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

基本信息

批准号：
10611445
负责人：
REZA NONE SHAKER
金额：
$ 46.9万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
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/10611445
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 Pharyngeal structure Phase Physiological Positioning Attribute Property Quality of life Reflex control Reflux Reporting Rest Risk Secondary to Striated Muscles Testing accurate diagnosis age related aspirate body position clinically relevant cost estimate digital electric impedance fortification multidisciplinary neural novel post stroke pressure prevent response stroke patient volunteer

项目摘要

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.

食管运动功能在吞咽和气道保护中发挥着关键作用，但这些功能尽管近端/横纹食管 (St.Eso) 接近食管，但尚未对其进行系统研究气道及其功能障碍导致误吸的风险。我们的初步研究揭示了重要的新发现与 St.Eso 功能具有重要的临床相关性，从而导致了待测试假设的发展在此提案中。该提案有两个具体目标。在特定目标 I 中，我们将描述 St.Eso 吞咽运动功能及其通过咽部的调节吞咽生物力学。我们将测试以下假设 1) St.Eso。运动功能由四种不同的与喉部抬高相关的吞咽行程相关的成分：a．壁张力增加与其前上方偏移的幅度相称，b．期间非蠕动推注接收功能 UES 开放，c。蠕动/推注输送功能在下降时发挥作用 d．静止状态下持续蠕动位置。 2. St.Eso 运动功能的组成部分与咽部相关并可以通过咽部调节生物力学和相关压力。 SA 1A：在健康和患者志愿者中，我们将确定并表征：非蠕动和 St.Eso 运动功能的蠕动成分及其与咽期生物力学的关系，二.实验性增强和减少咽部生物力学对 St.Eso 的影响。运动功能，三。 St.Eso 蠕动参数及其通过推注类型、体积、身体位置和年龄的调节（使用状态）最先进的并发HRM/阻抗测压/数字视频透视和我们新颖的实验设备。 SA 1B：在我们的猫科动物模型中，我们将：描述喉部上移之间的关系以及吞咽期间 St.Eso 运动功能的组成部分，即蠕动前 St.Eso 壁张力、推注注射距离和蠕动幅度，ii．确定这些功能的机制，可能的机制包括 ENS 和 CNS 神经反射控制以及 St.Eso 的生物力学特性。在具体目标 2 中，我们将描述 St.Eso 的特征。气道保护功能及其与呼吸道保护功能的关系 UES和食管二次蠕动。我们将测试以下假设：1）St.Eso。回应通过管腔闭塞收缩增强 UES 压力，实现与二次蠕动无关的反流事件回复。 2）这个响应是i。取决于年龄，并与回流液的类型、数量和速度有关 ii.疾病状态下的 UES 反应不存在或不一致。 SA 2A：在健康和患者志愿者中，我们将描述 St.Eso 的特征。对 i 的回应生理回流，以及 ii.模拟回流事件（具有不同体积和速率的非酸性和酸性液体）。 SA 2B：我们将在两组中确定： i． St.Eso 和 UES 对模拟响应的一致性和生理反流事件，ii。 St.Eso 的函数关系。对次级蠕动的反应。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biomechanical effects of esophageal elongation on the circumferential tension of the cervical esophagus in vivo.

食管伸长对体内颈段食管周向张力的生物力学影响。

DOI：
发表时间：
2023-03-01
期刊：
影响因子：
0
作者：
Lang, Ivan M;Medda, Bidyut K;Shaker, Reza
通讯作者：
Shaker, Reza

A biomechanical response of the esophagus participates in swallowing.

食道的生物力学反应参与吞咽。

DOI：
发表时间：
2023-02-01
期刊：
影响因子：
0
作者：
Lang, Ivan M;Medda, Bidyut K;Kern, Mark;Shaker, Reza
通讯作者：
Shaker, Reza

Effect of inter-swallow interval on striated esophagus peristalsis; a comparative study with smooth muscle esophagus.

吞咽间隔对横纹食管蠕动的影响

DOI：
发表时间：
2023-08
期刊：
影响因子：
3.5
作者：
Edeani, Francis;Sanvanson, Patrick;Mei, Ling;Agrawal, Dilpesh;Kern, Mark;Kovacic, Katja;Shaker, Reza
通讯作者：
Shaker, Reza