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Relationship Between Connexins and Atrial Activation During Human Atrial Fibrillation
Author(s) -
KANAGARATNAM PRAPA,
CHERIAN ASHOK,
STANBRIDGE REX D.L.,
GLENVILLE BRIAN,
SEVERS NICHOLAS J.,
PETERS NICHOLAS S.
Publication year - 2004
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2004.03280.x
Subject(s) - connexin , atrial fibrillation , medicine , sinus rhythm , cardiology , gap junction , electrical conduction system of the heart , fibrillation , electrocardiography , microbiology and biotechnology , intracellular , biology
Gap junctional connexin proteins (connexin40 [Cx40], connexin43 [Cx43]) are a determinant of myocardial conduction and are implicated in the development of atrial fibrillation (AF). We hypothesized that atrial activation pattern during AF is related to connexin expression and that this relationship is altered by AF‐induced remodeling in the fibrillating atria of chronic AF. Methods and Results: Isochronal activation mapping was performed during cardiac surgery on the right atria of patients in chronic AF (n = 13) using an epicardial electrode array. The atrial activation pattern was categorized using a complexity score based on the number of propagating wavefronts of activation and by grouping atria into those capable of uniform planar activation (simple) and those that were not (complex). The activation pattern was correlated with the levels of Cx43 and Cx40 signal measured by immunoconfocal quantification of biopsies from the mapped region. We studied the impact of electrical remodeling by comparing these findings with the unremodeled atria of patients in sinus rhythm during pacing‐induced sustained AF (n = 17). In chronic AF, atria with complex activation had lower Cx40 signal than atria showing simple activation (0.013 ± 0.006 μ m 2 / μ m 2 vs 0.027 ± 0.009 μ m 2 / μ m 2 , P < 0.02), with the relative connexin signal (Cx40/Cx40 + Cx43) correlating with complexity score (P = 0.01, r = − 0.74). This relationship did not occur in the unremodeled atria, and increased heterogeneity of distribution of Cx40 labeling in chronic AF was the only evidence of connexin remodeling that we detected in the overall group. Conclusion: The pattern of atrial activation is related to immunoconfocal connexin signal only in the fully remodeled atria of chronic AF. This suggests that intercellular coupling and pattern of atrial activation are interrelated, but only in conjunction with the remodeling of atrial electrophysiology that occurs in chronic AF. (J Cardiovasc Electrophysiol, Vol. 15, pp. 206‐213, February 2004)