RECEPTOR BASIS FOR MULTICENTRIC ORIGIN OF ATRIAL IMPULSE

与传统的对优势单灶性窦的描述不同 结节电发生，已证明心房冲动起源始于 多中心地从围绕一个区域的几个相隔很远的地点 右心房45x15 mm。此外，每个单独的起搏器位置都是 与导致动态切换的不同速率上限相关联 房性起搏器(APM)之间与周期变化一致 长度或速率。这项研究的长期主旨是理解 心房起搏器复合体的基本机制及其延伸 这些对人类的观察。具体目的是：1)歧视 在实际的多中心脉冲起源(MCO)和单中心脉冲传导之间 形成的冲量模拟MCO；2)定量定义了MCO的形成机理 多个APM的速率差异；3)确定机理 负责协调和控制多个和广泛的 分布式APM组件；4)定义APM的位置和功能 并将此数据与实验获得的数据进行比较 在狗身上。这些目标需要一个以多学科为中心的方法 关于记录高达360的心房细胞外电位(ECP) 分体内和体外两个方面。心率和P波形态将是 注意和心房激动序列和潜在分布图将 在控制条件下和在由 自主神经紊乱(药物输注和/或神经 刺激)。隔离、灌流的右房准备将是 有必要确定药物输注的直接影响 APM复合体。剂量-反应数据将与APM的位置相关。这个 输液研究和放射性核素结合分析将针对 心房变色受体机制的阐明。取得的成果 来自ECP的数据将需要与 细胞内水平。激活序列和潜在分布数据 将在心脏手术时从人类心脏获得；数据 将在周期长度和启动的自发变化期间收集 心脏起搏前、后的状态及变化 药物是用来管理的。这些研究应该提供一个新的基础 了解心房率和心律的控制，心绞痛的发生机制 某些复杂的正常和异常节律，以交替为特征 长和短周期序列，对房性缓慢性心律失常的洞察和 某些异位快速性心律失常及其P波改变的基础 体表心电图。

In contrast to the conventional description of predominant unifocal sinus node electrogenesis, it has been shown that atrial impulse origin begins multicentrically from several widely separated sites encompassing an area of 45 x 15 mm in the right atrium. Also, each separate pacemaker site is associated with a different upper rate limit resulting in dynamic switching between the atrial pacemakers (APMs) coincident with changes in cycle length or rate. The long-term thrust of this study is to understand the basic mechanisms underlying the atrial pacemaker complex and to extend these observations to man. The specific aims are to: 1) discriminate between actual multicentric impulse origin (MCO) and conduction of a singly formed impulse simulating MCO; 2) quantitate and define the mechanism of rate differences of the multiple APMs; 3) determine the mechanisms responsible for the coordination and control of the multiple and widely distributed APM components; 4) define the locations and functions of APMs in human subjects and compare this data with that obtained experimentally in dogs. These objectives necessitate a multidisciplined approach centered about the recording of atrial extracellular potentials (ECP) from up to 360 points in vivo and in vitro. HEART RATE AND P-WAVE MORPHOLOGY WILL BE NOTED AND ATRIAL ACTIVATION SEQUENCE AND POTENTIAL DISTRIBUTION MAPS WILL BE GENERATED DURING CONTROL CONDITIONS AND DURING CONDITIONS RESULTING FROM AUTONOMIC PERTURBATIONS (PHARMACOLOGIC INFUSIONS AND/OR NERVE STIMULATION). THE ISOLATED, PERFUSED RIGHT ATRIAL PREPARATION WILL BE NECESSARY TO DETERMINE THE DIRECT EFFECTS OF PHARMACOLOGIC INFUSIONS ON THE APM COMPLEX. DOSE-RESPONSE DATA WILL BE CORRELATED WITH APM LOCATION. THE INFUSION STUDIES AND RADIOLIGAND BINDING ANALYSES WILL BE DIRECTED AT THE ELUCIDATION OF ATRIAL CHRONOTROPIC RECEPTOR MECHANISMS. RESULTS OBTAINED FROM THE ECP WILL REQUIRE CORRELATIONS TO BE MADE WITH POTENTIALS AT THE INTRACELLULAR LEVEL. ACTIVATION SEQUENCE AND POTENTIAL DISTRIBUTION DATA WILL BE OBTAINED FROM THE HUMAN HEART AT THE TIME OF CARDIAC SURGERY; DATA WILL BE COLLECTED DURING SPONTANEOUS CHANGES IN CYCLE LENGTH AND INITIATING CONDITIONS AS WELL AS BEFORE AND AFTER CHRONOTROPICALLY ACTIVE CARDIAC DRUGS ARE ADMINISTERED. These studies should provide a new basis for understanding the control of atrial rate and rhythm, the mechanisms of certain complex normal and abnormal rhythms characterized by alternating long and short cycle sequences, insight into atrial bradyarrhythmias and certain ectopic tachyarrhythmias, and the basis for changes in the P wave of the surface ECG.