ORGANIZATION OF EXCITATION IN HUMAN ATRIAL FIBRILATION

人心房颤动的兴奋组织

• 批准号: 7496151
• 负责人: OMER BERENFELD
• 金额: $ 28.73万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-13 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7496151
• 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; Daily; Data; Dependency; Development; Distal; Electrophysiology (science); Facility Construction Funding Category; France; Frequencies; Funding Mechanisms; Hand; Heart; Heart Atrium; Human; Infusion procedures; Inpatients; Investments; Knowledge; Laboratories; Left atrial structure; Liquid substance; Localized; Location; Maintenance; Manuscripts; Maps; Measures; Modeling; Molecular; Morphology; Nature; Numbers; Optics; Pathway interactions; Patients; Pattern; Publications; Range; Rate; 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

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.

人类心房颤动（AF）的机制知之甚少。既往离体动物心脏 实验表明，某些急性AF病例可通过不间断的周期性 位于左心房后壁靠近肺静脉/左心房的少量离散折返部位（转子）的活动 交界处。在这些实验中，最快的转子充当主导频率源（驱动器）， 保持整体活动。这导致了一个层次的本地激励频率在整个两个 心房最近，临床研究证实了在发生率中存在等级组织。 阵发性和慢性房颤患者心房不同区域的激活。然而，在这方面， 这种分层的机制;人类AF频率的分布还没有被证实。 探讨了我们的一般假设是，局部激活频率和规律性程度，而 在中庭的不同部位不同，呈非随机分布， 阵发性与慢性房颤患者。我们进一步推测，这种模式是解释的结果， 位于最高频率和组织部位的AF驱动器发出的波的传导 活动，随着与驾驶员距离的增加，激活频率逐渐降低。因此我们的 具体目标是：1。在阵发性和慢性AF患者中，以高分辨率在线量化 心内膜的主频率（DF）和规律性指数（RI）！电信号作为独立的 率和碎片化的措施，分别。2.此外，在阵发性和慢性AF患者中， 通过研究腺苷输注对DF的影响，区分折返性和局灶性AF驱动因素 R1分布3.在阵发性房颤患者中，为了确定快速房颤的“击穿频率”， 在存在和不存在腺苷的情况下的起搏导致波前碎裂，其由 从1：1 LA：RA激活突然改变为代偿性传导。4.在计算机模拟中，为了研究 使用三种不同的计算机模型在PV/LA交界处启动和维持AF的机制 随着解剖学复杂性的增加。成功地实现我们的具体目标， 了解这种复杂心律失常的机制和表现，可能有助于直接 提高患者的药理学和消融治疗的功效。