C1 inhibitor prevents capillary leakage after thermal trauma

Objective:ln burned patients, activation of the complement and clotting systems is suggested to play an important role in the development of the capillary leak syndrome and inflammatory tissue destruction. In an animal model of thermal trauma, the possible protective effect of C1 inhibitor (C1lnh), a major control protein of both the complement and clotting systems, was investigated, Design:Prospective, controlled study. Setting: Animal model. Subjects: Healthy pigs weighing 30 kg, Interventions: Pigs were scalded for 25 sees with 75 degrees C hot water to achieve a 30% total body surface deep partial-thickness burn, The treatment group (n = 8) received C1lnh concentrate at an initial dose of 100 units/kg body weight immediately after thermal trauma, followed by three further applications every 12 hrs, Two control groups included animals that were either scalded (n = 8) or not scalded (n = 7) and treated with lactated Ringer's solution, Measurements: Before and at various time points after trauma blood samples were analyzed for complement activation (APH(50), CH50, SC5b-9, C3), Continuous monitoring of hemodynamic variables was performed and postmortem histologic examination of specimens from lung, heart, liver, kidney, stomach, duodenum, jejunum, ileum, and colon was carried out, Aseptically collected mesenteric lymph nodes were pooled and screened for bacterial translocation, For evaluation of the burn wound, biopsies from defined scalded and not scalded areas were taken daily. As a measure for edema formation, the weight of the animals was recorded every 2 hrs, Results:After C1lnh treatment, which led to a significantly reduced complement activation, the clinical outcome was clearly improved, as indicated by vital signs and as demonstrated by reduced edema formation, Treated animals presented a diminished bacterial translocation, Pathologic alterations were clearly diminished in the burned skin, in shock-related organs, and in the intestines. Conclusion: Application of C1lnh appears to be an effective means to prevent capillary leakage and inflammatory tissue destruction after thermal trauma.