ELECTRICAL REMODELING IN ATRIAL FIBRILLATION

心房颤动的电重构

• 批准号: 6056100
• 负责人: Jeffrey E Olgin
• 金额: $ 11.83万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6056100
• 关键词: atrial fibrillation; atrium; autoradiography; calcium flux; calcium indicator; disease /disorder proneness /risk; dogs; electrophysiology; gap junctions; heart electrical activity; heart innervation; immunocytochemistry

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.

心房颤动 (AF) 是美国最常见的心律失常 有证据表明，房颤期间的快速发生率会产生变化， 增加房颤本身的风险。然而，导致的机制 对阵发性至慢性 AF（“电重塑”）的了解甚少。 拟议的项目试图确定神经、离子、 这种自我延续的电生理学和结构机制 (AF) 的性质。申请人计划测试以下假设： 自主神经支配和细胞的异质分布 心房上的连接是房颤发作的原因；并作为 这些阵发的频率增加，慢性细胞内钙 发生过载，导致永久性细胞损伤，导致 下坡级联导致慢性房颤。期间的各个阶段 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 AF 诱导性和组织的电生理测量； 2）绘制副交感神经和交感神经支配的分布图 使用放射自显影术； 3) 使用荧光测量细胞内钙 染料； 4) 使用以下方法绘制心房中的细胞连接（间隙连接） 免疫组织化学； 5) 识别结构和细胞 心房异常。