SHORT-TIME RABBIT MODEL OF ENDOTOXIN-INDUCED HYPERCOAGULABILITY

We describe a short-time, endotoxin-induced rabbit model of hypercoagu lability for the study of the coagulation cascade and the therapeutic effects of coagulation inhibitors. Cardiorespiratory function was main tained in rabbits under general anesthesia and standardized mechanical ventilation (tidal volume, 6 ml/kg; 60 breaths/min) via tracheostomy and low-dose inotropic support. Coagulation parameters such as prothro mbin time, activated partial thromboplastin time, thrombin time, fibri nogen concentration, platelet count, fibrin monomers, D-dimers, antith rombin III and factor XIII activities, thrombelastography, and platele t aggregometry were measured during a 4-h period after sequential doub le endotoxin administration (80 and 40 mu g/kg of body weight, intrave nously). Mean arterial pressure and arterial and central venous blood gas tensions were monitored. Global clotting, activation parameters of coagulation, and leukocyte count deteriorated significantly in the en dotoxin-treated animals but was mainly unaltered in controls (P < 0.05 ). Tissue specimens of the lungs, liver, brain, and kidneys were exami ned, Endotoxin-induced, disseminated fibrin deposition was found in th e lungs and liver (P < 0.01). We conclude that this short-time model o f hypercoagulability in rabbits reliably induced disseminated intravas cular coagulation. Tracheostomy and mechanical ventilation provided a reproducible model in which the differences between the controls and t he endotoxin-treated animals were exclusively due to administration of endotoxin and not to unforeseen complications of the respiratory syst em, This model allows the study of therapeutic effects of coagulation inhibitors on endotoxin-induced changes.