ATRIAL PACEMAKER COMPLEX--ATRIAL FLUTTER & FIBRILLATION

长期目标是解释异常的 心房起搏复合体（APMC）和心房扑动（AFL）的手术 和纤维性颤动（AFB）。 这项修订建议的具体目的是 确定自发启动和终止的机制 心房折返性心动过速 这个实验室以前的工作表明， 正常的心房节律是由一个系统控制的， 分布式起搏器。 正常情况下，这些分布的起搏器区域 功能集成，或者同步发射，或者一个站点占主导地位 并随着速率的变化使其它的去极化。 初步意见 表明，APMC发挥亲和抗肿瘤作用， 折返性房性心动过速的自发开始和终止。 有证据表明，在乙酰胆碱抑制胆碱能期间， (ACH)输注或迷走神经刺激，APMC可以去血管化， 不同步，导致一系列紧密耦合的去极化 类似于人工可编程刺激器， 再入 这项研究旨在揭示潜在的机制， 对于APMC的异步转义，也可以定义修改后的 激活和恢复的条件，包括以下原则 内在的基板（增强脆弱性异步 去极化）导致再入。 此外，该研究还将审查 这些不同因素之间的特定相互作用， 对AFL和AFB的自发发展至关重要。 研究将 在（体外）隔离的灌注右心房超负荷中进行， 导致持续性AFL或AFB。 三维适形 电极模具将被用来记录电位从不规则 心房的心外膜和内膜表面。 单极和双极 将同时记录250至500个部位的电描记图， 将制作计算机生成的激活和恢复图 的自动 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。 位点 导致折返的单向传导阻滞将与 通过长周期长度的正交起搏和 与恢复分布图的比较。 折返块部位 波前将与过早逃逸的位置和时间有关 的心房起搏器，空间和时间的变化，恢复，变化 在ERP分布中，方向依赖性阻滞的起搏部位。 来自实验犬研究的信息将与 AFL和AFB自发发生和终止的机制 人类，通过对这些患者心脏手术期间的研究， 心律不齐 这些研究的结果应该具有重要的意义 用于设计手术、电气和药理学方法，以：1） 控制APMC的异步去极化，2）修改 脉冲传播的路径，以防止单向阻塞，以及3） 恢复心房的均匀复极化。

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.