Comparative effects of Indomethacin, Prostaglandin E 1, and Ibuprofen on bowel ischemia

Abstract

This study evaluates the effects of Indomethacin (IND), Prostaglandin E1 (PGE1), and Ibuprofen (IBP) in a bowel ischemia model. Laparotomy was performed in 80-gram rats (n = 260). Transient ischemia was induced by a one minute occlusion of the superior mesenteric artery. Animals were placed in five experimental groups: (I) ischemic controls (n = 80), (II) PGE1, 80 micrograms/kg IV (n = 20), (III) IBP, 12.5 mg/kg IV (n = 60), (IV) IND 15 mg/kg IV (n = 80) and (V) PGE1 + IND (n = 20). All medications were given just prior to laparotomy. Animals were evaluated for survival, length of survival and the presence of bowel necrosis and/or perforation at seven days. Survival was 18% in controls and was reduced to 5% by IND (p less than .005). Improved survival was observed with PGE1 (35%), TBP (31%) and PGE1 + IND (35%). IND resulted in early death, while PGE1, IBP, and PGE1 + IND all increased the length of survival (p less than .05). IND-treated rats had a high incidence of bowel perforation (greater than 40%). PGE1 reversed this effect when given concomitantly with IND. IBP had a significantly lower incidence of intestinal necrosis. These data suggest that infants treated with IND who are at risk for NEC should be carefully monitored for evidence of bowel necrosis. PGE1 and IBP may have a cytoprotective role in subjects at risk for bowel ischemia.