Characterization of the Substrate in Atrial Fibrillation

心房颤动基质的表征

• 批准号: 7155940
• 负责人: SERGEY A VITEBSKIY
• 金额: $ 5.2万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155940
• 关键词: atrial fibrillation; cardiac myocytes; disease /disorder model; dogs; electrophysiology; endocardium; fibroblasts; gap junctions; heart conduction system; heart disorder; heart electrical activity; immunocytochemistry; membrane channels; pathologic process; pericardium; postdoctoral investigator

DESCRIPTION (provided by applicant): The goal is to use contemporary electrophysiologic and molecular techniques to characterize remodeling of the atrial substrate required for the establishment of sustained atrial fibrillation (AF) and flutter (AFL) in the canine sterile pericarditis model. Hypotheses to be tested include: # 1) a time course of atrial pathophysiologic changes (electrophysiologic and cellular) in response to pericarditis leads to development of (a) first inducibility of a reentrant circuit of very short cycle length that produces AF; later a line of functional block between the venae cavae which permits the development of AFL; and still later neither; all of which are related to alterations in the distribution and functional properties of cardiac gap junctions; (b) first a loss of connexins, then a loss of myocytes with their subsequent replacement by fibroblasts in the outer layers of the atrial myocardium, but no changes in the endocardial layer; (c) a decrease in the atrial epicardial wavelength associated with inducibility of AF or AFL; # 2) the endocardial atrial effective refractory period and conduction time will remain constant throughout the time course of the study. Data from the proposed studies will lead to an improved basis for prevention and treatment of AF and AFL.

描述（由申请人提供）：目标是利用当代电生理学和分子技术来表征在犬无菌性心包炎模型中建立持续性心房颤动（AF）和扑动（AFL）所需的心房基质的重塑。待测试的假设包括： # 1) 响应心包炎的心房病理生理学变化（电生理学和细胞学）的时间过程导致 (a) 产生 AF 的周期长度非常短的折返回路的首次诱导性；后来腔静脉之间出现一条功能阻滞线，允许 AFL 的发展；再后来也没有；所有这些都与心脏间隙连接的分布和功能特性的改变有关； (b) 首先损失连接蛋白，然后损失心肌细胞，随后被心房心肌外层的成纤维细胞取代，但心内膜层没有变化； (c) 与 AF 或 AFL 诱导相关的心房心外膜波长减小； # 2) 心房内膜有效不应期和传导时间在整个研究过程中保持恒定。拟议研究的数据将为 AF 和 AFL 的预防和治疗奠定基础。