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.

项目总结/摘要 使用自主神经调节作为治疗的主要障碍之一是无法 进入支配腹部和胸部终末器官的自主神经的外周分支 蛀牙通过在周围自主神经上放置电极，将有可能记录和调节这些神经元。 神经和复制或抑制各种自主生理功能。与迷走神经干相反 刺激，周围迷走神经刺激的效果将针对特定的器官，并且可以 对特定的生理效应有特异性。此外，我们假设，这些影响可以或多或少 通过在一定范围内改变神经信号的频率、强度和/或持续时间， 产生全身副作用。 食道内窥镜检查使用Z轨道隧道通过食道和/或胃进入胃。 神经和器官的胸腔和腹腔的微创方式。最低限度地使用- 侵入性技术，容易获得安全可靠的胸腔和腹腔通路， 病人可于手术后当日回家。 本研究的主要目的是：1）建立猪的模型、方法、技术、工具 以及执行透壁内窥镜检查以识别、定位和放置电极的装置 迷走神经的外周分支，以记录和刺激靠近终末器官的神经， 2)在POEM手术中将这项技术用于人类。神经靶点和终末器官， 可以通过食道到达的是肺、心脏、食道、胸腔的小血管和大血管 和胃。可以通过胃到达的器官有胃，肝脏，胰腺，肾脏， 小肠、腹部大血管和小血管、脾脏和结肠。 这些技术有可能治疗许多疾病，这些疾病对刺激大脑皮层有反应。 自主神经系统我们对治疗慢性病的未来前景特别乐观。 高血压、糖尿病、GERD、胃轻瘫、终末期CHF、终末期肺病， 肺动脉高压和肥胖，仅举几个明显的例子， 神经修饰可能对寿命和生活质量产生重大影响。我们很高兴能做出贡献 下一代神经调节设备的开发和PNS的映射作为神经调节的一部分， 程序。