HISTOLOGICAL EVIDENCE THAT VASCULAR DAMAGE AND MUCOSAL ULCERATION CAUSED BY INDOMETHACIN PRECEDE NEUTROPHIL INFILTRATION IN THE RAT GASTRIC ANTRUM

The use of non-steroidal antiinflammatory drugs (NSAIDs) to treat chronic inflammatory conditions is often limited by drug-induced ulceration of the GI tract. Effective protection of this mucosa is highly desirable. A model of indomethacin (IND)-induced ulceration of the antrum in starved-refed rats was used to investigate the sequence of events leading to mucosal damage, by examining tissues microscopically. Venous congestion was seen to precede mucosal damage in starved rats, and to occur even in non-starved rats that did not ulcerate in response to IND. Mucosal death was coagulative and spread from the luminal surface. Neutrophils (PMNs) arrived after mucosal necrosis had appeared, and formed a band beneath the dead tissue but did not enter it. The results suggest that extra vascular PMNs do not contribute to mucosal damage in this model.