Tu1848 Distribution of the Acid Sensing Channels Asic-1, Asic-2, 5Enac and PAR-2 Receptors in the Human Esophageal Mucosa

Abstract

Background It is proposed that the presence of esophageal mucosa dilated intercellular spaces (DIS) underlies heartburn in patients with NERD. However, 20% of asymptomatic subjects display DIS in distal esophageal biopsies. Furthermore, esophageal experimental acidification in healthy volunteers provokes DIS, but often without heartburn despite ongoing acid perfusion. These observations suggest that mucosal impairment above and beyond DIS may be relevant in heartburn perception. Functional mucosal integrity in response to acid challenge can be tested in esophageal mucosal biopsies "in vitro" by measuring changes in transepithelial electrical resistance (TER).We aimed to further assess the relationship between presence of DIS, changes in functional esophageal mucosal integrity (TER) and heartburn perception. Methods We took distal esophageal biopsies from patients with and without heartburn. Histological examination for epithelial intercellular space diameter (ISD) was done using light microscopy by taking 50 random measurements at several levels from the basal epithelial layers for each biopsy. DIS was declared at above the 95% CI for normal values as previously published (.0.72μm). We identified 11 subjects with DIS (4 with predominant daily troublesome heartburn, 7 with predominant dyspepsia and no heartburn). Biopsies were placed in mini-Ussing chambers, and baseline TER was measured. The luminal aspect of the biopsy was then exposed for 30min to an acidic solution (pH2+1mg/ml pepsin+1mM taurodeoxycholate). During exposures, % changes in TER relative to baseline were analyzed. Results The mean ISD in all subjects was 0.94μm (range 0.74-1.18μm). There was no significant difference in ISD (0.95 vs. 0.91μm) or baseline TER (144 vs. 165V.cm2) between predominant heartburn and predominant dyspepsia groups. Despite the pre-existing DIS in all subjects, 30 minutes acid exposure was able to induce a further reduction in TER (-23.0% change from baseline, p,0.01). The reduction in TER was greater in subjects with predominant reflux vs. those with predominant dyspepsia (-40.4±10.3% vs. -11.2±3.7%, p=0.01). Conclusion In subjects with pre-existing DIS with and without hearburn, trans-epithelial electrical resistance can be further impaired with in vitro acid exposure, suggesting that the mechanism for acid-induced mucosal integrity impairment is not limited to DIS. Furthermore, acid-induced functional integrity impairment was greater in patients with heartburn. This difference in mucosal behaviour in the presence of acid suggests that other mechanisms beyond DIS might be needed to further stimulate afferent nerves in heartburn generation.