Although much new information about normal esophageal motor function has accrued during the past several decades, many important questions remain unanswered. This grant proposal represents a comprehensive intra- disciplinary, intradepartmental. approach to investigating esophageal motor function In normal subjects, patients with gastroesophageal reflux disease and patients with a spectrum of esophageal motor disorders. Studies will also be done in laboratory animals consisting of the dog, cat and opossum. Each animal model is carefully selected for a specific purpose. The specific protocols tall into three general, but interrelated categories: (1) gastro-esophageal reflux disease, (2) esophageal motor physiology and bolus transport in healthy humans and experimental animals, and (3) studies of esophageal motility disorders in humans and animal models of abnormal esophageal motility. Investigations will utilize videofluoroscopy of barium swallows, intraluminal manometry, esophageal transducers, esophageal marker measurements, esophageal pH recording and diaphragmatic electromyography (EMG). The dog exhibits spontaneous episodes of acid, gastroesophageal reflux and belch and can be studied while awake or minimally sedated. Studies are proposed to determine whether transient diaphragmatic crural relaxation occurs concurrent with the transient lower esophageal sphincter (LES) relaxation that underlie the majority gastroesophageal reflux (GER) episodes in humans as well as dogs, a particular emphasis will be given to glucidating the mechanisms that permit regurgitation of acid above the upper esophageal sphincter (UES) into the pharynx In humans. Another major area of interest is quantitation and modeling of the pressure-flow kinetics and physical principles associated with peristaltic transport of a liquid esophageal bolus. This project will involve studies of esophageal bolus transport in the cat and opossum. The cat was selected because its LES lies within the diaphragmatic hiatus, as is the case with humans. The opossum has smooth muscle in the distal two-thirds of the esophagus, a distribution identical to that of humans. Studies of esophageal physiology will focus largely on the role of the longitudinal esophageal muscle in esophageal peristalsis, bolus transport and LES opening. Studies in patients with esophageal motility disorders and animal models of abnormal motility (stimulation of diffuse esophageal spasm and idiopathic achalasia) will beater define the pathogenesis of abnormal motility and also provide data for the modeling of abnormal bolus transport.
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