Experimental studies on barriers of the esophageal mucosa

Reflux esophagitis is the multifactorial result of the failing of protective barriers and the aggressive assault on the esophageal epithelium by gastric contents entering the esophagus. The three main lines of defense against reflux are: the antireflux barriers, the luminal acid clearance and the epithelium itself. Plasma membranes, junctional complexes, intercellular substances, as well as cell renewal are important components of the epithelial resistance. This Thesis elucidates some defense mechanisms in the epithelium utilizing the following methods: The presence of several glycoconjugates in the esophageal epithelium was determined by histochemical staining with lectins. These studies were carried out in normal, healthy mammals, as well as in rabbits with acute mucosal damage caused by the perfusion of the esophagus with pepsin/HCl. In parallel, early acid induced changes of epithelial integrity were studied by measuring the transmural electrical resistance of the esophagus, using cable analysis. A chronic reflux esophagitis model was developed in cats by transection of the muscle fibers in the region of the gastroesophageal junction, thereby disabling the lower esophageal sphincter. The resulting changes on the esophageal epithelium were studied by light microscopy. Finally, by continuous labeling of dividing cells with 3H-thymidine, cell turnover times of the esophageal epithelium were determined in normal rats, as well as in rats with hypergastrinemia for up to 9 days. This condition was achieved by continuous subcutaneous infusion of gastrin-17 or by inhibition of gastric acid secretion with omeprazole. The investigations demonstrate that there are several types of glycoconjugates in the intercellular spaces of the epithelium with heaviest accumulation in the stratum superficiale. Perfusion with pepsin/HCl reduces, not only the staining intensity of some of these glycoconjugates, but also the transmural electrical resistance. In these studies of acute damage sucrose octasulfate provided some protection. Myotomy of the gastroesophageal sphincter leads to a decrease in lower esophageal sphincter pressure, chronic reflux esophagitis with inflammation, basal cell hyperplasia and erosions, resembling reflux esophagitis in man. The cell turnover time in the epithelium of normal rat esophagus averages 10.4 days; hypergastrinemia shortens this by about 10%; in these rats the esophageal epithelium becomes almost 20% thinner than in the controls