Interactive Vagal Stimulation and Atrial Fibrillation

描述（由申请人提供）：该项目的目的是发展通过低强度迷走神经相互刺激治疗心房颤动（AF）的方法。房颤是美国最常见的心律失常，与神经基质的自主调节有关。自主神经活动及其对房颤的影响一直是一个重要的兴趣课题，主要是为了寻找更经济有效的房颤治疗方法。动物实验的证据表明，心房颤动的开始通常伴随着交感神经和迷走神经的共同激活。因此，抑制房颤发病的一种潜在途径是在房颤发生前抑制交感迷走神经共激活。本研究将验证交感神经放电触发的低水平迷走神经刺激可以改变AF的神经基质和改变AF易感性的假设。这种概念性房颤治疗将在急性和慢性犬房颤模型中进行测试。与传统的被动迷走神经刺激方法不同，一种新的植入式交互式迷走神经刺激器（I-VS）将被构建。互动刺激器只在交感神经活跃时才会触发。本研究的目的是：1)评价I-VS在开胸急症制剂中的疗效。I-VS将被设计和测试在急性开胸准备与诱发心房颤动。交互式起搏算法将检测交感神经活动触发迷走神经刺激。首先通过数据采集软件实现交互式起搏算法，然后根据软件运行确定的系统参数，进行植入式神经刺激器的硬件设计。刺激脉冲的频率和强度将根据其在诱发心房颤动期间改变自主神经放电的能力来确定。2)评估I-VS在动态慢性制剂中的疗效。交互式神经刺激器将被封装并植入动物体内，用于随后的迷走神经刺激。心房慢性、间歇性快速起搏可诱发房颤。将迷走神经相互刺激前后的心房感应性进行比较。在持续AF期间再次应用I-VS来表征迷走神经刺激引起的自主放电的变化。连续记录和实时解释心脏神经活动的能力不仅可以表征心脏病进展过程中的自主神经活动，而且还为自主神经系统的电干预提供了令人兴奋的机会。这项研究的结果将促使新的研究进一步挖掘自主神经刺激作为房颤治疗新范式的潜力。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Atrial fibrillation is the most common arrhythmia in the United States, and has been associated with autonomic modulation. The autonomic stimulation approach proposed in this project will enable a novel cost-effective AF treatment strategy by altering the function of AF neural substrate.