The biomechanical properties of the esophagus have relevance to its motor and sensory function. These properties have been studied in the animals and humans by several investigators using various techniques. However, there are limitations with each of these techniques. We have developed a novel system of balloon ultrasonography that measures esophageal pressure, radius and wall thickness simultaneously, in vivo, in humans. Our technique, therefore, allows accurate measurement of the wall stress, strain and elastic modulus (wall rigidity) on a continuous time basis. Our preliminary data show that in normal subjects there is a close temporal correlation between increase in intraluminal pressure and esophageal wall thickness, which allows the esophagus to maintain a low wall stress. Patients with motility disorders of the esophagus have a thicker esophageal muscularis propria compared to normal subjects. We hypothesize that difference in the biomechanical properties of the esophageal wall between normal subjects and patients is the reason for impaired esophageal transport and dysphagia in patients with motility disorders of the esophagus. The current understanding is that hypersensitivity of the esophagus is the cause of esophageal pain. Patients with presumed esophageal pain respond to distension of the esophagus at lower balloon volumes than normal subjects. The site of esophageal hypersensitivity may be at either the peripheral (esophageal wall) or at the central level (CNS). The latter is currently the favored site. The differences in the biomechanical properties of the esophageal wall in patients and normal subjects may result in different wall stress and strain in response to the same volume of distension. We hypothesize that differences in the biomechanical properties of the esophagus may be the reason for a hypersensitive esophagus.
The specific aims of our studies are: 1: In vitro validation of the novel technique of balloon-ultrasonography. 2: To determine biomechanical properties of the esophagus in normal human subjects using balloon ultrasonography and to determine the relationship between esophageal pain and its biomechanical properties. 3: To define the abnormalities of muscularis propria thickness in patients with primary motility disorders of the esophagus. 4: To determine the biomechanical properties of the esophageal wall in patients with a normal and thick muscularis propria and its relationship to esophageal hypersensitivity. 5: To study biomechanics of the esophageal wall in patients with esophageal dysphagia. We believe that our observations have important implications in understanding the mechanisms of esophageal motor and sensory function in healthy and diseased states. Furthermore, the principles discussed in the esophagus may be applicable to the understanding of visceral hypersensitivity seen in irritable bowel syndrome and other functional disorders of the GI tract.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK060733-03S1
Application #
7107070
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Hamilton, Frank A
Project Start
2002-09-01
Project End
2006-06-30
Budget Start
2005-08-15
Budget End
2006-06-30
Support Year
3
Fiscal Year
2005
Total Cost
$103,078
Indirect Cost
Name
Veterans Medical Research Fdn/San Diego
Department
Type
DUNS #
933863508
City
San Diego
State
CA
Country
United States
Zip Code
92161
Mittal, Ravinder K (2018) Is the Lower Esophageal Sphincter Tone Related to a Gas? Cell Mol Gastroenterol Hepatol 5:239-240
Zifan, Ali; Sun, Catherine; Gourcerol, Guillaume et al. (2018) Endoflip vs high-definition manometry in the assessment of fecal incontinence: A data-driven unsupervised comparison. Neurogastroenterol Motil 30:e13462
Babaei, Arash; Mittal, Ravinder (2018) Cholecystokinin induces esophageal longitudinal muscle contraction and transient lower esophageal sphincter relaxation in healthy humans. Am J Physiol Gastrointest Liver Physiol 315:G734-G742
Park, Subum; Zifan, Ali; Kumar, Dushyant et al. (2018) Genesis of Esophageal Pressurization and Bolus Flow Patterns in Patients With Achalasia Esophagus. Gastroenterology 155:327-336
Zifan, A; Jiang, Y; Mittal, R K (2017) Temporal and spectral properties of esophageal mucosal blood perfusion: a comparison between normal subjects and nutcracker esophagus patients. Neurogastroenterol Motil 29:
Zifan, Ali; Kumar, Dushyant; Cheng, Leo K et al. (2017) Three-Dimensional Myoarchitecture of the Lower Esophageal Sphincter and Esophageal Hiatus Using Optical Sectioning Microscopy. Sci Rep 7:13188
Mittal, Ravinder K; Zifan, Ali; Kumar, Dushyant et al. (2017) Functional morphology of the lower esophageal sphincter and crural diaphragm determined by three-dimensional high-resolution esophago-gastric junction pressure profile and CT imaging. Am J Physiol Gastrointest Liver Physiol 313:G212-G219
Jiang, Yanfen; Mittal, Ravinder K (2016) Low esophageal mucosal blood flow in patients with nutcracker esophagus. Am J Physiol Gastrointest Liver Physiol 310:G410-6
Lee, Robert H; Korsapati, Hariprasad; Bhalla, Vikas et al. (2016) Esophageal Submucosal Injection of Capsaicin but Not Acid Induces Symptoms in Normal Subjects. J Neurogastroenterol Motil 22:436-43
Patel, Nirali; Jiang, Yanfen; Mittal, Ravinder K et al. (2015) Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation. Am J Physiol Gastrointest Liver Physiol 309:G360-7

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