C1 esterase inhibitor reduces lower extremity ischemia/reperfusion injury and associated lung damage

C1 酯酶抑制剂可减轻下肢缺血/再灌注损伤及相关肺损伤

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作者:Claudia Duehrkop, Yara Banz, Rolf Spirig, Sylvia Miescher, Marc W Nolte, Martin Spycher, Richard A G Smith, Steven H Sacks, Robert Rieben

Background

Ischemia/reperfusion injury of lower extremities and associated lung damage may result from thrombotic occlusion, embolism, trauma, or surgical intervention with prolonged ischemia and subsequent restoration of blood flow. This clinical entity is characterized by high morbidity and mortality. Deprivation of blood supply leads to molecular and structural changes in the affected tissue. Upon reperfusion inflammatory cascades are activated causing tissue injury. We therefore tested preoperative treatment for prevention of reperfusion injury by using C1 esterase inhibitor (C1 INH).

Conclusions

C1 INH reduced edema formation locally in reperfused muscle as well as in lung, and improved muscle viability. C1 INH did not primarily act via inhibition of the complement system, but via the kinin and coagulation cascade. APT070 did not show beneficial effects in this model, despite potent inhibition of complement activation. Taken together, C1 INH might be a promising therapy to reduce peripheral ischemia/reperfusion injury and distant lung damage in complex and prolonged surgical interventions requiring tourniquet application.

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