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. Methods: During rapid pacing and induced, sustained AFL or AF in 5 sterile pericarditis (SP) and 5 normal (NL) dogs, epicardial atrial electrograms were recorded simultaneously from both atria (380 electrodes) or the RA and Bachmann's bundle (212 electrodes). Tissues from RA sites were subjected to immunostaining and immunoblotting to assess Cx40 and Cx43 distribution and expression. Transmural myocyte (-actinin) and fibroblast (vimentin) volume was also assessed by immunostaining. Results: 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 (4/5 [AFL:3/5; AF:1/5]). In NL, Cx40, Cx43, -actinin and vimentin were homogeneously distributed transmurally. In SP, Cx40, Cx43 and -actinin were absent epicardially, decreased mid-myocardially and normal endocardially. SP increased epicardial vimentin expression,,suggesting fibroblast proliferation. Immunoblot analysis confirmed reduced expression of Cx40 and Cx43 in SP. Conclusion: 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.