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 nonlet hal septic rabbit model. Design: Randomized, controlled, interventional trial. Setting: University animal laboratory. Subjects: A total of 30 male New Zealand White rabbits, randomly assigned t o one of two groups. Interventions: Male New Zealand White rabbits were randomly divided into co ntrol or lipopolysaccharide (LPS) (0.5 mg/kg iv bolus Escherichia coil endo toxin)-treated groups. Metabolic acidosis and coagulation activation confir med the presence of septic shock. The abdominal aorta was removed at 24 hrs (day 1), day 5, or day 21 after LPS injection. Immunohistochemical stainin g for an endothelial cell marker (PECAM-1/CD31) was performed to assess end othelial injury. Endothelium-dependent vascular relaxation was analyzed by in vitro vascular reactivity studies. Responses to acetylcholine, to calciu m ionophore (A-23187), and to sodium nitroprusside were studied. In additio n, arterial blood samples were collected on day 1, day 5, and day 21 for me asurement 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 disap peared on day 21. LPS injection also caused a significantly reduced relaxat ion response to acetylcholine (44.9% +/-9.9% vs. 76.5% +/-5.4% for the cont rol group; p < .005), which was restored on day 21. In contrast, vascular r elaxation in response to A-23187 and sodium nitroprusside was not altered. A significant decrease in the platelet count was observed on day 1, associa ted with a decrease in factors II and V. On day 5, platelet count and facto rs II and V were corrected in conjunction with an elevated monocyte tissue factor activity in LPS-injected rabbits. On day 21, coagulation abnormaliti es were corrected. Conclusions: A single endotoxin injection in the rabbit was responsible for prolonged aortic endothelial cell dysfunction, as well as a prolonged proc oagulant state. The latter is a potential trigger for disseminated intravas cular coagulation. Importantly, these features are associated with normaliz ation of conventional biological evidence of septic shock.