ELECTRICAL REMODELING IN ATRIAL FIBRILLATION

心房颤动（AF）是美国最常见的心律失常。 有证据表明，房颤期间的快速心率会产生变化， 增加了AF本身的风险。然而，导致这些问题的机制 阵发性到慢性AF（“电重构”）的机制知之甚少。 拟议的项目试图确定神经，离子， 这种自我延续的电生理和结构机制 的性质（AF）。申请人计划检验以下假设： 自主神经分布不均匀， 心房上的连接是AF发作的原因; 这些发作的频率增加，慢性细胞内钙 发生过载，导致永久性细胞损伤，导致 慢性房颤的下行级联。在不同阶段， 我们计划在犬模型中从阵发性房颤转变为慢性房颤1） 确定房颤诱发和机化的电生理指标; 2)绘制副交感神经和交感神经分布图 使用放射自显影术; 3）使用荧光显微镜测量细胞内钙 染料; 4）绘制心房中的细胞连接（缝隙连接）， 免疫组织化学;和5）鉴定结构和细胞 心房异常

Atrial fibrillation (AF) is the most common arrhythmia in the U.S. Growing evidence suggests that the rapid rates during AF create changes which enhances the risk of AF itself. However, the mechanisms that lead from paroxysmal to chronic AF ("electrical remodeling") are poorly understood. The proposed project attempts to determine the neural, ionic, electrophysiologic and structural mechanism of this self-perpetuating nature of (AF). The applicant plans to test the hypothesize that heterogeneous distribution of autonomic innervation and cellular connections on the atria are responsible for paroxysms of AF; and as the frequency of these paroxysms increase, chronic intracellular calcium overload occurs, resulting in permanent cell damage, leading to the downhill cascade towards chronic AF. At various stages during the transition from paroxysmal to chronic AF in a canine model we plan to 1) determine electrophysiologic measures of AF inducibility and organization; 2) map the distribution of parasympathetic and sympathetic innervation using autoradiography; 3) measure intracellular calcium using fluorescent dyes; 4) map the cellular connections (gap junctions) in the atria using immunohistochemistry; and 5) identify structural and cellular abnormalities in the atria.