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检验以下假设：同时交感迷走神经放电是阵发性房颤（PAF）的直接触发因素，切断自主神经与心脏之间的连接可以降低PAF的发生率。植物神经系统在PAF的发生发展中起重要作用。然而，没有研究记录了自主神经放电和PAF的机制之间的直接关系，在走动的动物。自主神经放电触发房颤的机制也知之甚少。本研究的主要目的是：（1）建立短期快速心房起搏诱发自发性阵发性房颤犬模型，同步记录心电图（ECG）、血压、左右星状神经节神经活动和心脏迷走神经活动。这些数据将用于检验以下假设：同时交感迷走神经激活是可走动犬中PAF最常见的直接触发因素。(2)我们将对肺静脉进行高密度标测，以检验以下假设：在该PAF犬模型中，刺激星状神经节和迷走神经可诱导这些静脉中的重复快速活动。结果将用于检验交感迷走神经刺激可诱导以自主神经末梢密度增加为特征的重塑肺静脉局灶性放电的假设。(3)我们将在与目标1所述相同的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，我们将对ECG、血压和自主神经活动进行长期同步记录。本研究结果将用于验证选择性心脏交感神经和迷走神经去支配可以显著降低PAF发生率的假设。(4)我们将在有或没有去甲肾上腺素和乙酰胆碱输注的情况下对犬肺静脉进行同步膜电位和细胞内钙标测。这些结果将用于检验体外犬PV中同时去甲肾上腺素和乙酰胆碱刺激通过Ca瞬时触发机制促进触发活动的假设。

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.