There are considerable experimental data concerning the role of mucosal blood flow in protecting the gastric mucosa against injury. In contrast, there is a marked lack of analogous data concerning the role of mucosal blood flow in duodenal mucosal defense and injury. The intent of this proposal is to help fill this gap in our knowledge. The applicant's laboratory recently has validated the hydrogen gas clearance technique to measure gastric and duodenal mucosal blood flow. In addition, studies have begun concerning the use of iodo (14C) antipyrine autoradiography to detect very localized blood flows in each layer of the duodenum. These techniuqes will be applied to well-established models of duodenal ulcer in the rat-, cysteamine-, mepirazole- and secretagogue-induced. Blood flow results at different times after administration of ulcerogenic agents will be compared with gross and histologic mucosal injury to ascertain whether blood flow changes precede the earliest evidence of mucosal damage, and, hence, may be pathogenetic. Agents known to protect against or aggravate such ulcers will be studied for their effect or duodenal mucosal blood flow. In particular, the role of prostaglandins, both exogenous and endogenous, will be studied in this regard. Duodenal mucosal bicarbonate secretion also may be an important defensive factor. Therefore, the question of the relation of a duodenal mucosal blood flow to bicarbonate secretion will be addressed. Since gastric hydrochloric acid is an important noxious factor in duodenal mucosal injury, the effect on duodenal mucosal blood flow or perfusion of the duodenal lumen with hydrochloric acid will be investigated. Motility has been implicated as a factor in gastric musocal injury by some workers. Therefore, studies of the effectg of duodenal motility on duodenal mucosal blood flow will be undertaken. The question of the effect of solids, both nutrient and non-nutrient, on duodenal motility and mucosal blood flow also will be investigated.
