Beneficial effect of glycoprotein IIb/IIIa inhibitor (AZ-1) on endothelium in Escherichia coli endotoxin-induced shock.
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.
Pu
Q
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Department of Pharmacology, Lille University Hospital, 59037 Lille Cedex, France.
Wiel
E
E
Corseaux
D
D
Bordet
R
R
Azrin
M A
MA
Ezekowitz
M D
MD
Lund
N
N
Jude
B
B
Vallet
B
B
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
D000911:Antibodies, Monoclonal; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014665:Vasodilator Agents