title: Progression of ventricular remodeling and arrhythmia in the primary hyperoxidative state of glutathione-depleted rats.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  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.
authors.affiliation: Department of Cardio-Angiology, Kitasato University School of Medicine, Sagamihara, Japan. ksayaka@med.kitasato-u.ac.jp
authors.forename: Sayaka
authors.initials: S
authors.lastname: Kurokawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Niwano
authors.forename: Hiroe
authors.initials: H
authors.lastname: Niwano
authors.forename: Shoko
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Kishihara
authors.forename: Yuya
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kosukegawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Masaki
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D001794:Blood Pressure; D015153:Blotting, Western; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002304:Cardiac Pacing, Artificial; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007150:Immunohistochemistry; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D018754:Ventricular Dysfunction; D020257:Ventricular Remodeling
chemical_list: C506948:Atp2a2 protein, rat; D016207:Cytokines; D051638:Ether-A-Go-Go Potassium Channels; C496886:Kcnh1 protein, rat; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D020097:Natriuretic Peptide, Brain; D019328:Buthionine Sulfoximine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D003849:Deoxyguanosine; D005978:Glutathione