Ultrastructural study of experimental duodenal ulcer in a new animal model

Various animal models have often been utilized as the basis of studies of the pathophysiology of peptic ulcer disease, however the ultrastructural changes in the evolution of duodenal ulcers produced in experimental animals have not been well elucidated. Utilizing a surgical method developed for the study of gastric ulcers we have established an experimental duodenal ulcer production technique in the rat which is highly reproducible and readily standardized. In the following time sequence study of experimental duodenal ulcers we present the ultrastructural features of ulcer induction and evolution.Duodenal ulcers were produced in 150-200 gram male Sprague Dawley rats by application of 50% acetic acid for 30 seconds through a 3 mm polyethylene tube to the serosa 1.0-1.5 cm distal to the pyloric sphincter. Routine transmission and scanning electron microscopy were performed on duodenal specimens at specific time points subsequent to surgical ulcer generation. Thin sections were stained with uranyl acetate and lead citrate and examined with a Phillip's EM 300 transmission electron microscope. For SEM, specimens were post-fixed in 2% osmium for two days, coated with gold/palladium and examined with JEOL JSM-6100 scanning electron microscope (JEOL, Inc., Peabody, MA).

Direct measurement of duodenal acid-pepsin exposure at site of ulceration in rats

A new technique for the preparation of a chronic duodenal fistula in the rat is described. The effect of cysteamine and propionitrile on the acidity of duodenal contents was studied, and the degree of acidity correlated with the respective duodenal ulcerogenicity of these two compounds. After subcutaneous administration of cysteamine, reduced duodenal acid was seen for 2-4 h, followed by large increases continuing up to 12 h and declining thereafter. Oral cysteamine administration produced acid increases of rapid onset and shorter duration, accompanied by increased pepsin activity. The weak duodenal ulcerogen propionitrile did not affect duodenal acidity. Cimetidine markedly reduced the duodenal acidification induced by cysteamine, whereas the dopamine agonist bromocriptine did not affect acid delivery to the duodenum but reduced the pepsin activity in the duodenal contents by 50%. The duodenal fistula rat provides a new model system for studies on the pathogenesis of experimental duodenal ulcer.