8-hydroxy-2--deoxyguanosine and Ventricular-Dysfunction

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.. Sprague-Dawley rats were treated with L-buthionine-sulfoximine (BSO, 30 mmol · 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 (8O HdG) 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 ± 1 ms, P<0.05), whereas the MAPD(90) was longer in the BSO rats (day 14, 76 ± 5 vs. 55 ± 4 ms, 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).. 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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Action Potentials; Analysis of Variance; Animals; Arrhythmias, Cardiac; Blood Pressure; Blotting, Western; Buthionine Sulfoximine; Cardiac Pacing, Artificial; Cytokines; Deoxyguanosine; Disease Models, Animal; Disease Progression; Ether-A-Go-Go Potassium Channels; Glutathione; Hydrogen Peroxide; Immunohistochemistry; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Shal Potassium Channels; Time Factors; Ventricular Dysfunction; Ventricular Remodeling