Combined antithrombin III and C1-esterase inhibitor treatment decreases intravascular fibrin deposition and attenuates cardiorespiratory impairment in rabbits exposed to Escherichia coli endotoxin

Objective: To assess the effect of a combined antithrombin III and C1-esterase inhibitor treatment on intravascular organ fibrin deposition and cardiorespiratory changes following intravenous Escherichia coli endotoxin (lipopolysaccharide [LPS] 80 mu g/kg iv) exposure. Design: Prospective, randomized trial. Setting: Research laboratory of a university medical center. Subjects: Anesthetized, instrumented and mechanically ventilated rabbits ([Chbb:CH); n = 40), Interventions: Endotoxin was given to 30 animals. Ten animals received no inhibitor (endotoxin control group). The other animals were either treated by high-dose (300 units/kg; n = 10) or low-dose (100 units/kg; n = 10)combined antithrombin III and C1-esterase inhibitor administration, Ten rabbits (time control group) were given placebo (sodium chloride 0.9%), Cardiorespiratory variables were assessed at baseline, 120 mins, and 240 mins after endotoxin or placebo administration. Four hours after endotoxin injection, liver, lung, and kidney tissue samples were examined for intravascular fibrin deposition by light microscopy. Measurements and Main Results: Inhibitor treatment significantly decreased clot formation in lungs and livers without, however, demonstrating a clear dose dependent effect. Combined antithrombin III/C1-esterase treatment attenuated the decrease of mean arterial pressure and cardiac output observed following endotoxin injection. Blood pressure improvement was significantly dependent on dosage administered. Conclusion: Combination of antithrombin III and C1-esterase inhibitor treatment during early endotoxin shock decreased organ fibrin deposition and improved cardiovascular stability.