BENEFICIAL-EFFECTS OF C1 ESTERASE INHIBITOR IN MURINE TRAUMATIC SHOCK

Activation of the complement system is an integral part of the initiat ion and maintenance of the inflammatory process such as that occurring in traumatic shock, and is considered responsible for much of the tra uma-induced microvascular injury. 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 subjecte d to Noble-Collip drum trauma developed a shock state characterized by marked hypotension and a 83.3% mortality rate with a mean survival ti me of 157.5 +/- 26 min. Accompanying these effects were significant en dothelial dysfunction and elevated intestinal myeloperoxidase activity . Treatment with C1 INH 15 mg/kg administered intravenously 10 min pos t-trauma, increased survival rate to 66.7% (p < .05), and prolonged su rvival time to 248 +/- 27 min (p < .05). C1 INH significantly preserve d the endothelium-dependent relaxation to acetylcholine and attenuated the increases in myeloperoxidase activity in C1 INH-treated rats comp ared with untreated trauma rats (p < .05). Our results suggest that co mplement activation plays an important role in tissue injury associate d with trauma, and that its inhibition at an early step in the complem ent cascade through a C1 esterase inhibitor is beneficial in rats expe riencing traumatic shock. The mechanisms of the protective effect of C 1 INH involves preservation of vascular endothelial function and dimin ished neutrophil accumulation leading to reduced neutrophil-mediated t issue injury.