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: 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
• 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

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.

食管运动功能是吞咽和气道保护的关键参与者，但是这些功能 尚未在近端/横纹食管（St.eso）中系统地研究它 气道及其功能障碍引起的攻击风险。我们的初步研究揭示了重要的新发现 在导致要测试的假设发展的圣eso功能的临床相关性上有很大的相关性 在此提案中。该提案有两个具体的目标。 在特定目的中，我将表征圣eso退化运动功能及其通过咽部调节 吞咽生物力学。我们将测试以下假设1）St.So。运动功能构成四个不同的 与喉部高升高相关的退化偏移相关的成分：a。增加壁张力 符合其前纵横旅行的大小，b。在 UES开放，c。蠕动 /推注转运的功能，随着降临和d。继续蠕动的休息 位置。 2。圣eso运动功能的组件与咽部相关，可以通过咽部调节 生物力学和相关压力。 SA 1A：在健康和患者的志愿者中，我们将确定和表征：i。非pristaltic和 St.eso运动功能的蠕动组件及其与咽相生物力学的关系， ii。实验增强和减少圣eso咽生物力学的影响。运动功能，iii。 St.Eso peristals参数及其按推注类型，体积，身体位置和年龄的调节 ART并发HRM/阻抗测压/数字视频荧光镜和我们的新型实验设备。 SA 1B：在我们的猫科动物模型中，我们将：i。表征上喉旅行之间的关系 吞咽过程中St.Eso电动机功能的组件，即peristaltic 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 机制包括ENS和CNS神经反射控制以及St.eso的生物力学特性。 在特定目标2中，我们将描述圣eso。气道保护功能及其与 UES和食管继发性蠕动。我们将检验以下假设：1）St.So。回应 回流事件通过堵塞限制UES压力的腔内的腔内蠕动独立于继发性蠕动 回复。 2）这个回应是我。依赖年龄，与回流的类型，数量和速度有关 和II。在疾病状态下，与UES反应不存在。 SA 2A：在健康和患者的志愿者中，我们将描述圣eso。对我的回应。生理 反流和ii。模拟回流事件（具有各种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对模拟的一致性的响应 和生理回流事件，ii。 St.eso的功能关系。对继发性蠕动的反应。

项目成果

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: 10.1152/japplphysiol.00667.2022
• 发表时间: 2023
• 期刊: Journal of applied physiology (Bethesda, Md. : 1985)
• 作者: Lang,IvanM;Medda,BidyutK;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: 10.1152/ajpgi.00219.2022
• 发表时间: 2023
• 期刊: American journal of physiology. Gastrointestinal and liver physiology
• 作者: Lang,IvanM;Medda,BidyutK;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: 10.1111/nmo.14608
• 发表时间: 2023
• 期刊: Neurogastroenterology and motility
• 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