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.
Design: Prospective laboratory study.
Setting: University laboratory.
Subjects: Thirty-five male New-Zealand rabbits.
Interventions: 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.
Measurements and main 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.