Deglutitive and airway protective functions of proximal/ striated muscle esophagus in health and disease

近端/横纹肌食管在健康和疾病中的吞咽和气道保护功能

• 批准号: 10418013
• 负责人: REZA NONE SHAKER
• 金额: $ 45.14万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-20 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10418013
• 关键词: Age; Anatomy; Aspiration Pneumonia; Biomechanics; Body Weight decreased; Bolus Infusion; Cessation of life; Clinic; Cricoid cartilage structure; Data; Deglutition; Deglutition Disorders; Development; Devices; Disease; Elderly; Esophagus; Event; Exhibits; Family Felidae; Fluoroscopy; Functional disorder; Health; Human; Independent Living; Injections; Investigation; Laboratories; Larynx; Lead; Liquid substance; Malnutrition; Manometry; Methods; Modeling; Motor; Neurodegenerative Disorders; Patients; Penetration; Peristalsis; Persons; Phase; Physiological; Positioning Attribute; Property; Quality of life; Reflex control; Reflux; Reporting; Rest; Risk; Secondary to; Striated Muscles; Testing; accurate diagnosis; age related; body position; clinically relevant; cost estimate; digital; electric impedance; multidisciplinary; novel; post stroke; pressure; prevent; relating to nervous system; response; stroke patient; volunteer

Esophageal motor function is a key player in both swallowing and airway protection, but these functions have not been systematically investigated in proximal/striated esophagus (St.Eso) despite its proximity to the airway and the risk of aspiration due to its dysfunction. Our preliminary studies reveal important novel findings with significant clinical relevance about St.Eso functions that led to the development of hypotheses to be tested in this proposal. There are two specific aims in this proposal. In Specific Aim I we will characterize the St.Eso deglutitive motor function and its modulation by pharyngeal swallow biomechanics. We will test the following Hypotheses 1) St.Eso. motor function constitutes four distinct components in relation to its deglutitive excursion associated with laryngeal elevation: a. Increased wall tension commensurate to the magnitude of its anterosuperior excursion, b. Non-peristaltic bolus receiving function during UES opening, c. Peristaltic / bolus transport function as it descends and d. Continued peristalsis in its resting position. 2. Components of St.Eso motor function are correlated with and can be modulated by pharyngeal biomechanics and related pressures. SA 1A: In healthy and patient volunteers, we will determine and characterize the: i. non-peristaltic and peristaltic components of the St.Eso motor functions and their relationship with pharyngeal phase biomechanics, ii. effect of experimentally enhancing and reducing pharyngeal biomechanics on St.Eso. motor functions, iii. St.Eso peristalsis parameters and its modulation by bolus type, volume, body positions and age using state-of- the-art concurrent HRM/impedance manometry/ digital video fluoroscopy and our novel experimental devices. SA 1B: In our feline model we will: i. characterize the relationship between superior laryngeal excursion and components of St.Eso motor functions during swallowing, i.e. pre-peristaltic St.Eso wall tension, bolus injection distance, and peristaltic magnitude, ii. determine the mechanisms of these functions, the possible mechanisms include ENS and CNS neural reflex control and biomechanical properties of the St.Eso. In specific Aim 2 we will Characterize the St.Eso. airway protective function and its relationship with that of the UES and esophageal secondary peristalsis. We will test the following hypotheses: 1) St.Eso. responds to reflux events independent of secondary peristalsis by a lumen occluding contraction fortifying the UES pressure response. 2) This response is i. age dependent and is related to the type, quantity, and velocity of the refluxate and ii. absent or discordant with the UES response in disease states. SA 2A: In healthy and patient volunteers we will characterize the St.Eso. responses to i. physiologic reflux, and ii. simulated reflux events (non-acidic and acidic fluids with various volumes and rates). SA 2B: We will determine in both groups the: i. concordance of St.Eso and UES responses to simulated and physiologic reflux events, ii. functional relationship of St.Eso. response to that of the secondary peristalsis.

食道运动功能在吞咽和呼吸道保护中都起着关键作用，但这些功能 尚未对近端/横纹食道(St.Eso)进行系统研究，尽管它靠近 呼吸道和因其功能障碍而导致的吸入风险。我们的初步研究揭示了重要的新发现 与St.Eso功能有显著的临床相关性，导致了要测试的假说的发展 在这份提案中。这项提议有两个具体目标。 在特定的目标I中，我们将描述St.Eso吞咽运动功能及其咽部的调节 吞下生物力学。我们将检验以下假设：1)圣埃索。运动功能构成四个不同的 与喉部抬高相关的吞咽运动相关成分：a.喉壁张力增加 与其前上偏移的大小相称，b.非蠕动推注接收功能 Us打开，c.蠕动/推进器在下降时起作用，d.在静止时继续蠕动 位置。2.圣埃索运动功能的组成部分与咽部相关，并可被咽部调节 生物力学和相关压力。 SA：在健康和患者志愿者中，我们将确定和描述：I.非蠕动和 圣埃索运动功能的蠕动成分及其与咽相生物力学的关系， 二、实验性增强和降低咽部生物力学对St.Eso的影响。运动功能，III。 St.Eso蠕动参数及其随推注类型、体积、体位和年龄的调节 最先进的HRM/阻抗测压/数字视频透视和我们的新型实验设备。 SA 1B：在我们的猫模型中，我们将：I.描述喉上移位之间的关系 和吞咽时St.Eso运动功能的组成部分，即蠕动前St.Eso壁张力，团注 喷射距离和蠕动幅度，ii。确定这些功能的机制，可能的 其机制包括ENS和CNS的神经反射控制以及St.Eso的生物力学特性等。 在具体目标2中，我们将描述圣埃索的特征。呼吸道保护功能及其与慢性阻塞性肺疾病的关系 UES和食道二次蠕动。我们将检验以下假设：1)圣埃索。响应于 通过闭塞收缩增强UES压力的管腔独立于二次蠕动的回流事件 回应。2)这种反应是年龄相关的，并与返流的类型、数量和速度有关。 和II.没有或与疾病状态下的UES反应不一致。 SA 2A：在健康和患者志愿者中，我们将描述St.Eso的特征。对I.生理反应 回流，以及II。模拟回流事件(不同体积和速率的非酸性和酸性流体)。 SA 2B：我们将在两组中确定：I.St.Eso和UES对模拟的响应的一致性 生理性反流事件，II。圣埃索的功能关系。对二次蠕动的反应。