Using the GI Tract as a Window to the Autonomic Nervous System in the Thorax and in the Abdomen

使用胃肠道作为胸部和腹部自主神经系统的窗口

• 批准号: 10008166
• 负责人: LARRY S MILLER
• 金额: $ 116.27万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10008166
• 关键词: Abdomen; Abdominal Cavity; Acute; Autonomic nervous system; Autopsy; Blood Vessels; Cadaver; Caliber; Chest; Chronic; Clinical; Colon; Custom; Detection; Development; Devices; Diabetes Mellitus; Diagnostic; Disease; Electrodes; Endoscopes; Endoscopy; Esophagus; Excision; Family suidae; Frequencies; Future; Gastroesophageal reflux disease; Gastrointestinal tract structure; Gastroparesis; Goals; Heart; Home environment; Human; Hypertension; Image; Implant; Implanted Electrodes; Kidney; Knowledge; Laparoscopy; Liver; Location; Longevity; Lung; Lung diseases; Maps; Methodology; Methods; Modeling; Modification; Names; Nerve; Obesity; Operative Surgical Procedures; Optics; Oral; Organ; Pancreas; Patients; Peripheral; Peripheral Nerves; Physiological; Procedures; Pulmonary Hypertension; Quality of life; Resolution; Signal Transduction; Small Intestines; Spleen; Stomach; Structure; Techniques; Technology; Testing; Thoracic cavity structure; Thoracoscopy; Translating; Ultrasonography; Vagus nerve structure; Visual; autonomic nerve; design; design and construction; digital; experimental study; first-in-human; flexibility; implantation; interest; microendoscope; minimally invasive; neuroregulation; neurotransmission; next generation; programs; side effect; tool; tool development

Project Summary/Abstract One of the main stumbling blocks to using autonomic nerve modulation, as a therapy, is the inability to access peripheral branches of autonomic nerves innervating end organs in the abdominal and thoracic cavities. By placing electrodes on peripheral autonomic nerves, it will be possible to record and modulate these nerves and reproduce or inhibit various autonomic physiologic functions. In contrast to truncal vagal nerve stimulation, the effects of peripheral vagal nerve stimulation will be targeted at specific organs, and can be specific for particular physiologic effects. In addition, we hypothesize that the effects can be made more or less intense by varying the frequency, strength and/or duration of the nerve signal within a range that will not engender systemic side effects. Transmural endoscopy uses Z track tunneling through the esophagus and/or stomach to access the nerves and organs of the thoracic and abdominal cavity in a minimally-invasive manner. Using this minimally- invasive technique, safe and reliable access to the thoracic and abdominal cavity is easily obtained, and patients can go home on the same day after the procedure. The main objectives of the current study are to 1) develop a swine model, methods, technology, tools and devices to perform transmural endoscopy in order to identify, localize and place electrodes on the peripheral branches of the Vagus nerve, in order to record and stimulate the nerve near to the end organ and 2) to transition this technology for use in humans during POEM procedures. Nerve targets and end organs that can be reached through the esophagus are the lungs, heart, esophagus, small and great vessels of the thorax and stomach. Organs that can be reached through the stomach are the stomach, liver, pancreas, kidneys, small intestine, large and small vessels of the abdomen, spleen and colon. These techniques have the potential to treat many diseases that respond to stimulation of the autonomic nervous system. We are particularly optimistic about the future prospects of treating chronic hypertension, diabetes, GERD, gastroparesis, end stage CHF, end stage pulmonary disease such as pulmonary hypertension, and obesity to name a few of the obvious examples where peripheral autonomic nerve modification could have a significant impact on longevity and quality of life. We are excited to contribute to the development of next generation of neuromodulation devices and mapping of the PNS as a part of the SPARC program.

项目摘要/摘要 使用自主神经调节的主要绊脚石之一是一种疗法，是无法 自主神经支配腹部和胸腔内器官支配的自主神经的外围分支 腔。通过将电极放在外围自主神经上，可以记录和调节这些 神经并繁殖或抑制各种自主性生理功能。与截短的迷走神经相反 刺激，周围迷走神经刺激的影响将针对特定的器官，可以是 特定于特定的生理效应。此外，我们假设可以或多或少地产生效果 通过改变神经信号的频率，强度和/或持续时间来强烈 产生系统性副作用。 透壁内窥镜检查使用Z轨道隧道通过食道和/或胃进行 胸腔和腹腔的神经和器官以微不足道的方式。使用此最小 很容易获得侵入性技术，安全可靠的胸腔和腹腔的通道，以及 手术后的同一天，患者可以回家。 当前研究的主要目标是1）开发猪模型，方法，技术，工具 和执行透壁内窥镜检查以识别，定位和将电极放在上面的设备 迷走神经的外围分支，以记录和刺激靠近末端器官的神经和 2）在诗过程中过渡这项技术以用于人类。神经靶和结束器官 可以通过食道到达的是肺，心脏，食道 和胃。可以通过胃到达的器官是胃，肝脏，胰腺，肾脏， 腹部，脾和结肠的小肠，大和小血管。 这些技术有可能治疗许多应对刺激的疾病 自主神经系统。我们对治疗慢性的未来前景特别乐观 高血压，糖尿病，GERD，胃轻瘫，终阶段CHF，末期肺疾病，例如 肺动脉高压和肥胖，列举一些明显的例子，其中外周自主神经 神经修饰可能会对寿命和生活质量产生重大影响。我们很高兴能做出贡献 开发下一代神经调节设备和PNS的映射作为一部分 SPARC程序。