Autonomic Nerve Activity and Paroxysmal Atrial Fibrillation

自主神经活动与阵发性心房颤动

基本信息

批准号：
7895835
负责人：
PENG-SHENG CHEN
金额：
$ 46.37万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7895835
关键词：
Abbreviations Ablation Acetylcholine Action Potentials Adrenergic Agents Animal Model Animals Atrial Fibrillation Atrioventricular Block Autonomic nervous system Blood Pressure Calcium Canis familiaris Cardiac Cardiac ablation Chest Clinical Research Congestive Heart Failure Cryosurgery Data Denervation Dissociation Electrocardiogram Funding Generations Growth Associated Protein 43 Harvest Heart Heart Atrium Human In Vitro Incidence Infusion procedures Laboratories Left Left atrial structure Ligaments Maintenance Maps Marshal Mediating Membrane Potentials Methods Modeling Myocardial Infarction Nerve Nerve Endings Nerve Growth Factors Norepinephrine Optics Parasympathetic Nervous System Pulmonary veins Recurrence Research Personnel Research Project Grants Right atrial structure Right ventricular structure Site Source Structure of stellate ganglion Superior vena cava structure Surveys Sympathetic Ganglia Tachycardia Techniques Testing Time Tissues Transferase Tyrosine 3-Monooxygenase Veins Ventricular Fibrillation Ventricular Tachycardia adrenergic autonomic nerve density design heart rate variability insight programs radiofrequency relating to nervous system voltage

项目摘要

DESCRIPTION (provided by applicant): The broad and long-term objective of this research project is to test the hypothesis that simultaneous sympathovagal discharges are the immediate triggers of paroxysmal atrial fibrillation (PAF) and that severing the connection between the autonomic nerves and the heart can reduce the incidence of PAF. Autonomic nervous system is thought to be important in mediating PAF. However, no studies have documented a direct relationship between autonomic nerve discharges and the mechanisms of PAF in ambulatory animals. The mechanisms by which autonomic nerve discharges trigger AF are also poorly understood. The research project is designed to accomplish the following specific aims: (1) We will perform long-term simultaneous recordings of electrocardiogram (ECG), blood pressure, right and left stellate ganglion nerve activity and cardiac vagal nerve activity in a canine model of spontaneous PAF induced by short-term rapid atrial pacing. The data will be used to test the hypothesis that simultaneous sympathovagal activation is the most common immediate trigger of PAF in ambulatory dogs. (2) We will perform high density mapping of pulmonary veins to test the hypothesis that repetitive rapid activities in these veins can be induced by stimulation of stellate ganglia and vagal nerves in this canine model of PAF. The results will be used to test the hypothesis that sympathovagal stimulation can induce focal discharges from the remodeled pulmonary veins characterized by an increased density of autonomic nerve endings. (3) We will perform cryoablation of the left stellate ganglion and cardiac vagal nerves in the same animal models of PAF as that described in Aim 1. We will then perform long-term simultaneous recordings of ECG, blood pressure and autonomic nerve activities. The results will be used to test the hypothesis that selective cardiac sympathetic and vagal denervation can significantly reduce the incidence of PAF. (4) We will perform simultaneous membrane potential and intracellular calcium mapping of canine pulmonary veins with or without norepinephrine and acetylcholine infusion. The results will be used to test the hypothesis simultaneous norepinephrine and acetylcholine stimulation in canine PV in vitro promotes triggered activity through Ca transient triggering mechanisms.

描述（由申请人提供）：该研究项目的广泛和长期目标是检验以下假设：同时交感神经放电是阵发性心房颤动（PAF）的直接触发器，即断断自主神经和心脏之间的联系可以减少PAF的入院率。自主神经系统被认为在介导PAF中很重要。但是，尚无研究记录自主神经排放与卧床动物中PAF机制之间的直接关系。自主神经排出触发AF的机制也很熟悉。该研究项目旨在实现以下特定目的：（1）我们将在短期自发性PAF的犬类模型中进行长期同时记录心电图（ECG），血压，左右星状神经节神经活动和心脏迷走神经活动。数据将用于检验以下假设：同时交感神经激活是卧床犬中PAF的最常见触发器。（2）我们将对肺静脉进行高密度映射，以测试以下假设：在这种PAF的犬类模型中，可以通过刺激星状神经节和迷走神经来诱导这些静脉中的重复性快速活动。结果将用于检验以下假设：交感神经刺激可以诱导重塑的肺静脉的局灶性排出，其特征在于自主神经末端的密度增加。（3）我们将在与AIM 1中所述的PAF动物模型中对左星状神经和心脏迷走神经进行冷冻化。然后，我们将对ECG，血压和自主神经活动进行长期同时记录。结果将用于检验以下假设：选择性心脏交感神经和迷走神经的神经保护可显着降低PAF的发生率。（4）我们将对有或没有去甲肾上腺素和乙酰胆碱输注的犬肺静脉的同时膜电位和细胞内钙图。结果将用于测试犬PV中同时去甲肾上腺素和乙酰胆碱刺激的假设，从而通过CA瞬时触发机制促进了触发的活性。