ORGANIZATION OF EXCITATION IN HUMAN ATRIAL FIBRILATION

人心房颤动的兴奋组织

• 批准号: 7921513
• 负责人: OMER BERENFELD
• 金额: $ 35.23万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7921513
• 关键词: Achievement; Acute; Adenosine; Animals; Area; Arrhythmia; Atrial Fibrillation; Award; Basic Science; Biophysics; Cardiac; Cell physiology; Chronic; Clinical; Clinical Research; Clinical Sciences; Collaborations; Communication; Complex; Computer Simulation; Consultations; Data; Dependency; Development; Distal; Electrophysiology (science); France; Frequencies; Funding Mechanisms; Hand; Heart; Heart Atrium; Human; Infusion procedures; Inpatients; Investments; Knowledge; Laboratories; Left atrial structure; Liquid substance; Location; Maintenance; Manuscripts; Maps; Measures; Modeling; Molecular; Morphology; Nature; Optics; Pathway interactions; Patients; Pattern; Publications; Recording of previous events; Research Personnel; Resolution; Resources; Right atrial structure; Science; Scientist; Signal Transduction; Site; Societies; Source; Sum; Supervision; Testing; Translating; Work; abstracting; appendage; base; computerized data processing; experience; heart rhythm; improved; indexing; intercellular communication; interest; mathematical model; member; peer; programs; research study; response; simulation; stem; success; working group

The mechanisms of human atrial fibrillation (AF) are poorly understood. Previous isolated animal heart experiments demonstrated that some cases of acute AF may be maintained by the uninterrupted periodic activity of a small number of discrete reentrant sites (rotors) located in the posterior LA wall, near the PV/LA junction. In those experiments, the fastest rotors acted as dominant frequency sources (drivers) that maintained the overall activity. This resulted in a hierarchy of local excitation frequencies throughout both atria. More recently, clinical studies have confirmed the existence of a hierarchical organization in the rate of activation of different regions in the atria of patients with paroxysmal and chronic atrial fibrillation. However, the mechanisms underlying such a hierarchical; distribution of frequencies in human AF has not been explored. Our general hypothesis is that both local activation frequency and degree of regularity, while different in different parts of the atrium, are distributed non-randomly, with different patterns of distribution in paroxysmal versus chronic AF patients. We further surmise that such patterns are the result of fibrillatory conduction of waves emanating from AF drivers localized at the site of highest frequency and organization activity, with a gradual reduction of activation frequency as the distance from the driver increases. Thus our Specific Aims are: 1. In patients with paroxysmal and chronic AF, to quantify online and with high resolution the dominant frequency (DF) and regularity index (Rl) of the endocardia! electrical signals as separate measures of rate and fragmentation, respectively. 2. Also in patients with paroxysmal and chronic AF, to differentiate between reentrant and focal AF drivers by studying the effects of adenosine infusion on the DF and Rl distributions. 3. In paroxysmal AF patients, to determine the "breakdown frequency" at which rapid pacing in the presence and the absence of adenosine results in wavefront fragmentation, reflected by a sudden change from 1:1 LA:RA activation to fibrillatory conduction. 4. In computer simulations, to study the mechanisms of initiation and maintenance of AF at the PV/LA junction using three different computer models with increasing anatomical complexity. Successful achievement of our specific aims should help us advance understanding of the mechanisms and manifestations of this complex arrhythmia and may help to directly improve the efficacy of pharmacological and ablative therapies in patients.

人心房颤动（AF）的机制知之甚少。以前的孤立动物心脏 实验表明，某些急性AF病例可能由不间断的周期性维持 位于PV/LA附近的LA后壁中的少数离散的rectrant位点（转子）的活动 交界处。在这些实验中，最快的转子充当了主要的频率来源（驱动程序） 保持整体活动。这导致了整个局部激发频率的层次结构 心房。最近，临床研究证实了一个分层组织的存在。 阵发性和慢性心房颤动患者心房中不同区域的激活。然而， 这种层次结构的基础机制；人AF中频率的分布尚未 探索。我们的总体假设是局部激活频率和规律性程度，而 中庭不同部位的不同部分是非随机分布的，具有不同的分布模式 阵发性与慢性AF患者。我们进一步推测，这种模式是原纤维的结果 从最高频率和组织位置的AF驱动器发出的波浪传导 活动，随着与驾驶员的距离的增加，激活频率的逐渐降低。因此我们 具体目的是：1。在阵发性和慢性AF的患者中，以高分辨率进行量化 内膜内膜的主要频率（DF）和规律性指数（RL）！电信号作为独立的 速率和破碎的度量。 2。在阵发性和慢性AF的患者中也 通过研究腺苷输注对DF的影响来区分重入和焦点AF驱动因素 和RL分布。 3。在阵发性AF患者中，以确定快速的“崩溃频率” 在存在和不存在腺苷的情况下起搏会导致波前碎片化，反映 从1：1 LA：RA激活到支架传导的突然变化。 4。在计算机模拟中，研究 使用三种不同的计算机模型，在PV/LA交界处的AF的启动和维护机制 随着解剖复杂性的增加。成功实现我们的特定目标应该有助于我们进步 理解这种复杂心律不齐的机制和表现，可能有助于直接 提高药理学和消融疗法在患者中的功效。