Interactive Vagal Stimulation and Atrial Fibrillation

描述(申请人提供)：本项目的目标是开发低强度交互式迷走神经刺激治疗房颤的方法。房颤是美国最常见的心律失常，与神经底物的自主神经调节有关。自主神经活动及其对房颤的影响一直是人们非常感兴趣的主题，这在很大程度上是由于寻找更具成本效益的房颤治疗方法。来自动物研究的证据表明，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，抑制房颤发生的一个可能的方法是在房颤发生前抑制交感迷走神经的共同激活。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房颤的神经底物和改变房颤易感性的假说。这种概念性的房颤治疗将在急性和慢性房颤的犬模型上进行测试。与传统的被动迷走神经刺激不同，一种新型的植入式交互式迷走神经刺激器(I-VS)将被建造。交互刺激器只有在交感神经活动较高时才会触发。本研究的目的是：1)评价I-VS在开胸急诊准备中的疗效。I-VS将在急性开胸准备中设计和测试，并诱发房颤。交互式起搏算法将检测交感神经活动以触发迷走神经刺激。交互式起搏算法将首先用数据采集软件实现，然后根据软件操作确定的系统参数设计植入式神经刺激器的硬件。刺激脉冲的频率和强度将基于它们在诱发房颤期间改变自主神经放电的能力来确定。2)评价I-VS在非卧床慢性准备中的疗效。这种交互式神经刺激器将被封装并植入动物体内，用于稍后的迷走神经刺激。房颤是由慢性、间歇性快速起搏引起的。房颤的诱发性将在有和没有交互迷走神经刺激的情况下进行比较。I-VS将在持续性房颤期间再次应用，以表征迷走神经刺激引起的自主神经放电的变化。连续记录和实时解释心脏神经活动的能力不仅允许表征心脏病进展期间的自主神经活动，而且也为自主神经系统的电干预提供了一个令人兴奋的机会。这项研究的结果将促使新的研究进一步开发自主神经刺激作为一种新的房颤治疗范例的潜力。 公共卫生相关性：房颤是美国最常见的心律失常，与自主神经调节有关。本项目中提出的自主神经刺激方法将通过改变房颤神经基质的功能来实现一种新的经济有效的房颤治疗策略。

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.