Role of Stretch in Focal Atrial Fibrilation

描述（由申请人提供）： 候选人希望从事心脏电生理学的学术和研究事业，主要关注动物模型中房性心律失常的病理生理学。 他在过去两年的研究（临床心脏电生理学）中有一年致力于动物实验室，并且已经在了解肺静脉的电生理学及其在房颤（AF）发生中的作用方面做了大量工作。 更好地了解房颤的潜在机制对于制定有效的预防和治疗策略至关重要。 最近的观察表明，在大量患者中，AF可能起源于肺静脉中的局灶性“触发”。 然而，这些局灶性源的电生理特性定义不清。 在高分辨率光学标测的帮助下，该候选人最近描述了肺静脉内的不均匀传导和复极，并证明了该区域的微折返。 本项目旨在进一步表征犬肺静脉对急性或慢性心房牵张的电生理特性。 预计这个指导奖将允许候选人发展分析以及技术和方法技能，他需要发展成为一个独立的医生科学家。 候选人的导师在基础和临床心律失常研究方面具有开创性研究的长期记录;此外，Krannert研究所的动物研究设施也是世界上最好的。 具体目标1将尝试研究急性球囊拉伸/扩张对正常犬肺静脉电生理的影响。 将使用高密度内镜导管标测（在完整犬中）和高分辨率光学标测（在Langendorff制备中）研究肺静脉。 在特定目标2中，我们将检查慢性心房扩张背景下肺静脉的电生理特征。 慢性二尖瓣返流犬模型将用于此目的。 将在Landendorff准备中进行光学标测，以确定完整静脉中的电生理学。 组织学和间隙连接研究也将作为该目标的一部分进行。 此外，我们将研究离体肺静脉心肌细胞的电生理。

DESCRIPTION (provided by applicant): The candidate wishes to pursue an academic and research career in cardiac electrophysiology, with a primary focus on the pathophysiology of atrial arrhythmias in animal models. He has dedicated one of the last two years of his fellowship (in clinical cardiac electrophysiology) to the animal lab, and has already done considerable work in understanding the electrophysiology of the pulmonary veins and their role in the genesis of atrial fibrillation (AF). A better understanding of the underlying mechanisms of AF is crucial to the development of effective preventive and therapeutic strategies for this arrhythmia. Recent observations suggest that in a large number of patients, AF may be originating from focal "triggers" in the pulmonary veins. The electrophysiologic properties of these focal sources are poorly defined, however. With the aid of high-resolution optical mapping, the candidate has recently described heterogeneous conduction and repolarization within the pulmonary veins, and has demonstrated micro re-entry in this region. This project aims to further characterize the electrophysiologic properties of canine pulmonary veins, in response to acute or chronic atrial stretch. It is expected that this mentored award will allow the candidate to develop the analytical as well as the technical and methodological skills he requires to develop into an independent physician-scientist. The candidate's mentors have a long track record of pathbreaking investigation in basic and clinical arrhythmia research; in addition, the animal research facilities at the Krannert Institute are amongst the finest in the world. Specific Aim 1 will attempt to study the effects of acute balloon stretch/dilatation on the electrophysiology of normal, canine pulmonary veins. Both high-density endocardial catheter mapping (in the intact dog) and high-resolution optical mapping (in a Langendorff preparation) will be utilized to study the pulmonary veins. In Specific Aim 2, we will examine electrophysiologic characteristics of the pulmonary vein in the setting of chronic atrial dilatation. A canine model of chronic mitral regurgitation will be used for this purpose. Optical mapping will be performed in a Landendorff preparation to determine the electrophysiology in the intact vein. Histologic and gap junction studies will be also performed as part of this aim. In addition, we will study the electrophysiology of isolated pulmonary vein cardiomyocytes.