Gaviscon double action protects against acid-induced increases in oesophageal mucosal permeability ex vivo

Introduction

Gastro-oesophageal reflux disease (GORD) is characterised by symptoms (most commonly heartburn) caused by exposure of the oesophageal mucosa to gastric contents. Usually, the macroscopic appearance of the mucosa in GORD is normal (non-erosive reflux disease, NERD). However, the oesophageal mucosa in NERD has microscopic dilated intercellular spaces (where the gaps between epithelial cells are wider), suggestive of impaired barrier function. This increased mucosal permeability is likely to allow permeation of refluxate to deeper layers of the mucosa where it can stimulate nociceptive nerves. Mucosal permeability can be measured by way of transepithelial electric resistance (TER) of biopsies in an Ussing chamber, and increased permeability (reduced TER) is rapidly induced by exposure of the biopsies to acidic solutions. Alginate solutions are used in GORD primarily for their gastric ‘raft’ forming and antacid properties. However, alginate solutions may also have a therapeutic action via oesophageal mucosal protection properties. We tested the ability of topically applied Gaviscon Double Action to reduce impairment of mucosal integrity caused by reflux-like solutions in an Ussing chamber model.

Methods

24 patients having gastroscopy for clinical reasons were recruited at the Royal London Hospital. From each patient, mucosal biopsies were taken from the distal oesophagus, 3–5 cm above the z-line. The lumen of each biopsy was protected for 5 minutes with Gaviscon Double Action (GDA), or Gaviscon Placebo (GP, a solution of similar viscosity to GDA but without alginates). Protectant was washed off, biopsies were mounted in an Ussing chamber filled with pH7.4 Krebs-Henseleit solution, and baseline TER was measured. Next, the solution in the luminal chamber was replaced with a reflux-like solution of pH2 Krebs-Henseleit solution + 1mM deoxycholic acid + 1mg/mL porcine pepsin for 30mins. Percentage change of TER from baseline at 30mins was analysed by paired t-test.

Results

Acid-induced reduction of TER was less in the GDA group than in the GP group (mean 29.9% ± 16.0% vs 40.4% ± 15.0%; p = 0.0015). Data is represented in figure 1 as% change in oesophageal biopsy TER in response to luminal acid exposure following pre-treatment with test solutions.

Conclusions

When pre-applied to human oesophageal mucosal biopsies, GDA (containing alginate) is more effective than GP (which does not) at preventing the effects of acid exposure on oesophageal epithelial permeability. Penetration of toxic refluxate into the epithelium of the oesophagus is important in both pain perception and inflammation in GORD, via receptor-mediated mechanisms and induction of epithelial cell damage. Mucosal topical protection such as that provided by GDA could as a useful therapeutic tool in the treatment of GORD.