In a canine model, sterile pericarditis induced a transmural gradient in connexins 40 and 43, which was associated with markedly abnormal atrial conduction and vulnerability to atrial arrhythmias.
In a canine model of sterile pericarditis, reduced and heterogeneously distributed connexins 40 and 43 correlate with abnormal atrial conduction and increased vulnerability to atrial arrhythmias.
The canine sterile pericarditis model is characterized by impaired conduction and atrial arrhythmia vulnerability. Electrical and structural remodeling processes caused by the inflammatory response likely promote these abnormalities. In the present study, we tested the hypothesis that altered distribution of atrial connexins is associated with markedly abnormal atrial conduction, thereby contributing to vulnerability to atrial flutter (AFL) and atrial fibrillation (AF) induction and maintenance. During rapid pacing and induced, sustained AFL or AF in five sterile pericarditis (SP) and five normal (NL) dogs, epicardial atrial electrograms were recorded simultaneously from both atria (380 electrodes) or from the right atrium (RA) and Bachmann's bundle (212 electrodes). Tissues from RA sites were subjected to immunostaining and immunoblotting to assess connexin (Cx) 40 and Cx43 distribution and expression. Transmural myocyte (alpha-actinin) and fibroblast (vimentin) volume were also assessed by immunostaining. RA pacing maps showed markedly abnormal conduction in SP, with uniform conduction in NL. Total RA activation time was significantly prolonged in SP vs. NL at 300-ms and 200-ms pacing-cycle lengths. Sustained arrhythmias were only inducible in SP total: 4/5 (AFL: 3/5; AF: 1/5). In NL, Cx40, Cx43, alpha-actinin, and vimentin were homogeneously distributed transmurally. In SP, Cx40, Cx43, and alpha-actinin were absent epicardially, decreased midmyocardially, and normal endocardially. SP increased epicardial vimentin expression, suggesting fibroblast proliferation. Immunoblot analysis confirmed reduced expression of Cx40 and Cx43 in SP. The transmural gradient in the volume fraction of Cx40 and Cx43 in SP is associated with markedly abnormal atrial conduction and is likely an important factor in the vulnerability to induction and maintenance of AFL/AF in SP.
Ryu et al. (Sat,) conducted a other in Sterile pericarditis and atrial arrhythmias (n=10). Sterile pericarditis model vs. Normal dogs was evaluated on Atrial conduction, arrhythmia inducibility, and connexin 40/43 distribution. In a canine model, sterile pericarditis induced a transmural gradient in connexins 40 and 43, which was associated with markedly abnormal atrial conduction and vulnerability to atrial arrhythmias.
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