxidants, Electrophysiological Phenomena, Mice, Oxidative Stress, Dietary Supplements, Animals, Female, Myocytes, Cardiac, Research Article

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
15
Top 10%
Average
Average
Green
gold