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Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus
  1. Ricard Farré1,2,
  2. Fernando Fornari1,
  3. Kathleen Blondeau1,
  4. Michael Vieth3,
  5. Rita De Vos4,
  6. Raf Bisschops5,
  7. Veerle Mertens1,
  8. Ans Pauwels1,
  9. Jan Tack1,5,
  10. Daniel Sifrim1,6
  1. 1Center for Gastroenterological Research, Catholic University Leuven, Belgium
  2. 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, (Ciberehd), Instituto de Salud Carlos III, Spain
  3. 3Department of Pathology, Institute of Pathology, Bayreuth Hospital, Bayreuth, Germany
  4. 4Department of Pathology, University Hospital Gasthuisberg, Catholic University Leuven, Belgium
  5. 5Division of Gastroenterology, University Hospital Gasthuisberg, Catholic University Leuven, Belgium
  6. 6Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK
  1. Correspondence to Dr Daniel Sifrim, The Wingate Institute of Neurogastroenterology, 26 Ashfield Street, London E1 2AJ, UK; d.sifrim{at}


Background Oesophageal mucosa dilated intercellular spaces (DIS) may be important for symptom perception in non-erosive reflux disease (NERD). Patients with NERD might have DIS even in the proximal oesophagus. We aimed to assess the effect of oesophageal perfusions with acid and weakly acidic solutions on ‘exposed’ and ‘non-exposed’ oesophageal mucosa and its relationship to symptoms in healthy subjects.

Methods 14 healthy volunteers underwent upper gastrointestinal endoscopy with biopsies at 3 and 13 cm proximal to the oesophagogastric junction (OGJ). In following sessions, subjects received 30 min perfusions with neutral, weakly acidic, acidic and acidic-bile acid solutions at 5 cm above the EGJ (separated 4 weeks). Biopsies were taken 20 min after perfusions. Electron microscopy was used to measure DIS. Subjects scored heartburn during perfusions using a visual analogue scale.

Results (1) Oesophageal perfusion with acid solutions, with or without bile acids, provoked DIS in the ‘exposed’ oesophageal mucosa; (2) oesophageal perfusion with weakly acidic solutions provoked identical changes to those observed after perfusion with acid solutions; (3) distal oesophageal perfusions not only provoked changes in the ‘exposed’ but also in the more proximal ‘non-exposed’ mucosa; and (4) in spite of the presence of perfusion-induced DIS, most healthy subjects did not perceive heartburn during the experiments.

Conclusions The human oesophageal mucosa is very sensitive to continuous exposure with acidic and weakly acidic solutions. In spite of the presence of intraluminal acid and DIS, healthy subjects did not experience heartburn, suggesting that NERD patients should have other critical factors underlying their symptoms.

  • Dilated intercellular spaces
  • non-erosive reflux disease
  • weakly acidic
  • human
  • acid
  • gastroesophageal reflux disease
  • non-cardiac chest pain

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  • Funding This work was partially funded by Astra Zeneca Sweden which did not participate in the study design, in the collection, analysis or interpretation of data. RF is a postdoctoral fellow, FWO (Research Foundation, Flanders).

  • Competing interests None.

  • Ethics approval This study was approved by the Ethical Committee of the Catholic University Leuven on 26 October 2006, and performed in accordance with the Declaration of Helsinki.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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