title: Beneficial effect of glycoprotein IIb/IIIa inhibitor (AZ-1) on endothelium in Escherichia coli endotoxin-induced shock.
abstract: OBJECTIVE
  To investigate the effects of AZ-1, a murine monoclonal antiglycoprotein-IIb/IIIa antibody, on endothelium and on hemostasis in a rabbit endotoxic shock model.
  
  
  METHODS
  Prospective laboratory study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Thirty-five male New-Zealand rabbits.
  
  
  METHODS
  In vitro vascular reactivity, endothelium CD31-PECAM1 immunohistochemistry, plasma coagulation factors, and monocyte tissue factor determination were performed 1 day and/or 5 days after onset of endotoxic shock (0.5 mg/kg, intravenous bolus,Escherichia coli lipopolysaccharide) with or without treatment by AZ-1 (0.5 mg/kg intravenously) given 1 hr after lipopolysaccharide injection.
  
  
  RESULTS
  Metabolic acidosis and coagulation activation confirmed the presence of shock. AZ-1 treatment improved endothelial-dependent relaxation at 1 day (maximal effect = 87.2 +/- 4.0% vs. 60.9 +/- 5.2% in the nontreated group, p <.05) and at 5 days (maximal effect = 84.5 +/- 3.5% vs. 56.6 +/- 8.2% in the nontreated group, p <.05). Endotoxin-induced endothelial injury was decreased significantly by AZ-1 at 1 day (6.4 +/- 1.9% vs. 10.3 +/- 0.8% in the nontreated group, p <.05) and at 5 days (6.3 +/- 2.0% vs. 20.2 +/- 1.2% in the nontreated group, p <.05). Monocyte tissue factor expression was significantly reduced at 5 days.
  
  
  CONCLUSIONS
  These data indicate that potent inhibition of platelet function via antiglycoprotein-IIb/IIIa receptor blockade can inhibit coagulation activation and protect against endothelial dysfunction and histologic injury in endotoxin-induced shock.
authors.affiliation: Department of Pharmacology, Lille University Hospital, 59037 Lille Cedex, France.
authors.forename: Q
authors.initials: Q
authors.lastname: Pu
authors.forename: E
authors.initials: E
authors.lastname: Wiel
authors.forename: D
authors.initials: D
authors.lastname: Corseaux
authors.forename: R
authors.initials: R
authors.lastname: Bordet
authors.forename: M A
authors.initials: MA
authors.lastname: Azrin
authors.forename: M D
authors.initials: MD
authors.lastname: Ezekowitz
authors.forename: N
authors.initials: N
authors.lastname: Lund
authors.forename: B
authors.initials: B
authors.lastname: Jude
authors.forename: B
authors.initials: B
authors.lastname: Vallet
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D004926:Escherichia coli; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011817:Rabbits; D012044:Regression Analysis; D012772:Shock, Septic / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014665:Vasodilator Agents