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.

心血管疾病是美国发病率和死亡率的主要原因， 世界。自主神经系统（ANS）在 多种心血管疾病，例如房颤，高血压，心肌梗塞 （MI），心室心律失常/纤颤（VT/VF）以及心力衰竭的进展 （HF）。心力衰竭还对美国卫生系统造成了重大财务燃烧，影响 500万人，据估计到2030年将增长到800万。 在正常健康状态下，在心脏病的存在下会受到干扰 交感神经，这是由于交感神经输出的增加和伴随的 减少副交感神经输出。神经调节疗法针对恢复 交感神经平衡，从而试图逆转/防止心血管进展 疾病。神经调节疗法，例如星状神经节切除术/心脏交感神经 神经（CSD）现在正在临床上使用，其他神经氧化方法显示 包括迷走神经刺激（VNS）的有希望。但是，临床试验有 显示出混合的结果，可防止治疗的广泛应用。这突出了专业 有关其行动机制和确定的知识差距 临床环境中的最佳生物电参数和物理读数。作为 例如，悲惨的迷走神经刺激（TVNS）在减少方面具有潜在的好处 炎症和预防进行性心肌病理重塑。但是，几乎没有 知道如何剂量的疗法以最大化电视在预防或 逆转已经患有心脏病的患者的自主神经功能障碍 例如mi。在一系列翻译/机械研究中，神经调节将应用于 健康的受试者以及患有心脏病（MI或VT）的患者，以定义最佳参数和 读数并确定神经调节如何影响的电生理参数 心。