ORGANIZATION OF EXCITATION IN HUMAN ATRIAL FIBRILATION

人类心房颤动(房颤)的发病机制尚不清楚。先前分离的动物心脏 实验证明，某些急性房颤患者可通过不间断的周期性房颤维持。 位于房室后壁、靠近PV/LA的少量离散折返点(转子)的活动 交叉口。在这些实验中，速度最快的转子充当主导频率源(驱动器)， 保持了整体的活动。这导致了本地激发频率的层次化 奥特里亚。最近，临床研究证实存在一个等级组织，其比率为 阵发性和慢性房颤患者心房不同部位的激活。然而， 在人类房颤中频率分布的这种分层的机制还没有 探索过了。我们的一般假设是局部激活频率和规律性程度，而 在中庭的不同部位分布不同，非随机分布，具有不同的分布规律 阵发性房颤患者与慢性房颤患者。我们进一步推测，这种模式是纤颤的结果。 从位于最高频率和组织位置的房颤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.在阵发性和慢性房颤患者中，以高分辨率在线量化 心内膜的优势频率(DF)和规律性指数(RL)！电信号作为独立的 分别衡量速度和碎片化程度。2.在阵发性和慢性房颤患者中， 通过研究腺苷注射对DF的影响来区分折返性房颤和局灶性房颤 和RL分布。3.在阵发性房颤患者中，确定快速跳动的“击穿频率” 在腺苷存在和不存在的情况下起搏会导致波前碎裂，表现为 从1：1LA：RA激活到纤颤传导的突变。4.在计算机模拟中，研究 用三种不同的计算机模型研究PV/LA交界处房颤的启动和维持机制 随着解剖结构的日益复杂。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 提高患者药物治疗和消融治疗的疗效。

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.