[Association between myocardial connexin 40 and 45 expression and myocardial fibrosis in the rapid atrial pacing canine model].

OBJECTIVE

Electrical and structural remodeling are of importance for the occurrence and maintenance of atrial fibrillation. We observed association between atrial connexin protein expression and fibrosis in a canine model of prolonged rapid atrial pacing.

METHODS

"J"-type electrodes were placed in the right atrial appendage under the guidance of X-ray in 16 dogs, Animals in model group (n = 8) received fast pacing (400 beats/min) for 10 weeks while animals in control group (n = 8) maintained at sinus rhythm. Limb-lead ECGs were recorded at 2, 4, 6, 8 weeks respectively. Burst stimulation was applied to induce atrial fibrillation in all animals after 10 weeks, animals were sacrificed thereafter and the left atrial tissues were taken for myocardial collagen measurement (Masson staining) and myocardial ultrastructure examination and detection of protein expression of connexin (Cx) 40 and 45 (immune staining). Procollagen type III N-terminal peptide and type IV collagen in serum were also detected by radioimmunoassay.

RESULTS

Two dogs died in model group due to atrial rupture induced cardiac tamponade or lung emboli. Spontaneously atrial fibrillation was not observed in all animals, but two dogs developed atrial flutter and atrial premature beats. Atrial fibrillation was induced by burst stimulation in 4 out of 6 dogs in model group and in none of the dogs in control group. Atrial myocardial collagen volume fraction was significantly increased in model group compared with the control group (P < 0.05). Ultrastructure examination in atrial tissue evidenced disorder, fracture, collagen fiber proliferation, mitochondrial swelling, blurred cristae, and intercalated disc distortion, expansion, part of gap junction disappears in model group. The serum levels of procollagen type III N-terminal peptide and type IV collagen in model group were significantly higher than in the control group (P < 0.05). The protein expression of Cx 40 in atrial myocardium in model group was significantly higher than in control group (P < 0.05), while Cx 45 protein expression was similar between two groups (P > 0.05). The left atrial CVF was positively correlated with Cx 40 (r = 0.671, P < 0.01).

CONCLUSION

Increased myocardial fibrosis is positively correlated with upregulation of myocardial Cx 40 protein expression in left atrium in rapid atrial paced canine.