The Correlations Between Connexin Protein And Myocardial Fibrosis In Rapid Atrial Pacing Canine Model Of Atrial Fibrillation

Objective:Electrical remodeling and structural remodeling has relation to the occurrence and maintenance mechanism of atrial fibrillation.Connexin is an important component of myocardial intercalated disc,which is the metabolic coupling and electrical coupling between myocardial cells,and the structural basis for electrophysiological beat. Remodeling of connexin protein can affect the polarity of electrical conduction in myocardial cells,there conduction block or reentry triggered arrhythmias.Datum show that there were different degrees of change with connexin protein in patients with atrial fibrillation,suggesting that changes in connexin protein may be related to the occurrence of atrial fibrillation.We shall establish the atrial fibrillation model by rapid atrial pacing in canine,observe the changes of connexin protein and myocardial fibrosis in atrium,and analyze the relationship between them.Methods:16 dogs were randomly divided into two groups:model group and control group.All the dogs were placed "J"-type electrode in the right atrial appendage under X-ray.The dogs in model group are to be fast 400bpm pacing,while the dogs in control group are to maintain sinus rhythm.Continuous pacing for 10 weeks,limb-lead ECG are tested in 2,4,6,8 weeks respectively.The dogs which do not appear atrial fibrillation after 10 weeks will be induced by burst stimulation for atrial fibrillation.The dogs will be killed in the end of study,and the left atrial tissues will be obtained for myocardial tissue slice preparation.The changes of myocardial collagen in left atrial are observed by Masson staining.Myocardial ultrastructure and the intercalated disk are observed by electron microscopy.Procollagen type III-terminal peptide and type IV collagen in serum were detected by radioimmunoassay;Expression of Connexin 43,connexin 40 and connexin 45 in left atrium are detected by immune staining.Results:The dogs in model group did not appear atrial fibrillation spontaneously,but two dogs had appeared atrial flutter and atrial premature beats.All the dogs were stimulated by burst stimulation. 4 dogs in model group appear atrial fibrillation in the end.Success rate of the model making was about 65%. Compared with the control group, atrial myocardial collagen volume fraction increased in model group (P <0.05), especially endocardial and interstitial fibrosis . Ultrastructure of myocardium can be seen disorder, fracture, collagen fiber proliferation, mitochondrial swelling, cristae blurred, and intercalated disc distortion, expansion, part of gap junction disappears in model group.The serum levels of PIIINP and CIV in model group were significantly higher than the control group(P <0.05).The expression of connexin 43 and connexin 40 protein in atrial myocardium increased in model group (P <0.05), while the change of connexin 45 protein was no significant(P> 0.05).The left atrial CVF were associated with connexin 43 and connexin 40 by line analysis,and the results showed that CVF was positively correlated to connexin 43 and connexin 40,and the correlation coefficient r were 0.668 and 0.671 respectively.Conclusions: Rapid atrial pacing-induced atrial fibrillation in canine is effective and feasible. Rapid atrial pacing in canine induced myocardial fibrosis in left atrium. Rapid atrial pacing in canine induced the expression of connexin 43 and connexin 40 increased in left atrium,but has no effect on connexin 45.The changes of connexin 43 and connexin 40 are affected by the degree of atrial myocardial fibrosis in rapid atrial pacing-induced atrial fibrillation in canine.