Hiatal Dysfunction in Achalasia Esophagus

贲门失弛缓症食管裂孔功能障碍

• 批准号: 10421810
• 负责人: RAVINDER K. MITTAL
• 金额: $ 66.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10421810
• 关键词: 3-Dimensional; Achalasia; Anatomy; Animal Model; Barrett Esophagus; Body Weight decreased; Case-Control Studies; Catheters; Cells; Chest Pain; Chronic; Deglutition Disorders; Disease; Electromyography; Esophageal Adenocarcinoma; Esophageal Diseases; Esophageal achalasia; Esophageal motility disorders; Esophagogastric Junction; Esophagus; Fibrosis; Functional disorder; Generations; Goals; Health; Heartburn; Hernia; Herpes Simplex Infections; Histologic; Human; Image; Impairment; Inferior esophageal sphincter structure; Infiltration; Inflammation; Inflammatory; Injury; Journals; Laboratories; Lymphocyte; Magnetic Resonance Imaging; Malignant - descriptor; Manometry; Mechanics; Medicine; Methodology; Microscopic; Motor Neurons; Muscle; Myenteric Plexus; Nature; New England; Obstruction; Pathogenesis; Pathologic; Pathology; Patients; Peristalsis; Play; Precancerous Conditions; Radiology Specialty; Reflux; Relaxation; Research Personnel; Resolution; Respiratory Diaphragm; Role; Skeletal Muscle; Slide; Smooth Muscle; Specimen; Sphincter; Structure; Structure-Activity Relationship; Symptoms; Techniques; Testing; Vertebral column; Virus Diseases; Weight; X-Ray Computed Tomography; autoimmune inflammation; experimental study; improved; motility disorder; motor disorder; muscle hypertrophy; nerve supply; novel; novel strategies; pressure

Project Summary: The sphincter mechanism at the lower end of the esophagus, lower esophageal sphincter plays a major role in the pathophysiology of esophageal motor disorders. An incompetent sphincter leads to reflux disease (weak sphincter or too much relaxation) and overtly competent sphincter (too little relaxation) leads to achalasia esophagus and possibly other motor disorders of the esophagus. Exact understanding of the lower esophageal sphincter has defied generations of investigators. Our studies, over a span of more than 35 years have revealed that the lower esophageal sphincter mechanism consists of 2 components, smooth muscle LES and skeletal muscle crural diaphragm (CD). Using “state of the art” techniques such as 3D-high resolution manometry along with static and dynamic CT scan imaging, our preliminary studies suggests that the crural diaphragm which forms the esophageal hiatus may play a crucial role in the pathogenesis of achalasia esophagus, a major motility disorder of the esophagus. The specific goals of the proposal are to define: 1) the 3D pressure profile of the EGJ in achalasia esophagus: extend our preliminary findings of anatomical and functional abnormalities of crural diaphragm in patients with achalasia esophagus, to study the crural diaphragm structure and function using MR imaging and crural diaphragm EMG recordings respectively. 2) To demonstrate lack of sliding, or in other words a tight anchoring between the LES and crural diaphragm in patients with achalasia esophagus. 3) We propose to study the effect of spine disc injury on the structure and function of the crus of diaphragm/hiatal muscle in an animal model: We will test a novel hypothesis that injury to the lumbar spine leads to pathological changes in the structure and function of the crus diaphragm muscle.

项目摘要：食道下端的括约肌机制，下食道括约肌 在食道运动障碍的病理生理学中起重要作用。括约肌功能不全会导致 反流病(括约肌无力或过度松弛)和明显强健的括约肌(松弛过少) 导致失弛缓症、食道失弛缓症以及其他可能的食道运动障碍。准确地理解 下食道括约肌已经挑战了几代研究人员。我们的研究，在超过一段时间里 35年的研究表明，下食道括约肌机制由2个部分组成，顺畅 肌肉LES和骨骼肌脚隔膜(CD)。使用“最先进的”技术，如3D-High 分辨率测压以及静态和动态CT扫描成像，我们的初步研究表明 形成食道裂孔的脚横隔膜可能在食道裂孔的发病机制中起重要作用。 食道失弛缓症，一种主要的食道动力障碍。该提案的具体目标是 定义：1)贲门失弛缓症食道中EGJ的3D压力分布：扩展我们的初步发现 目的：探讨幽门失弛缓症患者脚隔膜的解剖和功能异常。 分别用磁共振成像和小腿隔膜肌电记录研究小腿隔膜的结构和功能。 2)以显示没有滑动，或者换句话说，在LES和脚横隔膜之间没有紧密锚定 食道失弛缓症患者。3)我们建议研究脊柱间盘损伤对结构和功能的影响。 横隔肌/裂孔肌脚在动物模型中的功能：我们将检验一种新的假设 对腰椎的损伤会导致小腿横隔肌结构和功能的病理改变。