title: Elevated oxidative stress is associated with ventricular fibrillation episodes in patients with Brugada-type electrocardiogram without SCN5A mutation.
abstract: BACKGROUND
  Brugada syndrome is a disease known to cause ventricular fibrillation with a structurally normal heart and is linked to SCN5A gene mutation. However, the mechanism by which ventricular fibrillation develops in cases of Brugada-type electrocardiogram without SCN5A mutation has remained unclear. Recently, oxidative stress has been implicated in the pathophysiology of cardiac arrhythmia. We also investigated oxidative stress levels in the myocardia of patients with Brugada-type electrocardiogram.
  
  
  METHODS
  Endomyocardial biopsy samples were obtained from 68 patients with Brugada-type electrocardiogram (66 males and two females). We performed histological and immunohistochemical analyses for CD45, CD68, and 4-hydroxy-2-nonenal-modified protein, which is a major lipid peroxidation product.
  
  
  RESULTS
  SCN5A mutation was detected in 14 patients. Ventricular fibrillation was documented in three patients with SCN5A mutation and in 11 without SCN5A mutation. In patients with SCN5A mutation, 4-hydroxy-2-nonenal-modified protein-positive area was not significantly different between the documented ventricular fibrillation (VF) group (VF+ group) and the group without documented VF (VF- group). However, in patients without SCN5A, the area was significantly larger in the VF+ group than that in the VF- group (P<.05). All other parameters (fibrosis area, CD45, and CD68) were not different between the VF+ and VF- group in both SCN5A+ and SCN5A- patients.
  
  
  CONCLUSIONS
  Oxidative stress is elevated in the myocardium of patients with Brugada-type electrocardiogram who have VF episodes and do not have SCN5A gene mutations. Oxidative stress may be associated with the occurrence of VF in patients with Brugada-type electrocardiogram without SCN5A mutation.
authors.affiliation: Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kengo Fukushima
authors.initials: KF
authors.lastname: Kusano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohta-Ogo
authors.forename: Daiji
authors.initials: D
authors.lastname: Miura
authors.forename: Aya
authors.initials: A
authors.lastname: Miura
authors.forename: Koji
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tada
authors.forename: Masato
authors.initials: M
authors.lastname: Murakami
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishii
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagase
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Hata
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Kohno
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ouchida
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
authors.forename: Chikao
authors.initials: C
authors.lastname: Yutani
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001483:Base Sequence; D053840:Brugada Syndrome / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D004562:Electrocardiography; D004699:Endocardium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018384:Oxidative Stress; D015222:Sodium Channels / Q000235:genetics*; D014693:Ventricular Fibrillation / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D000097382:CD68 Molecule
chemical_list: D000447:Aldehydes; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017931:DNA Primers; D017493:Leukocyte Common Antigens; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C568320:SCN5A protein, human; C027576:4-hydroxy-2-nonenal