Beneficial effect of glycoprotein IIb/IIIa inhibitor (AZ-1) on endotheliumin Escherichia coli endotoxin-induced shock

Objective: To investigate the effects of AZ-1, a murine monoclonal antiglyc oprotein-IIb/IIIa antibody, on endothelium and on hemostasis in a rabbit en dotoxic shock model. Design: Prospective laboratory study. Setting: University laboratory. Subjects: Thirty-five male New-Zealand rabbits. Interventions: In vitro vascular reactivity, endothelium CD31-PECAM1 immuno histochemistry, plasma coagulation factors, and monocyte tissue factor dete rmination were performed 1 day and/or 5 days after onset of endotoxic shock (0.5 mg/kg, intravenous bolus, Escherichia coli lipopolysaccharide) with o r without treatment by AZ-1 (0.5 mg/kg intravenously) given 1 hr after lipo polysaccharide injection. Measurements and Main Results: Metabolic acidosis and coagulation activatio n confirmed the presence of shock. AZ-1 treatment improved endothelial-depe ndent 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-induce d 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 tis sue factor expression was significantly reduced at 5 days. Conclusions: These data indicate that potent inhibition of platelet functio n via antiglycoprotein-IIb/IIIa receptor blockade can inhibit coagulation a ctivation and protect against endothelial dysfunction and histologic injury in endotoxin-induced shock.