Relationship between connexins and atrial activation during human atrial fibrillation
Relationship between connexins and atrial activation during human atrial fibrillation
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DOI：
10.1046/j.1540-8167.2004.03280.x
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发表时间：
2004-02-01
影响因子：
2.7
通讯作者：
Peters, NS
中科院分区：
文献类型：
--
作者：
Kanagaratnam, P;Cherian, A;Peters, NS
简介：缝隙连接连接蛋白(Cx40[Cx40]，Cx43[Cx43])是心肌传导的决定因素，与房颤的发生发展密切相关。我们假设房颤时的心房激活模式与连接蛋白的表达有关，这种关系可通过房颤诱导的心房颤动重构而改变。方法和结果：在心脏手术期间，使用心外膜电极阵列对13例慢性房颤患者的右心房进行等时激活标测。根据激活波阵面数目的复杂性评分对心房激动模式进行分类，并将心房分为能够均匀平面激动的(简单)和非平面激动的(复杂)。激活模式与免疫共聚焦定量标记区活检组织中Cx43和Cx40信号的水平相关。我们通过将这些发现与起搏诱发持续性房颤(n=17)期间窦性心律患者未重构的心房进行比较，研究了电重构的影响。在慢性房颤患者中，复杂激活的房颤的Cx40信号低于单纯激活的房颤(0.013+/-0.006 um(2)/um(2)vs 0.027+/-0.009 um(2)/um(2)，P<0.02)，其相对连接蛋白信号(Cx40/Cx40+Cx43)与复杂程度评分相关(P=0.01，r=-0.74)。这种关系在未重构的心房中不存在，Cx40标记在慢性房颤中分布的不均一性增加是我们在整个组中检测到的连接蛋白重构的唯一证据。结论：只有在慢性房颤完全重构的心房中，心房激活模式与免疫共聚焦连接蛋白信号有关。这表明细胞间耦合和心房激活模式是相互关联的，但仅与慢性房颤时发生的心房电生理重构有关。
Connexins in Atrial Fibrillation.Introduction: 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 mum(2)/mum(2) vs 0.027 +/- 0.009 mum(2)/mum(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.