ATRIAL FIBRILLATION AND FLUTTER IN A MODEL

模型中的心房颤动和扑动

• 批准号: 2218823
• 负责人: ALBERT L WALDO
• 金额: $ 29.92万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2218823
• 关键词: antiarrhythmic agent; atrial fibrillation; disease /disorder model; disease /disorder prevention /control; dogs; electrocardiography; electrophysiology; epicardial mapping; heart disorder diagnosis; heart pharmacology; nonhuman therapy evaluation

There are two long term objectives of this research plan; 1) to use electrophysiological and pharmacological techniques to improve our understanding of the mechanisms responsible for atrial fibrillation and atrial flutter, and 2) to develop an improved basis for their treatment. The specific aims of the research plan are 1) to identify the mechanism of atrial fibrillation in a newly described canine sterile pericarditis model with respect to its onset (induction), maintenance, termination (spontaneous or drug induced) and prevention (by drugs or creation of selected lesions); 2) to characterize the interrelationship between atrial flutter and atrial fibrillation in the sterile pericarditis model; and 3) to build on our previous studies of the sterile pericarditis atrial flutter model such that we better understand the components of its functionally determined reentrant circuit, especially the excitable gap, the areas of slow conduction, and the site of block of the circulating wave front during selected interventions. The central hypothesis is that atrial fibrillation in the sterile pericarditis model is generated by a single, unstable, right atrial free wall reentrant circuit (rotor) of short cycle length which drives both atria, migrates about the right atrial free wall, and cyclically disappears and reforms, whereas atrial flutter is generated by a single, stable right atrial free wall rotor. All other hypotheses relate directly or indirectly to this theme and include a series of hypotheses related to each of the specific aims. Methods to be used in these atrial arrhythmia models include the use of aseptic surgery to create the sterile pericarditis canine model; use of standard surgical techniques to expose the heart for mapping studies in the chronic sterile pericarditis model and in normal hearts; use of simultaneous multisite (multiplexing) recording techniques during the various electrophysiologic studies; the use of cardiac pacing techniques; the use of standard pharmacological techniques during the administration of selected agents; and the use of standard microelectrode techniques. The health relatedness of the project is clear, in that both atrial fibrillation and atrial flutter are well known, clinically troublesome, and poorly understood rhythms which adversely affect large numbers of patients. The proposed studies should provide important new information to assist in improved understanding and treatment of patients suffering from these rhythm disorders.

该研究计划有两个长期目标。 1）使用 电生理和药理技术改善我们的 了解负责房颤的机制和 心房颤动，以及2）为治疗的改进基础。 研究计划的具体目的是1）确定的机制 新描述的犬无菌心包炎模型中的心房颤动 关于其发作（归纳），维护，终止 （自发或药物引起的）和预防（通过药物或创造 选定的病变）； 2）表征房屋之间的相互关系 无菌心包炎模型中的颤音和心房颤动； 3） 以我们先前对无菌心包炎心房颤动的研究为基础 模型使我们更好地了解其功能的组成部分 确定的恢复电路，尤其是令人兴奋的差距 缓慢的传导，以及循环波侧块的位置 选定的干预措施。 中心假设是房颤 在无菌心包炎中，模型由一个单一的，不稳定的，正确的 短周期长度的房屋无壁回收电路（转子） 驱动双方，朝右心房围墙迁移，然后 周期性消失和改革，而心房的颤动是由 一个稳定的右心房壁旋转。 所有其他假设均相关 直接或间接地与此主题一起，并包括一系列假设 与每个特定目标有关。 这些房屋中使用的方法 心律失常模型包括使用无菌手术来创建无菌 心包炎犬模型；使用标准手术技术暴露 在慢性无菌心包炎模型和 在正常的心中；同时使用多站点（多路复用）记录 在各种电生理研究期间的技术；使用 心脏起搏技术；标准药理技术的使用 在选定代理的管理期间；和标准的使用 微电极技术。 该项目的健康相关性很明确， 因为房颤和心房颤动都是众所周知的 临床上麻烦，理解的节奏不利 影响大量患者。 拟议的研究应提供 重要的新信息以帮助改善理解和治疗 患有这些节奏疾病的患者。