{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T22:35:10Z","timestamp":1771626910315,"version":"3.50.1"},"reference-count":22,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:p>BACKGROUND: In contrast with earlier reports that neutrophils play a primary part in non-steroidal anti-inflammatory drug (NSAID) injury to the stomach, recent evidence suggests only a secondary role for these cells. AIM: To examine whether early microscopic changes induced by indomethacin in the gastric corpus of fasted rats and the antrum of fasted-refed rats involve neutrophil infiltration. METHODS: Oral indomethacin 30 mg\/kg or vehicle was given to six groups of fasted rats that were killed five, 15, and 30 minutes after dosing. Subcutaneous indomethacin 30 mg\/kg was also given to six groups of fasted-refed rats that were killed one, two, and four hours later. Haematoxylin and eosin and reticulin stained sections were examined to identify mucosal architectural changes. The gastric mucosa was also examined immunohistochemically for actin, fibrin, and neutrophils. RESULTS: In both the corpus and antrum, indomethacin caused an early phase of mucosal injury that occurred prior to mucosal neutrophil infiltration. Within the superficial corpus mucosa, this phase preceded coagulative necrosis and included surface epithelial expulsion, mucosal contraction with capillary aggregation and distortion, intravascular vascular fibrin deposition, and capillary congestion. The antrum showed similar early changes except that full thickness mucosal coagulative necrosis was a predominant early finding. CONCLUSIONS: In two experimental models of NSAID gastric ulceration the mucosa undergoes early contraction, vascular fibrin deposition, and necrosis prior to neutrophil infiltration. These findings support a primary, neutrophil independent, ischaemic pathogenesis for NSAID gastric ulceration.<\/jats:p>","DOI":"10.1136\/gut.39.3.363","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"363-368","source":"Crossref","is-referenced-by-count":24,"title":["Gastric mucosal contraction and vascular injury induced by indomethacin precede neutrophil infiltration in the rat."],"prefix":"10.1136","volume":"39","author":[{"given":"A","family":"Anthony","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Sim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A P","family":"Dhillon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R E","family":"Pounder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A J","family":"Wakefield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1996,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1001\/archinte.1987.00370120029008","article-title":"Non-steroidal anti-inflammatory drug gastropathy: Recognition and response","volume":"147","author":"Roth, S.H.; Bennett, R.E.","year":"1987","unstructured":"Roth SH, Bennett RE. Non-steroidal anti-inflammatory drug gastropathy: Recognition and response. Arch Intern Med 1987; 147: 2093-100.","journal-title":"Arch Intern Med"},{"issue":"1","key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000171523","article-title":"Non-steroidal anti-inflammatory drugs: How do they damage gastroduodenal mucosa?","volume":"13","author":"Scarpignato, C.","year":"1995","unstructured":"Scarpignato C. Non-steroidal anti-inflammatory drugs: How do they damage gastroduodenal mucosa? Dig Dis 1995; 13 (suppl 1): 9-39.","journal-title":"Dig Dis"},{"key":"ref_3","first-page":"462","article-title":"Gastric ulceration induced by non-steroidal anti-inflammatory drugs is a neutrophil dependent process","volume":"259","author":"Wallace, J.L.; Keenan, C.M.; Neil Granger, D.","year":"1990","unstructured":"Wallace JL, Keenan CM, Neil Granger D. Gastric ulceration induced by non-steroidal anti-inflammatory drugs is a neutrophil dependent process. Am Jf Physiol 1990; 259: G462-7.","journal-title":"Am Jf Physiol"},{"key":"ref_4","first-page":"878","article-title":"A monoclonal antibody against","volume-title":"the CD1 8 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. Gastroenterology 1991","volume":"100","author":"Wallace, J.L.; Arfors, K.E.; Webb McKnight, G.","unstructured":"Wallace JL, Arfors KE, Webb McKnight G. A monoclonal antibody against the CD1 8 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. Gastroenterology 1991; 100: 878-83."},{"key":"ref_5","first-page":"920","article-title":"Aspirin-induced gastric mucosal injury is a neutrophil-dependent process in rats","volume":"263","author":"Lee, M.; Aldred, K.; Lee, E.; Feldman, M.","year":"1992","unstructured":"Lee M, Aldred K, Lee E, Feldman M. Aspirin-induced gastric mucosal injury is a neutrophil-dependent process in rats. Am _J Physiol 1992; 263: G920-6.","journal-title":"Am _J Physiol"},{"key":"ref_6","first-page":"993","article-title":"Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury","volume":"265","author":"Wallace, J.L.; McKnight, W.; Miyasaka, M.; Tamatani, T.; Paulson, J.; Anderson, D.C.","year":"1993","unstructured":"Wallace JL, McKnight W, Miyasaka M, Tamatani T, Paulson J, Anderson DC, et al. Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury. Am _J Physiol 1993; 265: G993-8.","journal-title":"Am _J Physiol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3109\/00365529209095973","article-title":"Non-steroidal anti-inflammatory drug gastropathy and cytoprotection: Pathogenesis and mechanisms re-examined","volume":"192","author":"Wallace, J.L.","year":"1992","unstructured":"Wallace JL. Non-steroidal anti-inflammatory drug gastropathy and cytoprotection: Pathogenesis and mechanisms re-examined. 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