Gap junction remodelling by chronic pressure overload is related to the increased susceptibility to atrial fibrillation in rat heart.
OBJECTIVE
Left atrial (LA) fibrosis caused by various pathological stimuli is a common finding. However, the difference of atrial remodelling via haemodynamic change in diverse cardiomyopathy has not been elucidated.


RESULTS
Male Sprague-Dawley rats (6-8 weeks, n = 180) were randomly assigned to three groups and corresponding sham control groups: (i) ischaemic cardiomyopathy, (ii) left ventricular hypertrophy (LVH), and (iii) dilated cardiomyopathy. At 12 weeks after operation, atrial fibrillation (AF) inducibility and duration were assessed by in vivo burst transoesophageal pacing. Using the Langendorff apparatus, left ventricular (LV) function and pressure were measured. The expression of connexin-43 (Cx43) and alpha-smooth muscle actin (α-SMA) in atrial tissues was assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining. Fibrosis was analysed by Masson's trichrome staining. Compared with controls, the LA weight/heart weight ratio was increased in the LVH group alone, and was significantly correlated with AF duration (P < 0.001, R = 0.388). Atrial fibrillation inducibility and duration were higher and longer only in the LVH group (P = 0.002, 0.079, respectively), and isolated LV diastolic dysfunction and elevated LV pressure were observed. Although α-SMA expression and fibrosis were increased in all three cardiomyopathy models, down-regulation of Cx43 expression in the LA was observed in the LVH group alone.


CONCLUSIONS
Chronic pressure overload in the absence of LV systolic dysfunction resulted in LA hypertrophy and increased susceptibility to AF, which might be related to conduction abnormality via decreased expression and lateral distribution of Cx43 as well as interstitial fibrosis.
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Seung Yong
SY
Shin
Department of Thoracic & Cardiovascular Surgery, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
Won-Min
WM
Jo
Department of Pain & Anesthesiology, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
Too Jae
TJ
Min
Department of Laboratory Medicine and Pathology, the Armed Forces Capital Hospital, Seongnam, Korea.
Byoung-Kwon
BK
Kim
Department of Pathology, Gyeongsang National University Hospital, Jinju, Korea.
Dae Hyun
DH
Song
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Seong Hyeop
SH
Hyeon
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Jee Eun
JE
Kwon
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Wang-Soo
WS
Lee
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Kwang Je
KJ
Lee
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Sang-Wook
SW
Kim
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Tae Ho
TH
Kim
Cardiovascular & Arrhythmia Center, Heart Research Institute, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.
Chee Jeong
CJ
Kim
Division of Cardiology, Department of Internal Medicine, Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, 80, Guro-2-dong, Guro-gu, Seoul 152-703, Korea.
Sung Il
SI
Im
Division of Cardiology, Department of Internal Medicine, Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, 80, Guro-2-dong, Guro-gu, Seoul 152-703, Korea hongeuy@korea.ac.kr h3lim@medimail.co.kr.
Hong Euy
HE
Lim
D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000150:complications / Q000503:physiopathology*; D002908:Chronic Disease; D017630:Connexins / Q000378:metabolism*; D004198:Disease Susceptibility; D017629:Gap Junctions / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D017630:Connexins
Atrial fibrillation; Connexin; Fibroblast; Fibrosis; Gap junction; Hypertrophy; Pressure overload; Remodelling