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 mediator in the digestive tract, is thought to be important in the genesis of necrotizing enterocolitis. The aim of this study was to evaluate the 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 groups: U4, controls; S, sham operated animals undergoing laparotomy; I4 and I9, 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 surgery. Animals were killed at day 4 in groups U4, S, I4 and IT4 and at day 9 in groups I9 and IT9, with histological studies and mediator measurements taken. Macroscopic and histological lesions of intestinal wall in groups I4, I9, 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, I4 v IT4 and P = .9, I9 v IT9). Peritoneal bands were significantly reduced in treated groups IT4 and IT9 as compared with untreated ones I4 and I9 (P = .003). Mucosal PAF levels in the terminal ileum were higher in group I4 than in groups U4 or I9. In the upper loop, mucosal PAF levels were comparable in all groups. An increase in stool PAF levels was observed only in group I9 (26.4 ng/g v 4.7 ng/g, I9 v U4 + S, P < .05), whereas values comparable to those observed in controls were detected in other groups (I4, 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 difference between groups. Using a PAF antagonist, the role of PAF in the aggravation of intestinal damage after ischemia was not remarkable because treatment did not induce any modifications of parietal intestinal lesions. PAF antagonists appeared to reduce significantly the local peritoneal consequences of local inflammation.
de Boissieu
D
D
Hôpital Saint Vincent de Paul, Paris, France.
Canarelli
J P
JP
Cordonnier
C
C
Richard
S
S
Léké
A
A
Tarrade
T
T
Postel
J P
JP
Dupont
C
C
D000818:Animals; D000831:Animals, Newborn; D001381:Azepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology / Q000473:pathology; D006801:Humans; D007082:Ileum / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D007231:Infant, Newborn; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D013552:Swine; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001381:Azepines; D010972:Platelet Activating Factor; D058924:Thienopyridines; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C067429:Setipafant