DEVELOPMENT, EVOLUTION AND HEALING OF EXPERIMENTAL GASTRIC-ULCERS - AN OVERVIEW

Background and aims: In previous studies we have analyzed the time seq uence, histologic, cellular, ultrastructural and molecular aspects of the formation and evolution of experimental, acetic acid-induced gastr ic ulcerations. Using these studies and pertinent work by other invest igators, we reviewed the development, evolution and healing of experim ental gastric ulcers. Sequence of ulcer formation: Following exposure of the gastric mucosa to acetic acid, the earliest morphologic changes occur after 1-5 min and consist of necrosis of endothelial cells in l arge submucosal vessels and collecting venules, leading to thrombi and thus microvascular stasis, ischemia and mucosal necrosis. After 3-24 h, necrotic masses become detached. By 24-48 h, necrotic changes have penetrated the submucosa. By 72 h, most ulcers have undergone a transi tion into a chronic stage, characterized histologically by the presenc e of granulation tissue at the bottom, and the appearance of a transit ional healing zone at the margin. By 5 days, gastric glands in the tra nsitional zone at the ulcer margin display dilation and marked cell pr oliferation, which provides cells for migration and re-epithelializati on and reconstruction of the mucosal glandular structures. Granulation tissue, which develops at the ulcer base and consists of proliferatin g microvessels, macrophages and fibroblasts, grows intensively, supply ing connective tissue cells and matrix for restoration of the lamina p ropria and microvessels for reconstruction of the microvascular networ k within the mucosal scar. Conclusions: The final outcome of the heali ng process reflects a dynamic interaction between the epithelial compo nent from the healing zone at the ulcer margin and the connective tiss ue component (including microvessels) originating from the granulation tissue.