The developments of safe and novel methodologies that can be used in vivo in humans are of utmost importance to advance our understanding of the pathophysiology of sensory and motor disorders of the human esophagus. Equally important is the ability to raise key questions that can be answered using novel methodologies in humans where one can study the diseased state as well as find possible targets for pharmacology and surgical therapy. During last funding period we used high frequency ultrasound imaging in a creative fashion to study the following: 1; biomechanics of the wall of the esophagus in relationship to its sensory and motor function, 2; muscle hypertrophy in spastic motor disorders of the esophagus (nutcracker esophagus, diffuse esophageal spasm and achalasia of the esophagus) and 3; longitudinal muscle function and dysfunction of the esophagus in health and disease. Our group has identified novel targets for esophageal sensory and motor dysfunction, i.e., sustained contraction of longitudinal muscles of esophagus as a motor correlate of esophageal pain and hypertrophy of the esophageal musculature in spastic motor disorders of the esophagus using high frequency ultrasound imaging of the esophagus.
The specific aims of our studies during next funding period are to determine: 1, the effects of muscle hypertrophy on the biomechanical properties of the esophageal wall in relationship to esophageal sensation, 2, the incidence of muscle hypertrophy in patients with esophageal symptoms, 3; biomechanical properties of the esophago-gastric junction (EGJ) in normal subjects and patients with muscle hypertrophy, 4; synchrony and asynchrony between circular and longitudinal muscle layers during peristalsis in normal subjects and patients with motor disorders of the esophagus respectively. We believe that our studies will provide new directions to an area of important clinical significance. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK060733-06
Application #
7452451
Study Section
Clinical and Integrative Gastrointestinal Pathobiology Study Section (CIGP)
Program Officer
Hamilton, Frank A
Project Start
2001-12-01
Project End
2011-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
6
Fiscal Year
2008
Total Cost
$270,373
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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