Characterization of the Substrate in Atrial Fibrillation

描述（由申请方提供）：目的是使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房颤（AF）和房扑（AFL）所需的心房基质重塑。待检验的假设包括：1）心房病理生理变化的时间过程（电生理和细胞的）反应心包炎导致发展（a）第一个非常短的周期长度的折返回路的诱导，产生AF;后来的腔静脉之间的功能阻滞线，允许发展AFL;再后来两者都没有;（B）首先是连接蛋白的损失，然后是肌细胞的损失，随后由心房心肌外层的成纤维细胞替代，但内膜层没有变化;（c）与AF或AFL的诱导相关的心房心外膜波长的减小;#2）在整个研究的时间过程中，心房内膜有效不应期和传导时间将保持恒定。拟议研究的数据将为预防和治疗AF和AFL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.