Elevated oxidative stress is associated with ventricular fibrillation episodes in patients with Brugada-type electrocardiogram without SCN5A mutation.
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.
Tanaka
Masamichi
M
Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Nakamura
Kazufumi
K
Kusano
Kengo Fukushima
KF
Morita
Hiroshi
H
Ohta-Ogo
Keiko
K
Miura
Daiji
D
Miura
Aya
A
Nakagawa
Koji
K
Tada
Takeshi
T
Murakami
Masato
M
Nishii
Nobuhiro
N
Nagase
Satoshi
S
Hata
Yoshiki
Y
Kohno
Kunihisa
K
Ouchida
Mamoru
M
Shimizu
Kenji
K
Yutani
Chikao
C
Ohe
Tohru
T
Ito
Hiroshi
H
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
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