Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Heart Failure
Progression of Ventricular Remodeling and Arrhythmia in the Primary Hyperoxidative State of Glutathione-Depleted Rats
Sayaka KurokawaShinichi NiwanoHiroe NiwanoShoko IshikawaJun KishiharaYuya AoyamaTomoko KosukegawaYoshihiko MasakiTohru Izumi
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2011 Volume 75 Issue 6 Pages 1386-1393


Background: Although oxidative stress is considered to promote arrhythmogenic substrates in diseased model animals, it is difficult to evaluate its primary role. In this study, we evaluated the promotion of arrhythmogenic substrates in the primary hyperoxidative state. Methods and Results: Sprague-Dawley rats were treated with L-buthionine-sulfoximine (BSO, 30mmol·L-1·day-1) for 14 days. On day 7 or 14, the serum levels of derivatives of reactive oxygen metabolites (d-ROM) were measured, and immune staining of 8-hydroxy-2'-deoxyguanosine (8OHdG) was performed to assess oxidative stress. The ventricular effective refractory period (ERP), monophasic action potential duration (MAPD), and the inducibility of ventricular arrhythmia were also evaluated. BSO rats exhibited higher serum d-ROM and clearer 8OHdG staining than the controls. The inducibility of ventricular arrhythmia was higher in the BSO rats than in the controls. The ERP was shorter in the BSO rats than the control (day 14, 32±1 vs. 36±1ms, P<0.05), whereas the MAPD90 was longer in the BSO rats (day 14, 76±5 vs. 55±4ms, P<0.05). The mRNA levels of Kv4.2, erg, and SERCA2a were downregulated in the BSO rats (P<0.05), and Western blot analysis exhibited the downregulation of erg and SERCA2 expression in the BSO rats (P<0.05). Conclusions: Systemic oxidative stress might be one of the primary factors promoting cardiac electrophysiological remodeling and increasing the inducibility of arrhythmia independently of major organ disorders. (Circ J 2011; 75: 1386-1393)

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