Gap Junction Remodelling by Chronic Pressure Overload Is Related to the Increased Susceptibility to Atrial Fibrillation in Rat Heart

Europace. 2015 Apr;17(4):655-63. doi: 10.1093/europace/euu294. Epub 2014 Nov 14.


Aims: 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.

Methods and 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.

Conclusion: 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.

Keywords: Atrial fibrillation; Connexin; Fibroblast; Fibrosis; Gap junction; Hypertrophy; Pressure overload; Remodelling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Fibrillation / physiopathology*
  • Blood Pressure
  • Cardiomyopathies / complications
  • Cardiomyopathies / physiopathology*
  • Chronic Disease
  • Connexins / metabolism*
  • Disease Susceptibility
  • Gap Junctions / metabolism*
  • Hypertrophy, Left Ventricular / complications
  • Hypertrophy, Left Ventricular / physiopathology*
  • Male
  • Rats
  • Rats, Sprague-Dawley


  • Connexins