ESOPHAGEAL MOTOR FUNCTION IN HEALTH AND DISEASE

Summary

Principal Investigator: R Shaker
Affiliation: Medical College of Wisconsin
Country: USA
Abstract: The overall objective of this grant is an in-depth investigation of esophageal function in health and disease as it relates to gastroesophago- pharyngeal reflux and aspiration. Gastroesophageal reflux disease is the most common malady of the esophagus. It is estimated that 7-10% of the US population suffers from various degrees of this disease. This translates into a significant burden on health care resources. However, complications of reflux disease induced outside the esophagus; namely in the aerodigestive and airway tracts, are now becoming increasingly recognized. For example, it is estimated that 4- 10% of laryngeal diseases seen in ENT clinics are associated with reflux disease. Our specific objectives are: A) To determine the patho- physiological basis of supraesophageal complications of gastroesophageal reflux disease. This section will include: characterization and quantification of gastroesophago-pharyngeal reflux with special emphasis on the association between reflux-induced esophageal and supraesophageal lesions; 2) characterization of the defensive mechanisms against aspiration of gastroesophago-pharyngeal reflux, including a) characterization of the mechanisms of esophagopharyngeal reflux of gastric acid in controls and patients with reflux laryngitis, and b) defining the airway protective mechanisms against pharyngolaryngeal reflux of gastric content in controls and GERD patients. The hypothesis that patients with reflux-induced laryngeal lesions have abnormalities of one or more of the airway protective mechanisms against reflux of gastric content will be tested. These include abnormalities of lower esophageal sphincter function, esophageal body motor response to distension, esophagoglottal closure reflex, UES resting tone and esophago-UES contractile reflex, pharyngo-UES contractile reflex and activation of pharyngeal-induced swallows, and pharyngoglottal closure reflex. B) Neural mechanisms of esophageal sensory motor function in relation to gastroesophago-pharyngeal reflux will be investigated. We will l) determine, in a feline model, the brainstem and reflex control of airway protective mechanisms, 2) identify the cerebral cortical regions involved in esophageal viscero sensation, and 3) characterize the effect of inhibitory influence of pharyngeal stimulation on esophageal peristalsis and bolus transport, LES tone and gastroesophageal reflux in normal controls and GERD patients and we will expand our mathematical modeling effort to include the airway protective reflexes during gastroesophageal reflux. Individual, but interrelated protocols are proposed to achieve our objectives and will be executed by our multidisciplinary, interdepartmental team.
Funding Period: 1979-07-01 - 2001-01-31
more information: NIH RePORT

Top Publications

  1. ncbi Response properties of the brainstem neurons of the cat following intra-esophageal acid-pepsin infusion
    B K Medda
    MCW Dysphagia Institute and Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
    Neuroscience 135:1285-94. 2005
  2. doi Manometric evidence for a phonation-induced UES contractile reflex
    Lilani Perera
    Division of Gastroenterology and Hepatology, Froedtert Hospital Medical College of Wisconsin Dysphagia Institute, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA
    Am J Physiol Gastrointest Liver Physiol 294:G885-91. 2008
  3. doi Fatigue analysis before and after shaker exercise: physiologic tool for exercise design
    Kevin T White
    Department of Physical Medicine and Rehabilitation PMR, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
    Dysphagia 23:385-91. 2008
  4. pmc Alterations in N-methyl-D-aspartate receptor subunits in primary sensory neurons following acid-induced esophagitis in cats
    Banani Banerjee
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Am J Physiol Gastrointest Liver Physiol 296:G66-77. 2009
  5. ncbi Intramucosal distribution of WNT signaling components in human esophagus
    Irshad Ali
    Division of Gastroenterology and Hepatology, MCW Dysphagia Institute, Digestive Disease Center, Medical Collegeof Wisconsin, Milwaukee, WI 53226, USA
    J Clin Gastroenterol 43:327-37. 2009
  6. pmc Differential effects of transient receptor vanilloid one (TRPV1) antagonists in acid-induced excitation of esophageal vagal afferent fibers of rats
    S Peles
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Neuroscience 161:515-25. 2009
  7. pmc Effect of esophageal acid exposure on the cortical swallowing network in healthy human subjects
    Mark Kern
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Physiol Gastrointest Liver Physiol 297:G152-8. 2009
  8. pmc Terminating motor events for TLESR are influenced by the presence and distribution of refluxate
    Shiko Kuribayashi
    Dysphagia Institute, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Physiol Gastrointest Liver Physiol 297:G71-5. 2009
  9. doi Effect of systemic alcohol and nicotine on airway protective reflexes
    Kulwinder S Dua
    Department of Gastroenterology and Hepatology, MCW Dysphagia Institute, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Gastroenterol 104:2431-8. 2009
  10. doi Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus
    Adeyemi Lawal
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Am J Physiol Gastrointest Liver Physiol 294:G787-94. 2008

Scientific Experts

  • Banani Banerjee
  • R Shaker
  • I M Lang
  • Richard Effros
  • Kevin T White
  • Candy Hofmann
  • Mark Kern
  • Kulwinder S Dua
  • Tanya Rittmann
  • Adeyemi Lawal
  • Shiko Kuribayashi
  • Linda Tatro
  • Lilani Perera
  • Osamu Kawamura
  • Muhammad Aslam
  • Shailesh Bajaj
  • Jasmohan S Bajaj
  • B K Medda
  • Irshad Ali
  • S Peles
  • Krisna Chai
  • J N Sengupta
  • E Bardan
  • Eytan Bardan
  • George Haasler
  • Rose Franco
  • Muhammad Hafeezullah
  • Zhihong Zhang
  • Ronald J Darling
  • Yue Zheng
  • Howard Jacob
  • Rajesh Santharam
  • David Knuff
  • Parvaneh Rafiee
  • Sri Naveen Surapaneni
  • A Lehmann
  • Christopher Johnson
  • Benson T Massey
  • Syed Q Hussaini
  • Rachel Mepani
  • Matt Verber
  • Syed Hussaini
  • Andrzej Jesmanowicz
  • Arthi Sanjeevi
  • Stephen Antonik
  • Jianxiang Liu
  • Caryn Easterling
  • Ronald C Arndorfer
  • B T Massey
  • S Torrico
  • R C Arndorfer
  • Safwan Jaradeh
  • M Kern

Detail Information

Publications21

  1. ncbi Response properties of the brainstem neurons of the cat following intra-esophageal acid-pepsin infusion
    B K Medda
    MCW Dysphagia Institute and Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
    Neuroscience 135:1285-94. 2005
    ..Results also indicate that spinal pathway does not contribute to sensitization of brainstem neurons...
  2. doi Manometric evidence for a phonation-induced UES contractile reflex
    Lilani Perera
    Division of Gastroenterology and Hepatology, Froedtert Hospital Medical College of Wisconsin Dysphagia Institute, 9200 W Wisconsin Ave, Milwaukee, WI 53226, USA
    Am J Physiol Gastrointest Liver Physiol 294:G885-91. 2008
    ..UESP increase due to this reflex is significantly higher than that of the distal esophagus, LES, and stomach. The phonation-induced UESP increase is influenced by sex...
  3. doi Fatigue analysis before and after shaker exercise: physiologic tool for exercise design
    Kevin T White
    Department of Physical Medicine and Rehabilitation PMR, Medical College of Wisconsin, Milwaukee, WI, 53226, USA
    Dysphagia 23:385-91. 2008
    ....
  4. pmc Alterations in N-methyl-D-aspartate receptor subunits in primary sensory neurons following acid-induced esophagitis in cats
    Banani Banerjee
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA
    Am J Physiol Gastrointest Liver Physiol 296:G66-77. 2009
    ..It is possible that these changes may in part contribute to esophageal hypersensitivity observed in reflux esophagitis...
  5. ncbi Intramucosal distribution of WNT signaling components in human esophagus
    Irshad Ali
    Division of Gastroenterology and Hepatology, MCW Dysphagia Institute, Digestive Disease Center, Medical Collegeof Wisconsin, Milwaukee, WI 53226, USA
    J Clin Gastroenterol 43:327-37. 2009
    ....
  6. pmc Differential effects of transient receptor vanilloid one (TRPV1) antagonists in acid-induced excitation of esophageal vagal afferent fibers of rats
    S Peles
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Neuroscience 161:515-25. 2009
    ..The use of TRPV1 antagonists could be an alternative to the traditional symptoms-based treatment of chronic acid reflux and esophageal hypersensitivity...
  7. pmc Effect of esophageal acid exposure on the cortical swallowing network in healthy human subjects
    Mark Kern
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Physiol Gastrointest Liver Physiol 297:G152-8. 2009
    ..05). The precuneus showed no significant change. We concluded that subliminal esophageal acid stimulation has a potentiating effect on the cortical swallowing network in healthy individuals...
  8. pmc Terminating motor events for TLESR are influenced by the presence and distribution of refluxate
    Shiko Kuribayashi
    Dysphagia Institute, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Physiol Gastrointest Liver Physiol 297:G71-5. 2009
    ..We concluded that, in healthy recumbent subjects, the most common TLESR-termination event is a secondary contraction, rather than PP. Presence and distribution of the refluxate is a major influence on the type of terminating contraction...
  9. doi Effect of systemic alcohol and nicotine on airway protective reflexes
    Kulwinder S Dua
    Department of Gastroenterology and Hepatology, MCW Dysphagia Institute, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Gastroenterol 104:2431-8. 2009
    ..It is not known whether this is a local effect of smoking on the pharynx or a systemic effect of nicotine. The aim of this study was to elucidate the effect of systemic alcohol and nicotine on PUCR and RPS...
  10. doi Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus
    Adeyemi Lawal
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Am J Physiol Gastrointest Liver Physiol 294:G787-94. 2008
    ....
  11. ncbi Airway responses to esophageal acidification
    Ivan M Lang
    Medical College of Wisconsin Dysphagia Institute, Divisions of Gastroenterology and Hepatology and Pulmonary Medicine, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
    Am J Physiol Regul Integr Comp Physiol 294:R211-9. 2008
    ..Given the buffering capabilities of mucus, esophageal acidification activates appropriate physiological responses that may act to neutralize gastroesophageal reflux that reaches the larynx, pharynx, or lower airways...
  12. ncbi Effect of reflux-induced inflammation on transient receptor potential vanilloid one (TRPV1) expression in primary sensory neurons innervating the oesophagus of rats
    B Banerjee
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Neurogastroenterol Motil 19:681-91. 2007
    ..The over expression of TRPV1 may contribute to oesophageal hypersensitivity observed in gastro-oesophageal reflux disease (GORD)...
  13. pmc The effects of volatile salivary acids and bases on exhaled breath condensate pH
    Richard M Effros
    Los Angeles Biomedical Research Institute at Harbor UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502 2064, USA
    Am J Respir Crit Care Med 173:386-92. 2006
    ..Recent studies have reported acidification of exhaled breath condensate (EBC) in inflammatory lung diseases. This phenomenon, designated "acidopnea," has been attributed to airway inflammation...
  14. ncbi Influence of sleep stages on esophago-upper esophageal sphincter contractile reflex and secondary esophageal peristalsis
    Jasmohan S Bajaj
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Gastroenterology 130:17-25. 2006
    ..Our aim was to study EUCR and 2P elicitation in "awake" state, stage II, slow-wave (stage III/IV), and rapid eye movement (REM) sleep...
  15. ncbi Effect of aging on bolus kinematics during the pharyngeal phase of swallowing
    Eytan Bardan
    Division of Gastroenterology and Hepatology, Dysphagia Institute, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
    Am J Physiol Gastrointest Liver Physiol 290:G458-65. 2006
    ..Among these differences were the absence of hypopharyngeal bolus acceleration and a significant increase in the trans-sphincteric pressure gradient in the elderly...
  16. ncbi Radial asymmetry of the upper oesophageal sphincter pressure profile: fact or artefact
    E Bardan
    Chaim Sheba Medical Center, Tel Hashomer, Israel
    Neurogastroenterol Motil 18:418-24. 2006
    ....
  17. ncbi Impedance signature of pharyngeal gaseous reflux
    Osamu Kawamura
    Department of Endoscopy and Endoscopic Surgery, Gunma University Hospital, Maebashi, Japan
    Eur J Gastroenterol Hepatol 19:65-71. 2007
    ..Pharyngeal impedance changes induced by various pharyngeal reflux events have not been characterized...
  18. ncbi Performance and optimal technique for pharyngeal impedance recording: A simulated pharyngeal reflux study
    Muhammad Aslam
    MCW Dysphagia Institute, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
    Am J Gastroenterol 102:33-9. 2007
    ..We evaluated the ability of the impedance sensor for detection of various volumes of intrapharyngeal infusate at two sites and in two subject positions...
  19. ncbi Safety and feasibility of evaluating airway-protective reflexes during sleep: new technique and preliminary results
    Kulwinder S Dua
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
    Gastrointest Endosc 65:483-6. 2007
    ..The airway is vulnerable to aspiration during sleep. The integrity of aerodigestive-protective reflexes during sleep has not been studied previously because of a lack of adequate techniques...
  20. ncbi Gastroesophageal reflux disease: beyond mucosal injury
    Reza Shaker
    Division of Gastroenterology and Hepatology, Department of Medicine, MCW Digestive Disease Center, Medical College of Wisconsin, Milwaukee, WI 53223, USA
    J Clin Gastroenterol 41:S160-2. 2007
    ....
  21. doi Altered expression of P2X3 in vagal and spinal afferents following esophagitis in rats
    Banani Banerjee
    Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Histochem Cell Biol 132:585-97. 2009
    ..Changes in P2X(3) expression in vagal and spinal sensory neurons may contribute to esophageal hypersensitivity following acid reflux-induced esophagitis...