ATRIAL PACEMAKER COMPLEX - ATRIAL FLUTTER & FIBRILLATION

长期的目标是解释异常之间的联系 心房起搏器复合体(APMC)和心房扑动(AFL)的手术 和纤颤(AFB)。这项修订建议的具体目的是 确定自发性引发和终止的机制 房性折返性心动过速。这个实验室之前的工作表明 正常的房性心律是由一个多个、广泛的 分布式起搏器。通常，这些分布的起搏器区域是 功能集成，要么同步点火，要么由一个站点主导 并且随着速率的变化而使其他的去极化。初步观察 提示APMC在心肌梗死中既有促心律失常的作用，又有抗心律失常的作用。 折返性房性心动过速的自发启动和终止。 证据表明，在乙酰胆碱抑制胆碱能的过程中 ACh输注或迷走神经刺激，APMC可去极化 不同步的，导致一系列紧密耦合的去极化 类似于人工可编程刺激器，自发地启动 重返大气层。这项研究旨在揭示其潜在的机制。 用于APMC的异步转义，并定义已更改的 构成原则的激活和恢复的条件 固有底物(对异步的易损性增强 去极化)导致重返大气层。此外，这项研究将检查 这些不同因素之间的具体交互作用是 对AFL和AFB的自发发展至关重要。研究将会是 在(体外)隔离的、灌流的右房过载中进行 导致持续的AFL或AFB。三维贴身 电极模具将被用来记录来自不规则的电势 心房的心外膜和心内膜表面。单极和双极 将同时记录250到500个地点的心电记录，并 将制作计算机生成的激活和恢复地图 自动的。将对数据进行分析，以确定响应模式 以及心房起搏器不协调逃逸的机制。网站： 导致再入的单向传导阻滞将与 在长周期长度下通过正交起搏和通过 与采收率分布图进行比较。折返性阻塞部位 波前将与过早逃逸的位置和时间有关 对心房起搏器的恢复、时空变化、变化 在ERP分布上，与起搏部位呈方向性依赖。 来自实验犬类研究的信息将链接到 黄曲霉毒素和黄曲霉毒素的自发启动和终止机制 人类通过在心脏手术期间对患有这些疾病的患者进行研究 心律不齐。这些研究的结果应该具有重要的意义 对于外科、电气和药理学方法的设计：1) APMC的异步去极化控制，2)对APMC的修改 防止单向阻塞的脉冲传播路径；3) 恢复到心房的同质性复极。

The long-range objective is to explain the connection between abnormal operation of the atrial pacemaker complex (APMC) and atrial flutter (AFL) and fibrillation (AFB). The specific aim of this revised proposal is to determine the mechanisms of spontaneous initiation and termination of atrial reentry tachycardias. Previous work from this laboratory has shown that normal atrial rhythm is controlled by a system of multiple, widely distributed pacemakers. Normally, these distributed pacemaker regions are functionally integrated and either fire synchronously or one site dominates and depolarizes the others as rate changes. Preliminary observations indicate that the APMC plays both pro- and antiarrhythmic roles in the spontaneous initiation and termination of reentrant atrial tachycardias. Evidence indicates that during cholinergic suppression by acetylcholine (ACH) infusion or vagal stimulation, the APMC can depolarize asynchronously, resulting in a series of closely coupled depolarizations similar to an artificial programmable stimulator, spontaneously initiating reentry. This study has been designed to reveal the underlying mechanisms for the asynchronous escape of the APMC and also to define the altered conditions of activation and recovery which comprise the principle intrinsic substrates (of the enhanced vulnerability to asynchronous depolarizations) leading to reentry. In addition, the study will examine the specific interactions between these different factors which are essential to the spontaneous development of AFL and AFB. Studies will be performed in an (in vitro) isolated, perfused right atrial overload that results in either sustained AFL or AFB. Three-dimensional form-fitting electrode molds will be used to record potentials from the irregular epicardial and endocardial surfaces of the atria. Unipolar and bipolar electrograms will be recorded from 250 to 500 sites simultaneously and computer-generated maps of activation and recovery will be produced automatically. Data will be analyzed to determine the response patterns and mechanisms of uncoordinated escape of the atrial pacemakers. Sites of unidirectional conduction block resulting in reentry will be related to fiber orientation by orthogonal pacing at long cycle lengths and by comparison with maps of recovery distribution. Sites of block of reentrant wavefronts will be related to the location and timing of premature escapes of the atrial pacemakers, spatial and temporal changes in recovery, changes in ERP distribution, and paced sites of directionally dependent block. Information derived from experimental canine studies will be linked to mechanisms of spontaneous initiation and termination of AFL and AFB in humans, through studies during cardiac surgery in patients with these arrhythmias. Results of these studies should have important implications for design of surgical, electrical, and pharmacologic approaches to: 1) the control of asynchronous depolarization of the APMC, 2) modification of routes of impulse propagation to prevent unidirectional block, and 3) restoration of homogenous repolarization to the atria.