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：
7822294
负责人：
PENG-SHENG CHEN
金额：
$ 1.79万
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：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2010-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7822294
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：同时交感迷走神经放电是阵发性心房颤动 (PAF) 的直接触发因素，并且切断自主神经和心脏之间的联系可减少PAF的发生。自主神经系统被认为在调节 PAF 中发挥着重要作用。然而，尚无研究证明动物自主神经放电与 PAF 机制之间存在直接关系。自主神经放电引发房颤的机制也知之甚少。该研究项目旨在实现以下具体目标：（1）我们将在自发性心律失常的犬模型中进行心电图（ECG）、血压、左右星状神经节神经活动和心脏迷走神经活动的长期同步记录由短期快速心房起搏引起的 PAF。这些数据将用于检验以下假设：同时交感迷走神经激活是行走犬 PAF 最常见的直接触发因素。 (2) 我们将对肺静脉进行高密度测绘，以检验这样的假设：在这种 PAF 犬模型中，刺激星状神经节和迷走神经可以诱导这些静脉的重复快速活动。结果将用于检验以下假设：交感迷走神经刺激可以诱导重塑的肺静脉的局灶性放电，其特征是自主神经末梢密度增加。 (3) 我们将在与目标 1 中描述的相同的 PAF 动物模型中对左星状神经节和心脏迷走神经进行冷冻消融。然后我们将进行心电图、血压和自主神经活动的长期同步记录。结果将用于检验选择性心脏交感神经和迷走神经去神经术可以显着降低 PAF 发生率的假设。 (4) 我们将在注射或不注射去甲肾上腺素和乙酰胆碱的情况下对犬肺静脉进行同步膜电位和细胞内钙标测。结果将用于检验体外同时刺激犬 PV 去甲肾上腺素和乙酰胆碱通过 Ca 瞬时触发机制促进触发活动的假设。