ATRIAL FIBRILLATION AND FLUTTER IN A MODEL

本研究计划有两个长期目标：1）使用 电生理学和药理学技术，以改善我们的 了解心房颤动的机制， 心房扑动，和2）发展一个更好的基础，为他们的治疗。 研究计划的具体目标是：（1）确定 一种新的犬无菌性心包炎模型中的心房颤动 关于其发生（诱导）、维持、终止 （自发或药物诱导）和预防（通过药物或 选择的病变）; 2）表征心房和心房肌之间的相互关系， 无菌心包炎模型中的房扑和房颤;以及3） 基于我们之前对无菌性心包炎心房扑动的研究， 模型，以便我们更好地了解其功能的组成部分， 确定的可重入回路，特别是可兴奋间隙， 慢传导，以及循环波阵面的阻塞部位， 选定的干预措施。 核心假设是心房颤动 在无菌心包炎模型中， 短周期长度的心房游离壁折返回路（转子）， 驱动两个心房，围绕右心房游离壁迁移， 周期性消失和重组，而心房扑动是由 单个稳定的右心房游离壁转子。 所有其他假设都与 直接或间接地对这一主题，并包括一系列的假设 与每一个具体目标有关。 在这些心房中使用的方法 心律失常模型包括使用无菌手术来产生无菌的 心包炎犬模型;使用标准手术技术暴露 用于慢性无菌性心包炎模型中标测研究的心脏， 在正常心脏中;同时多点（多路复用）记录的使用 技术在各种电生理研究;使用 心脏起搏技术;标准药理学技术的使用 在所选药剂的给药期间;以及使用标准 微电极技术 该项目的健康相关性是明确的， 因为心房纤维性颤动和心房扑动都是众所周知， 临床上很麻烦，而且对节律知之甚少， 影响了大量患者。 拟议的研究应提供 重要的新信息，以帮助提高认识和治疗 这些心律失常的患者。

There are two long term objectives of this research plan; 1) to use electrophysiological and pharmacological techniques to improve our understanding of the mechanisms responsible for atrial fibrillation and atrial flutter, and 2) to develop an improved basis for their treatment. The specific aims of the research plan are 1) to identify the mechanism of atrial fibrillation in a newly described canine sterile pericarditis model with respect to its onset (induction), maintenance, termination (spontaneous or drug induced) and prevention (by drugs or creation of selected lesions); 2) to characterize the interrelationship between atrial flutter and atrial fibrillation in the sterile pericarditis model; and 3) to build on our previous studies of the sterile pericarditis atrial flutter model such that we better understand the components of its functionally determined reentrant circuit, especially the excitable gap, the areas of slow conduction, and the site of block of the circulating wave front during selected interventions. The central hypothesis is that atrial fibrillation in the sterile pericarditis model is generated by a single, unstable, right atrial free wall reentrant circuit (rotor) of short cycle length which drives both atria, migrates about the right atrial free wall, and cyclically disappears and reforms, whereas atrial flutter is generated by a single, stable right atrial free wall rotor. All other hypotheses relate directly or indirectly to this theme and include a series of hypotheses related to each of the specific aims. Methods to be used in these atrial arrhythmia models include the use of aseptic surgery to create the sterile pericarditis canine model; use of standard surgical techniques to expose the heart for mapping studies in the chronic sterile pericarditis model and in normal hearts; use of simultaneous multisite (multiplexing) recording techniques during the various electrophysiologic studies; the use of cardiac pacing techniques; the use of standard pharmacological techniques during the administration of selected agents; and the use of standard microelectrode techniques. The health relatedness of the project is clear, in that both atrial fibrillation and atrial flutter are well known, clinically troublesome, and poorly understood rhythms which adversely affect large numbers of patients. The proposed studies should provide important new information to assist in improved understanding and treatment of patients suffering from these rhythm disorders.