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.

人类心房颤动（AF）的机制尚不清楚。既往离体动物心脏