title: Short-time rabbit model of endotoxin-induced hypercoagulability.
abstract: We describe a short-time endotoxin-induced rabbit model of hypercoagulability for the study of the coagulation cascade and the therapeutic effects of coagulation inhibitors. Cardiorespiratory function was maintained 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 prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen concentration, platelet count, fibrin monomers, D-dimers, antithrombin III and factor XIII activities, thrombelastography, and platelet aggregometry were measured during a 4-h period after sequential double endotoxin administration (80 and 40 micrograms/kg of body weight, intravenously). 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 endotoxin-treated animals but was mainly unaltered in controls (P < 0.05). Tissue specimens of the lungs, liver, brain, and kidneys were examined. Endotoxin-induced, disseminated fibrin deposition was found in the lungs and liver (P < 0.01). We conclude that this short-time model of hypercoagulability in rabbits reliably induced disseminated intravascular coagulation. Tracheostomy and mechanical ventilation provided a reproducible model in which the differences between the controls and the endotoxin-treated animals were exclusively due to administration of endotoxin and not to unforeseen complications of the respiratory system. This model allows the study of therapeutic effects of coagulation inhibitors on endotoxin-induced changes.
authors.affiliation: Institute of Anesthesiology, University Hospital, Essen, Germany.
authors.forename: R U
authors.initials: RU
authors.lastname: Scherer
authors.forename: R M
authors.initials: RM
authors.lastname: Giebler
authors.forename: U
authors.initials: U
authors.lastname: Schmidt
authors.forename: D
authors.initials: D
authors.lastname: Paar
authors.forename: T
authors.initials: T
authors.lastname: Wüst
authors.forename: P
authors.initials: P
authors.lastname: Spangenberg
authors.forename: K
authors.initials: K
authors.lastname: Militzer
authors.forename: H
authors.initials: H
authors.lastname: Hirche
authors.forename: W J
authors.initials: WJ
authors.lastname: Kox
mesh_terms: D000818:Animals; D001777:Blood Coagulation; D001779:Blood Coagulation Factors / Q000032:analysis; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000473:pathology; D004731:Endotoxins / Q000633:toxicity*; D005337:Fibrin / Q000032:analysis; D006439:Hemodynamics; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D011817:Rabbits
chemical_list: D001779:Blood Coagulation Factors; D004731:Endotoxins; D005337:Fibrin