ATRIAL FIBRILLATION AND ALTERNANS OF ACTION POTENTIAL DURATION

心房颤动和动作电位持续时间的交替

• 批准号: 8169368
• 负责人: Sanjiv M Narayan
• 金额: $ 3.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8169368
• 关键词: Ablation; Action Potentials; Address; Affect; Algorithms; Anatomy; Animals; Arts; Atrial Fibrillation; Cicatrix; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Data; Data Collection; Development; Electric Countershock; Electrophysiology (science); Funding; Grant; Heart Atrium; Heart failure; Heterogeneity; Human; In Vitro; Individual; Institution; Link; Maps; Modeling; Morbidity - disease rate; Patients; Pharmaceutical Preparations; Phase; Population; Property; Pulmonary veins; Research; Research Personnel; Resources; Shapes; Sinus; Site; Source; Stroke; Structure; Symptoms; Tissues; United States; United States National Institutes of Health; Ventricular Fibrillation; X-Ray Computed Tomography; computer studies; digital; man; mortality; reconstruction; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. (A) OBJECTIVES Atrial fibrillation (AF) affects 2.2 million individuals in the United States, and is a major cause of stroke, heart failure and mortality (8). Maintaining sinus rhythm reduces symptoms and may prolong survival, yet remains difficult (1). Recent advances in ablation now make it possible to cure many patients with paroxysmal AF, whose episodes are self-limiting, by isolating triggers in the pulmonary veins (12, 14). Unfortunately, ablation is complex, and less successful in the large population with persistent AF, whose episodes require drugs or cardioversion to terminate (10). In this group, AF recurs post-ablation in > 50 %, requiring multiple ablations with attendant morbidity and mortality (5). Unfortunately, therapy is limited by a poor understanding of how, and under what conditions, AF occurs in humans. It is increasingly appreciated that structural heterogeneities or dynamic tissue properties may initiate fibrillation (33). Animal, in vitro and computational studies have shown that every-other-beat oscillations (alternans) in action potential duration (APD), may initiate ventricular fibrillation (33). Mechanistically, tissue heterogeneities such as scar, or dynamics such as steep restitution (i.e. "rate-response") of APD, conduction velocity (CV) that slows for a broad range of rates (36), may cause APD alternans. By exaggerating repolarization dispersion, particularly if discordant (33), APD alternans may be a direct mechanism for AF. Although APD alternans has yet to be linked with AF in animals or man, we have exciting preliminary data in humans showing APD alternans leading directly to reentrant AF. As a collaborative project of the NBCR this research will promote extensions to the development of Continuity and its anatomic and electrical models and patient-specific modeling algorithms that will permit greater integration with models of impulse conduction in the atria. Our central hypothesis is that Atrial Fibrillation in humans initiates from Alternans of Action Potential Duration (APD), that reflects steep restitution of atrial APD and broad restitution of regional conduction velocity, and explains AF near the pulmonary veins (PV) in paroxysmal AF but not persistent AF. This study marries sophisticated data collection in patients at AF ablation with unique state-of-the-art patient-specific computational modeling to address 3 Specific Aims. 1. To determine whether alternans of atrial action potential duration (APD), resulting from steep APD restitution or broad conduction velocity (CV) restitution, precedes the onset of Atrial Fibrillation. We will record multi-site monophasic action potentials (MAP) and CV from 64-128 bi-atrial basket poles at electrophysiologic study, with and without pharmacologic modulation, in atrial reconstructions guided by computed tomography in paroxysmal and persistent AF patients. 2. To determine whether the first beats of AF follow conduction block and reentry. We will use patient-specific structure-function data, from basket maps referenced to digital atrial anatomy, isochronal analysis and phase mapping. We will also determine if these sites lie near PVs in patients with paroxysmal AF but not persistent AF. 3. To determine whether AF is caused by atrial discordant APD alternans, by developing patient-specific computational models derived from clinically observed electrophysiology. We will develop finite-volume models that incorporate observed CV and APD restitution, atrial shape and structural heterogeneities for each patient, to compare modeled to actual AF in each patient.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 （a）目标 心房颤动（AF）在美国影响220万个人，是中风，心力衰竭和死亡率的主要原因（8）。保持窦性节奏可减少症状并可能延长生存率，但仍然很困难（1）。现在，消融的最新进展使得通过隔离肺静脉中的触发因素来治愈许多阵发性AF的患者，其发作是自限制的（12，14）。不幸的是，消融很复杂，在持续的AF的​​大人群中，其发作需要药物或心脏抗拒才能终止（10）。在这一组中，AF在> 50％> 50％的情况下复发，需要多次消融具有随之而来的发病率和死亡率（5）。不幸的是，治疗受到对人类如何以及在什么条件下如何发生AF的不良理解的限制。 越来越多地认为，结构异质性或动态组织特性可能会引发纤颤（33）。动物，体外和计算研究表明，动作电位持续时间（APD）中的每一个振动振荡（替代）可能启动心室纤颤（33）。从机械上讲，组织异质性（例如疤痕）或APD的陡峭恢复（即“速率响应”），传导速度（CV）的动力学，这些速度（CV）可能会导致广泛的速率（36），可能会导致APD替代品。通过夸大复极化分散体，特别是如果不一致（33），APD替代品可能是AF的直接机制。尽管APD Alternans尚未与动物或人的AF联系在一起，但我们在人类中仍有令人兴奋的初步数据，显示了APD替代人直接导致AF进入AF。作为NBCR的协作项目，这项研究将促进连续性及其解剖和电气模型以及特定于患者的建模算法的扩展，这些算法将允许与心房中冲动传导模型更大的整合。 我们的核心假设是，人类的房颤是由动作势持续时间（APD）的启动，反映了房屋APD的急剧恢复和区域传导速度的广泛恢复，并解释了在肺脉（PV）附近的paroxymal af，但不是在paroxymal af中但不持续的。这项研究将AF消融中患者的复杂数据收集与独特的特定于患者的计算建模相结合，以解决3个特定目标。 1。确定急性APD恢复原状或较大的传导速度（CV）恢复的替代势势持续时间（APD）是否在心房颤动的开始之前。 我们将在电生理学研究中记录从64-128个双重篮球杆的多站点单相作用电位（MAP）和CV，在有或没有药理调制的情况下，在由计算机断层扫描中的心房重建中，有或没有药理学调节。 2。确定AF的第一个节拍是否遵循传导块和再入。 我们将使用特定于患者的结构功能数据，这些数据来自引用数字心房解剖学，等体分析和相位映射的篮子图。 我们还将确定这些位点是否位于阵发性AF患者但不持续的AF患者的PV附近。 3。通过开发从临床观察到的电生理学得出的患者特异性计算模型来确定房颤是否是由心房不一致的APD替代品引起的。 我们将开发有限体积模型，这些模型包括观察到的CV和APD恢复原状，对每个患者的心房形状和结构异质性，以比较每个患者的实际AF模型。