Title: Novel Electrical Impedance Methodology to Understand ?Functional Dysphagia? ABSTRACT Motor activity associated with peristalsis is responsible for the orderly propulsion of swallowed contents in the aboral direction throughout the gastrointestinal (GI) tract. For the bolus to move efficiently through the tubular structure of GI tract, it requires contraction of the segment of the GI tube behind the bolus (ascending contraction) and relaxation in front of the bolus (descending relaxation), which in essence are the two essential elements of a peristaltic reflex (law of intestine). Contraction in the GI tract can be recorded relatively easily using intraluminal pressure or high resolution manometry (HRM). On the other hand, even in year 2015 it is not clear how to record the relaxation limb of the peristaltic reflex during routine clinical esophageal manometry. Normal esophageal dimensions during peristaltic transport are not known. Multiple intraluminal impedance (MII) technique; has been in use for almost 25 years to monitor movements of liquid and air, in both oral and aboral direction in the esophagus. Recent studies from our laboratory show that MII can measure luminal cross section area (CSA) or esophageal distension during peristaltic transport accurately. We propose that esophageal distension is a surrogate marker of descending relaxation of peristalsis and distension can be measured accurately by MII technique. There are 5 major goals of the proposed research. First; to record dynamic changes in the luminal CSA of the esophagus during peristalsis from MII measurements: the method will then be incorporated into a software program that will allow measurement of high resolution distension and high resolution contraction as part of peristalsis using a novel algorithm. We foresee that such a program would become the standard or routine for clinical esophageal motility testing. Second; we propose to test the hypothesis that similar to contraction, the inhibition phase of peristaltic reflex also travels the esophagus in a peristaltic fashion. Third; we will study the relationship between esophageal distension and contraction amplitude, velocity and other parameters of esophageal peristalsis. Fourth; most importantly, we will test the hypothesis that the lack of distension/defective esophageal inhibition is the cause of ?functional dysphagia?. Fifth; finally, we will determine the root cause of poor esophageal distension in patients with functional dysphagia. This proposal is innovative in its application (recording inhibition during routine clinical studies has never been carried out in routine esophageal motility studies). We focus on using MII to quantify luminal distension during bolus transport, and the central role that electrical bio-impedance can play in esophageal motility testing. The proposed project will potentially revolutionize esophageal motility testing, by adding another powerful tool alongside manometry in diagnosing motility disorders related to the abnormalities of the distension/inhibition phase of the peristaltic reflex.

Public Health Relevance

We use a novel impedance methodology along with high resolution manometry to determine the effects of esophageal distension on esophageal motor function. More importantly, we will test a hypothesis that patients with difficulty swallowing or dysphagia symptom have poor distension of the esophagus during peristaltic transport. These patients are currently classified as ?functional dysphagia? and are being mismanaged because the cause of their symptoms is not understood; with proper understanding of their symptoms, it is likely that better treatment strategies will emerge for ?functional dysphagia?.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK109376-02
Application #
9353408
Study Section
Clinical, Integrative and Molecular Gastroenterology Study Section (CIMG)
Program Officer
Hamilton, Frank A
Project Start
2016-09-15
Project End
2021-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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