Experimental necrotizing enterocolitis: the role of polymorphonuclear neutrophils.
Polymorphonuclear neutrophils (PMNs) play an important role in inflammation. Activated PMNs adhere to the vascular wall and release reactive oxygen radicals and enzymes, producing vascular injury. In the present study, we investigated whether PMNs play an important role in the pathogenesis of experimental necrotizing enterocolitis (NEC). NEC was induced in rats using platelet activating factor (PAF, 1 microgram/kg) and bacterial endotoxin (LPS, 1 mg/kg) intravenously. Neutropenia was accomplished by parenteral injection of Vinblastine (VB, 0.75 mg/kg) 4 days before the experiment to deplete the total white blood cell (WBC) and neutrophil counts. The animals were divided into 4 groups: (1) 1 microgram/kg PAF; (2) 1 mg/kg LPS; (3) 1 microgram/kg PAF + 1 mg/kg LPS; and (4) PMN depleted, 1 microgram/kg PAF + 1 mg/kg LPS. Combined administration of PAF and LPS produced prolonged hypotension (blood pressure 53.5 +/- 13.8 mm Hg at 2 hours), leukopenia (4,062 +/- 497.4), hemoconcentration (hematocrit 44.5% +/- 1.1%), reduced intestinal perfusion (74% +/- 13.3%), and segmental bowel necrosis. However, in VB-treated animals combined PAF + LPS induced only mild hypotension (84.3 +/- 9.2 mm Hg at 2 hours) and no hemoconcentration. In these animals the intestinal perfusion was normal, no bowel necrosis was observed, and the intestinal myeloperoxidase activity (.0034 +/- .0017 U/g tissue) was significantly lower than that of the nondepleted group (.0075 +/- .0012 U/g tissue). We conclude that the presence of neutrophils and/or neutrophil products play a major role in the pathogenesis of NEC.
Children's Memorial Hospital, Chicago, IL.
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C
Musemeche
M
M
Caplan
W
W
Hsueh
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X
Sun
A
A
Kelly
D000818:Animals; D001794:Blood Pressure; D004761:Enterocolitis, Pseudomembranous / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D006400:Hematocrit; D007422:Intestines / Q000098:blood supply; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow
D008070:Lipopolysaccharides; D010972:Platelet Activating Factor