Role of Stretch in Focal Atrial Fibrilation

描述(由申请人提供)： 应聘者希望从事心脏电生理学方面的学术和研究事业，主要专注于动物模型中房性心律失常的病理生理学。他在过去两年中的一年里(在临床心脏电生理学方面)致力于动物实验室，并在了解肺静脉的电生理学及其在房颤(AF)发生中的作用方面已经做了大量的工作。更好地了解房颤的潜在机制对于开发有效的预防和治疗这种心律失常的策略至关重要。最近的观察表明，在大量患者中，房颤可能起源于肺静脉的局灶性“触发器”。然而，这些焦点源的电生理特性并不是很清楚。在高分辨率光学标测的帮助下，候选者最近描述了肺静脉内的异质传导和复极，并展示了该区域的微小折返。 本项目旨在进一步表征犬肺静脉的电生理特性，以响应急性或慢性心房牵拉。预计这一指导奖将允许候选人发展分析以及技术和方法技能，他需要发展成为一名独立的内科科学家。候选人的导师在基础和临床心律失常研究方面有着开创性研究的长期记录；此外，Krannert研究所的动物研究设施是世界上最好的之一。 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。高密度心内膜导管标测(在完好的狗身上)和高分辨率光学标测(在朗宁多夫制剂中)将被用于研究肺静脉。在具体目标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。为此，将使用犬慢性二尖瓣反流模型。光学标测将在兰登多夫制剂中进行，以确定完整静脉的电生理。作为这一目标的一部分，还将进行组织学和缝隙连接研究。此外，我们还将研究分离的肺静脉心肌细胞的电生理学。

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.