Autonomic Nerve Activity and Paroxysmal Atrial Fibrillation

描述（由申请人提供）：本研究项目的广泛和长期目标是验证同时交感迷走神经放电是阵发性心房颤动（PAF）的直接触发因素的假设，以及切断自主神经和心脏之间的联系可以减少PAF的发生。自主神经系统被认为在介导PAF中起重要作用。然而，没有研究证明自主神经放电与动态动物PAF机制之间的直接关系。自主神经放电触发心房颤动的机制也知之甚少。本课题的研究目的如下：(1)对短期快速心房起搏诱发的犬自发性PAF模型进行长期同时记录心电图、血压、左右星状神经节神经活动和心脏迷走神经活动。这些数据将用于验证同时交感迷走神经激活是活动犬PAF最常见的直接触发因素的假设。(2)我们将对肺静脉进行高密度测绘，以验证在该犬PAF模型中，通过刺激星状神经节和迷走神经可以诱导这些静脉重复快速活动的假设。该结果将用于验证假设，即交感迷走神经刺激可以诱导以自主神经末梢密度增加为特征的重塑肺静脉的局灶性放电。(3)我们将在与Aim 1中描述的PAF动物模型相同的动物模型中进行左星状神经节和心脏迷走神经的冷冻消融。然后，我们将对心电图、血压和自主神经活动进行长期同步记录。该结果将用于验证选择性心脏交感神经和迷走神经去神经可以显著降低PAF发生率的假设。(4)我们将在输注去甲肾上腺素和乙酰胆碱或不输注去甲肾上腺素和乙酰胆碱的情况下同时对犬肺静脉进行膜电位和细胞内钙绘图。该研究结果将用于验证犬科动物体外去甲肾上腺素和乙酰胆碱同时刺激PV通过Ca瞬时触发机制促进触发活性的假设。

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.