CARDIAC NEUROMODULATION IN HUMANS: MECHANISMS & THERAPIES

人类心脏神经调节：机制

• 批准号: 10190645
• 负责人: KALYANAM SHIVKUMAR
• 金额: $ 73.03万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-23 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10190645
• 关键词: Affect; Atrial Fibrillation; Autonomic Dysfunction; Autonomic nervous system; Cardiac; Cardiovascular Diseases; Clinical; Clinical Trials; Dose; Electrophysiology (science); Equilibrium; Financial Hardship; Ganglionectomy; Health; Health system; Heart; Heart Diseases; Heart failure; Human; Hypertension; Inflammation; Knowledge; Morbidity - disease rate; Myocardial; Myocardial Infarction; Output; Pathogenesis; Pathologic; Patients; Physiological; Play; Role; Series; Sympathectomy; Tachyarrhythmias; Ventricular; bioelectricity; mortality; neuroregulation; prevent; vagus nerve stimulation

Cardiovascular disease is the leading cause of morbidity and mortality in the US and the world. The autonomic nervous system (ANS) plays a central role in the pathogenesis of several cardiovascular diseases such as atrial fibrillation, hypertension, myocardial infarction (MI), ventricular tachyarrhythmias/fibrillation (VT/VF) and in the progression of heart failure (HF). Heart failure also places a major financial burden on the US health system, affecting five million people, and it is estimated to grow to eight million by 2030. Sympathovagal balance, seen in normal health, is perturbed in the presence of cardiac disease leading to ‘net’ sympathoexcitation, which is due to an increase in sympathetic output and a concomitant decrease in parasympathetic output. Neuromodulation therapies are directed toward restoring sympathovagal balance and thereby attempt to reverse/prevent progression of cardiovascular disease. Neuromodulation therapies such as stellate ganglionectomy/cardiac sympathetic denervation (CSD) are now being clinically utilized and other neuraxial approaches show a lot of promise including vagus nerve stimulation (VNS). However, clinical trials have shown mixed results preventing broad application of therapy. This highlights the major knowledge gap that exists regarding their mechanisms of action and the determination of optimal bioelectric parameters and physiological readouts in the clinical setting. As an example, tragal vagus nerve stimulation (TVNS), has demonstrated potential benefit in reducing inflammation and preventing progressive myocardial pathological remodeling. However, little is known about how to dose the therapy to maximize the effects of TVNS in preventing or reversing autonomic dysfunction in patients who have already suffered from cardiac disease such as MI. In a series of translational/mechanistic studies, neuromodulation will be applied to healthy subjects and to those with heart disease (MI or VT) to define optimal parameters and readouts and to determine how neuromodulation impacts electrophysiological parameters of the heart.

心血管疾病是美国和美国发病率和死亡率的主要原因 世界。自主神经系统（ANS）在疾病的发病机制中起着核心作用 房颤、高血压、心肌梗塞等多种心血管疾病 (MI)、室性快速心律失常/颤动 (VT/VF) 以及心力衰竭的进展 （高频）。心力衰竭还给美国卫生系统带来重大经济负担，影响 500 万人，预计到 2030 年将增长到 800 万人。交感迷走神经平衡， 在正常健康状况下可见，在心脏病存在时会受到干扰，导致“净” 交感神经兴奋，这是由于交感神经输出的增加和伴随的 副交感神经输出减少。神经调节疗法旨在恢复 交感迷走神经平衡，从而尝试逆转/预防心血管疾病的进展 疾病。神经调节疗法，例如星状神经节切除术/心脏交感神经术 去神经术 (CSD) 现已在临床上使用，其他椎管内治疗方法也显示出 很多希望包括迷走神经刺激（VNS）。然而，临床试验已 结果好坏参半，阻碍了治疗的广泛应用。这突出了主要 关于其作用机制和确定的知识差距 临床环境中的最佳生物电参数和生理读数。作为一个 例如，耳屏迷走神经刺激（TVNS）已被证明在减少 炎症并预防进行性心肌病理性重塑。然而，很少的是 了解如何调整治疗剂量以最大限度地发挥 TVNS 在预防或治疗方面的作用 逆转已患有心脏病的患者的自主神经功能障碍 例如MI。在一系列转化/机制研究中，神经调节将被应用于 健康受试者和心脏病患者（MI 或 VT）以确定最佳参数和 读数并确定神经调节如何影响电生理参数 心。