ELECTRICAL REMODELING IN ATRIAL FIBRILLATION

房颤(房颤)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产生的变化 增加房颤本身的风险。然而，导致这些问题的机制 阵发性房颤到慢性房颤(“电重构”)知之甚少。 拟议的项目试图确定神经、离子、 这种自我永续的电生理和结构机制 (房颤)的性质。申请者计划检验假设 植物神经支配和细胞的异质性分布 心房上的连接是房颤发作的原因； 这些阵发性发作的频率增加，慢性细胞内钙 发生过载，导致永久性细胞损伤，导致 下坡向慢性房颤发展。在不同的阶段 从阵发性房颤到慢性房颤的犬模型，我们计划1) 测定房颤诱发率和组织性的电生理指标； 2)绘制副交感神经和交感神经分布图 用放射自显影；3)用荧光法测量细胞内钙 染料；4)绘制心房中的细胞连接(缝隙连接)图 免疫组织化学；5)鉴定结构和细胞 心房的异常。

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.