Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana

Abstract

Esophageal motor abnormalities, as well defects in the lower esophageal sphincter, are common aspects of gastroesophageal reflux disease. The objective of this work is to develop a model of non-erosive gastroesophageal reflux in rats by acute exposure of the esophagus to solutions that simulate gastric content and evaluate the repercussions on contractility through isometric recordings obtained from esophagus and gastroesophageal junction (GEJ) samples by a digital acquisition system. Esophageal segments mounted in the circular direction that remained for 30 min in contact with Tyrode pH 1 containig pepsin and taurodeoxycholate (TDCA) showed lower contractile responses to increasing concentrations of KCl, CCh and EFS (Electric Field Stimulation) when compared to segments exposed to the control solution (Tyrode pH 7.4), while longitudinal segments showed hiporesponsiveness only for the cholinergic stimulus. Initial minutes, of the evaluation of the esophageal mucosa revealed a decrease in the transepithelial electrical resistance (TER) of segments exposed to the same acid challenge in comparison to the control solution. The circular esophagus in contact for 10 min with the acidic solution showed lower values of contractions evoked by KCl, CCh and EFS when compared to the control exposure, whereas longitudinal esophageal strips did not present significant alterations. The contractile evaluation performed on GEJ rings did not show significant differences in responses to KCl, CCh or EFS stimuli when we varied both the pH and time between the groups. Experimental protocols revealed similarities in the relaxant response in tissues exposed to the control or acid solution caused by increasing concentrations of sodium nitroprusside, isoproterenol or serotonin in the esophagus preparations, whereas segments of GEJ relaxed more when previous exposed to acid contact. The topical application of alginate suspension in esophageal mucosa samples was able to improve TER damage caused by exposure to acidic challenge. The contractility of esophageal muscle samples was also improved, but the responsiveness of GEJ segments was lower with previous application of the formulation. Esophagus filled only with acidic solution (pH 1) for 30 min had no significant change in the contractile response induced by EFS, an effect observed only with the combination of this solution with pepsin and TDCA. The present model reveals motor alterations of the esophagus and GEJ of rats compatible with phenomena already seen in more aggressive models and allows other important investigations for the disease.