CARDIAC NEUROMODULATION IN HUMANS: MECHANISMS & THERAPIES

心血管疾病是美国发病率和死亡率的主要原因， 整个世界。自主神经系统(ANS)在糖尿病的发病机制中起着核心作用。 几种心血管疾病，如房颤、高血压、心肌梗死 (MI)、室性快速性心律失常/纤颤(VT/VF)和心力衰竭进展 (Hf)。心力衰竭也给美国卫生系统带来了重大的财政负担，影响了 500万人，预计到2030年将增长到800万人。交感迷走神经平衡， 在正常健康中看到的，是由于心脏病的存在而心烦意乱导致的 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。神经调节疗法的目的是恢复 交感迷走神经平衡，从而试图逆转/防止心血管疾病的进展 疾病。神经调节疗法，如星状神经节切除术/心脏交感神经 去神经治疗(CSD)现在正在临床上使用，其他神经轴方法显示 有很多希望，包括迷走神经刺激(VNS)。然而，临床试验已经 结果喜忧参半，阻碍了治疗的广泛应用。这突出了主要的 关于它们的作用机制和决定的知识差距 临床环境下的最佳生物电参数和生理读数。作为一种 例如，迷走神经刺激(TVNS)，已经显示出在减少 炎症和防止进行性心肌病理性重塑。然而，几乎没有什么是 了解如何给药以最大限度地发挥TVNS在预防或 逆转已患心脏病患者的自主神经功能障碍 例如MI。在一系列的翻译/机械学研究中，神经调节将应用于 对于健康受试者和患有心脏病(MI或VT)的人，确定最佳参数和 并确定神经调节如何影响脑电生理参数。 心。

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.