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

The use of non-steroidal antiinflammatory drugs (NSAIDs) to treat chro nic inflammatory conditions is often limited by drug-induced ulceratio n of the GI tract. Effective protection of this mucosa is highly desir able. A model of indomethacin (IND)-induced ulceration of the antrum i n starved-refed rats was used to investigate the sequence of events le ading 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 IN D. Mucosal death was coagulative and spread from the luminal surface. Neutrophils (PMNs) arrived after mucosal necrosis had appeared, and fo rmed a band beneath the dead tissue but did not enter it. The results suggest that extra vascular PMNs do not contribute to mucosal damage i n this model.