Characterization of the Substrate in Atrial Fibrillation

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构。有待检验的假说包括：#1)心包炎引起的心房病理生理变化(电生理和细胞)的时间进程导致：(A)首先可诱导非常短的周期长度的折返性回路产生房颤；然后是腔静脉之间的一条功能性阻滞线，使AFL得以发展；再后来两者都不是；所有这些都与心脏缝隙连接的分布和功能特性的变化有关；(B)首先是连接蛋白的丢失，然后是心肌细胞的丢失，随后是心房心肌外层的成纤维细胞替代它们，但心内膜层没有变化；(C)心房心外膜波长的减少与房颤或房颤的诱发性有关；#2)心内膜心房有效不应期和传导时间在整个研究过程中将保持不变。拟议研究的数据将为房颤和AFL的预防和治疗提供更好的基础。

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.