Characterization of the Substrate in Atrial Fibrillation

描述（由申请人提供）：目的是使用现代电生理学和分子技术来表征犬无菌心包炎模型中建立持续性心房颤动（AF）和扑动（AFL）所需的心房底物重构。有待检验的假设包括：1)心包炎引起的心房病理生理变化（电生理和细胞）的时间过程导致(a)首先诱导产生心房颤动的极短周期长度的重入回路；后来在腔静脉之间形成一条功能阻滞线，允许AFL的发展；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)首先是连接蛋白的缺失，然后是心肌细胞的缺失，随后由心房心肌外层的成纤维细胞取代，但心内膜没有变化；(c)心房心外膜波长减少与AF或AFL的诱发性相关；# 2)心内膜心房有效不应期和传导时间在整个研究过程中保持不变。拟议研究的数据将改善AF和AFL的预防和治疗基础。

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.