RECEPTOR BASIS FOR MULTICENTRIC ORIGIN OF ATRIAL IMPULSE

与传统的单灶性窦优势描述不同， 结电发生，已经表明心房冲动起源开始于 多中心地从几个相距很远的地点包围一个地区 右心房45 x 15 mm 此外，每个单独的起搏器部位 与导致动态切换的不同速率上限相关联 与周期变化一致的心房起搏器（APM）之间 长度或速率。 这项研究的长期目标是了解 心房起搏复合体的基本机制， 这些观察的人。具体的目的是：1）歧视 在实际的多中心脉冲起源（MCO）和单个 形成模拟MCO的脉冲; 2）定量并明确MCO的作用机理; 多个APM的速率差异; 3）确定机制 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 并将该数据与实验获得的数据进行比较 在狗身上。 这些目标需要一个多学科的方法， 关于心房细胞外电位（ECP）的记录， 点在体内和体外。 心率和P波形态将 注意，心房激动序列和电位分布图将 在控制条件下和从 自主神经紊乱（药物输注和/或神经 STIYLAND）。 隔离、灌注的右心房准备将 需要确定药物输注对 APM复合体。 剂量反应数据将与APM位置相关。 的 输注研究和放射性配体结合分析将在 心房变时性受体机制的阐明。 获得的结果 从ECP将需要与潜在的相关性， 细胞内水平。 活化顺序和电位分布数据 将在心脏手术时从人体心脏中获取;数据 将在周期长度和启动的自发变化期间收集 条件以及变时性活动性心脏 给药。 这些研究将为以下方面提供新的基础： 了解心房率和节律的控制， 某些复杂的正常和异常的节奏，其特征是交替的 长周期和短周期序列，洞察房性心动过缓， 某些异位快速性心律失常，以及P波变化的基础 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.