A single endotoxin injection in the rabbit causes prolonged blood vessel dysfunction and a procoagulant state

Objectives: To determine the duration of vascular blood vessel dysfunction and coagulation abnormalities after administration of endotoxin in a nonlethal septic rabbit model. Design: Randomized, controlled, interventional trial. Setting: University animal laboratory. Subjects: A total of 30 male New Zealand White rabbits, randomly assigned to one of two groups. Interventions: Male New Zealand White rabbits were randomly divided into control or lipopolysaccharide (LPS) (0.5 mg/kg iv bolus Escherichia coli endotoxin)-treated groups. Metabolic acidosis and coagulation activation confirmed the presence of septic shock. The abdominal aorta was removed at 24 hrs (day 1), day 5, or day 21 after LPS injection. Immunohistochemical staining for an endothelial cell marker (PECAM-1/CD31) was performed to assess endothelial injury. Endothelium-dependent vascular relaxation was analyzed by in vitro vascular reactivity studies. Responses to acetylcholine, to calcium ionophore (A-23187), and to sodium nitroprusside were studied. In addition, arterial blood samples were collected on day 1, day 5, and day 21 for measurement of clotting factors and tissue factor activity. Measurements and Main Results: LPS injection resulted in endothelial injury, with loss of similar to 25% of the endothelial area on day 5, which disappeared on day 21. LPS injection also caused a significantly reduced relaxation response to acetylcholine (44.9% +/-9.9% vs. 76.5% +/-5.4% for the control group; p < .005), which was restored on day 21. In contrast, vascular relaxation in response to A-23187 and sodium nitroprusside was not altered. A significant decrease in the platelet count was observed on day 1, associated with a decrease in factors II and V. On day 5, platelet count and factors II and V were corrected in conjunction with an elevated monocyte tissue factor activity in LPS-injected rabbits. On day 21, coagulation abnormalities were corrected. Conclusions: A single endotoxin injection in the rabbit was responsible for prolonged aortic endothelial cell dysfunction, as well as a prolonged procoagulant state. The latter is a potential trigger for disseminated intravascular coagulation. Importantly, these features are associated with normalization of conventional biological evidence of septic shock.