Activation of the complement system is an integral part of the initiation and maintainance of the inflammatory process including traumatic shock, and is considered responsible for much of the microvascular injury occuring in this condition. We investigated the effects of early complement blockade induced by a C1 esterase inhibitor (C1 INH) in a rat model of traumatic shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension and a 83.3% mortality rate with a survival time of 157±26 min. Accompanying these effects are significant endothelial damage and elevated intestinal myeloperoxidase (MPO) activity. Treatment with C1 INH 15 mg/Kg administered intravenously 10 min post trauma, increased survival rate to 66.7% (p<0.05) and prolonged survival time to 247±27 min (p<0.05). C1 INH preserved significantly the endothelium dependent relaxation to ACh and A23187(p<0.01) and attenuated the increases in myeloperoxidase activity to 2.0±0.4 U/100 mg tissue weight in C1 INH treated rats compared to 3.1±0.3 in untreated rats (p<0.05). Our results indicate that complement activation plays an important role in tissue injury associated with trauma, and that its inhibition at an early step in the complement cascade through a C1 esterase inhibitor can be beneficial in traumatic shock in rats. The mechanisms of the protective effect of C1 INH involve preservation of vascular endothelial function and diminished neutrophil accumulation leading to reduced tissue injury.
