Interactive Vagal Stimulation and Atrial Fibrillation

本项目的目的是开发通过低剂量的药物治疗心房颤动（AF）的方法。 强度交互式迷走神经刺激。AF是美国最常见的心律失常， 并与神经基质的自主调节有关。自主神经 活动及其对心房纤颤的影响一直是重要兴趣的主题， 受寻找更具成本效益的房颤治疗方法的推动。证据 动物研究表明，房颤的发生通常伴随着 交感神经和迷走神经的共同激活。因此，一种潜在的抑制 AF的发作是在AF发生之前抑制交感迷走神经共激活。这项研究将 测试由交感神经放电触发的低水平迷走神经刺激可以 改变AF的神经基质，改变AF的易感性。这种概念性AF治疗将 在急性和慢性AF犬模型中进行测试。 被动迷走神经刺激，将建立一种新的植入式交互式迷走神经刺激器（I-VS）。的 交互式刺激器仅在交感神经活动高时触发。本研究的目的是 1)评价I-VS在开胸急性准备中的有效性。I-VS将被设计成 在诱发房颤的急性开胸准备中进行测试。交互式起搏算法将 检测用于触发迷走神经刺激的交感神经活动。的算法 交互式起搏将首先用数据采集软件实现，然后用硬件实现 基于由以下确定的系统参数设计植入式神经刺激器 软件操作。将确定刺激脉冲的频率和强度 基于其在诱发AF期间改变自主放电的能力。2）评估 I-VS在非卧床慢性制剂中的疗效。交互式神经刺激器 封装并植入动物体内用于以后的迷走神经刺激。房颤将由以下因素诱发： 心房的慢性间歇性快速起搏。AF诱导将与 没有交互式迷走神经刺激。在持续性AF期间将再次应用I-VS， 描述迷走神经刺激引起的自主神经放电的变化。的能力 连续记录并实时解释心脏神经活动不仅可以 心脏病进展期间自主活动的特征，而且 为自主系统的电干预提供了一个令人兴奋的机会。结果 这项研究将促使新的研究进一步开发自主神经刺激的潜力， 作为一种新的房颤治疗模式。

The objective of this project is to develop method for treating atrial fibrillation (AF) by low- intensity interactive vagal stimulation. AF is the most common arrhythmia in the United States, and has been associated with autonomic modulation of neural substrate. The autonomic nerve activity and its effect on atrial fibrillation has been a subject of significant interests, largely driven by the search for more cost-effective treatments for atrial fibrillation. Evidence from animal studies shows that the initiation of atrial fibrillation is usually accompanied by coactivation of sympathetic and vagal nerves. Therefore, one potential approach to suppress the onset of AF is to inhibit the sympathovagal coactivation before AF occurs. This research will test the hypothesis that low-level vagal stimulation triggered by sympathetic discharges can modify neural substrate of AF and alter AF susceptibility. Such a conceptual AF treatment will be tested in acute and chronic canine models of AF. Unlike the conventional approach of passive vagal stimulation, a new implantable interactive vagal stimulator (I-VS) will be built. The interactive stimulator fires only when the sympathetic activity is high. The aims in this study are 1) Evaluate the efficacy of I-VS in open-chest acute preparations. The I-VS will be designed and tested in acute open-chest preparations with induced AF. The interactive pacing algorithm will detect sympathetic nerve activities for triggering the vagal stimulation. The algorithm of interactive pacing will be first implemented with data acquisition software, followed by hardware design of an implantable neural stimulator based on the system parameters determined from the software operation. The frequency and intensity of the stimulation pulses will be determined based on their ability to alter autonomic discharges during the induced AF. 2) Evaluate the efficacy of I-VS in ambulatory chronic preparations. The interactive neural stimulator will be encapsulated and implanted in animals for later vagal stimulation. The AF will be induced by chronic, intermittent fast pacing of the atrium. The AF inducibility will be compared with and without the interactive vagal stimulation. The I-VS will be again applied during sustained AF to characterize the change of autonomic discharges due to vagal stimulation. The capability to record continuously and interpret in real-time the cardiac nerve activities not only allows characterization of autonomic activities during the progression of heart disease, but also presents as an exciting opportunity for electrical intervention of the autonomic system. Results from this study will prompt new studies to further exploit the potential of autonomic stimulation as a new AF treatment paradigm.