VERY LOW ENERGY CARDIOVERSION FOR ATRIAL FIBRILLATION

心房内除颤是治疗心房颤动（AF）的一种成功疗法。 目前的心房除颤器 (IAD) 使用传统的除颤技术来提供高能量电击，成功的可能性很高。所施加的3-10焦耳的冲击强度高于患者的疼痛阈值，这限制了IAD疗法的广泛应用。提出了一种利用多次极低能量（小于 0.5J）冲击（VLES）的技术，首次冲击成功的概率较低，但累积转换概率较高。 遥测系统将被植入 AF 绵羊模型中。 组合的动物模型和遥测系统将用作 VLES 心房复律的试验台。 遥测装置可在 10 米的距离内传输 4 条电图，并通过远程控制提供连续且可编程的起搏。 该系统将通过添加压力监控和 VLES 电路得到增强。 它将用于 1) 表征电重塑并跟踪快速起搏方案引起的心房压力变化，2) 测量与 5% 成功水平相对应的能量，3) 测试三种提高 VLES 成功概率的策略。 这三种策略是：1) VLES 前超速起搏 2) VLES 前基于非线性动力学的起搏，以及 3) 在 VLES 中使用 III 类抗心律失常药物。 心外膜标测将用于确定 VLES 除颤机制并表征 3 种增强策略的效果。这笔赠款中提出的工作将推进未麻醉动物远程测试的科学，将描述羊快速起搏产生的电模型和心肌病理学的发展，并将测试总共四种极低能量心房除颤策略。 这些进展将增加我们对房颤进展的了解，并使这种使人衰弱的疾病的成功疗法得到更广泛的应用。

Internal atrial defibrillation is a successful therapy for the treatment of atrial fibrillation(AF). Current internal atrial defibrillators(IAD) use conventional defibrillation technology to deliver high energy shocks with a high likelihood of success. The applied shock strength of 3-10 Joules is above a patient's pain threshold and this limits the broad application of IAD therapy. A technology is proposed that utilizes multiple very low energy (less than .5J) shocks(VLES) with a low probability of first shock success but a high cumulative probability of conversion. A telemetry system will be implanted in an ovine model of AF. The combined animal model and telemetry system will be used as a test bed for VLES atrial cardioversion. The telemetry unit transmits 4 electrograms a distance of 10 meters and delivers continuous and programmed pacing by remote control. This system will be enhanced by adding pressure monitoring and VLES circuitry. It will be used 1) to characterize electrical remodeling and to track changes in infra-atrial pressure induced by the rapid pacing protocol and 2) to measure the energy that corresponds to a 5 percent level of success, and 3) to test three strategies for increasing the VLES probability of success. The three strategies are: 1) pre-VLES overdrive pacing 2) pre-VLES non-linear dynamics based pacing, and 3) use of class III antiarrhythmic drugs with VLES. Epicardial mapping will be used to identify the mechanism of VLES defibrillation and to characterize the effects of the 3 enhancement strategies. The work proposed in this grant will advance the science of remote testing in unanesthetized animals, will characterize the development of electrical modeling and myocardial pathology produced by rapid pacing in sheep, and will test a total of four strategies for very low energy atrial defibrillation. These advances will increase our understanding of the progression of AF and allow a successful therapy for this debilitating disease to be more broadly applied.