ORGANIZATION OF EXCITATION IN HUMAN ATRIAL FIBRILATION

人心房颤动的兴奋组织

• 批准号: 7314388
• 负责人: OMER BERENFELD
• 金额: $ 27.83万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7314388
• 关键词: adenosine; atrial fibrillation; cardiovascular pharmacology; cell cell interaction; chronic disease /disorder; computer simulation; heart conduction system; heart electrical activity; human subject; pathologic process; patient oriented research

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.

人们对人类心房颤动（AF）的机制知之甚少。以前分离的动物心脏 实验表明，某些急性房颤病例可以通过不间断的周期性治疗来维持。 位于 LA 后壁、PV/LA 附近的少量离散折返位点（转子）的活动 交界处。在这些实验中，最快的转子充当主频率源（驱动器）， 维持了整体活跃度。这导致了整个两个局部激励频率的层次结构 心房。最近，临床研究证实了等级组织的存在 阵发性和慢性心房颤动患者心房不同区域的激活。然而， 这种等级制度背后的机制；人类 AF 的频率分布尚未确定 探索过。我们的一般假设是局部激活频率和规律性程度，而 心房的不同部位不同，分布非随机，在不同部位有不同的分布模式 阵发性房颤患者与慢性房颤患者。我们进一步推测这种模式是纤维颤动的结果 位于最高频率和组织位置的 AF 驱动器发出的波的传导 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（Rl）！电信号作为单独的 分别衡量速率和碎片。 2. 对于阵发性和慢性 AF 患者， 通过研究腺苷输注对 DF 的影响来区分折返性和局灶性 AF 驱动因素 和 Rl 分布。 3. 对于阵发性房颤患者，确定快速治疗的“击穿频率” 在存在和不存在腺苷的情况下起搏会导致波前碎片，这反映在 从 1:1 LA:RA 激活突然转变为颤动传导。 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 交界处启动和维持 AF 的机制 随着解剖结构复杂性的增加。成功实现我们的具体目标应该有助于我们前进 了解这种复杂心律失常的机制和表现可能有助于直接 提高患者药物和消融治疗的疗效。