EFFECT OF BN-50727 ON PATHOLOGICAL FINDINGS AND TISSUE PLATELET-ACTIVATING-FACTOR LEVELS DURING ILEAL ISCHEMIA IN NEWBORN PIGLETS

The role of platelet activating factor (PAF), a potent ulcerogen media tor in the digestive tract, is thought to be important in the genesis of necrotizing enterocolitis, The aim of this study was to evaluate th e role of PAF in the perpetuation and aggravation of gastrointestinal damage resulting from limited ischemia in the 2-day-old piglet using a natural PAF antagonist (BN 50727). Animals were separated into six gr oups: U-4, controls; S, sham operated animals undergoing laparotomy; I -4 and I-9, ligation of the mesenteric vessels in the last ileal loop; IT4 and IT9, same procedure together with treatment with BN 50727 (50 mg/kg) orally before and after surgery and intraperitoneally during s urgery. Animals were killed at day 4 in groups U-4, S, I-4 and IT4 and at day 9 in groups I-g and ITg, with histological studies and mediato r measurements taken. Macroscopic and histological lesions of intestin al wall in groups I-4, I-9, IT4 and IT9 were similar to those of human neonatal necrotizing enterocolitis and did not vary according to the absence or the presence of BN 50727 treatment (P = .7, I-4 v IT4 and P = .9, I-9 v IT9). Peritoneal bands were significantly reduced in trea ted groups IT4 and IT9 as compared with untreated ones I-4 and I-9 (P = .003). Mucosal PAF levels in the terminal ileum were higher in group 14 than in groups U-4 or I-g. In the upper loop, mucosal PAF levels w ere comparable in all groups. An increase in stool PAF levels was obse rved only in group I-g (26.4 ng/g v 4.7 ng/g, I-9 v U-4 + S, P < .05), whereas values comparable to those observed in controls were detected in other groups (I-4, 7.2 ng/g; IT4, 4.5 ng/g; IT9, 6.8 ng/g). Tumor necrosis factor alpha (TNF alpha) measurements did not exhibit any dif ference between groups. Using a PAF antagonist, the role of PAF in the aggravation of intestinal damage after ischemia was not remarkable be cause treatment did not induce any modifications of parietal intestina l lesions. PAF antagonists appeared to reduce significantly the local peritoneal consequences of local inflammation. Copyright (C) 1996 by W .B. Saunders Company.