Enhanced Coagulatory and Inflammatory Response Associated with Complement-1 Inhibitor (C1-INH) Administration in a Pig Lung Transplant Survival Model

Complement inhibition has been shown to be beneficial in the treatment of ischemia-reperfusion injury. The effects of complement-1 inhibitor (C1-INH) were evaluated in a pig lung transplant model. Left single lung transplantation was performed in animals randomized to either a control group or treated with 200 U/kg of C1-INH. Allograft functions were assessed at 1 hour and 72 hours after reperfusion. All control animals survived to sacrifice on postoperative day 3. Two out of 4 animals in the treatment arm, however, developed graft failure and experiments were terminated early. Autopsy showed major pulmonary artery thrombus in one and bronchial casts in both failed treatment animals. The C1-INH group exhibited enhanced coagulation activation as well as more severe acute lung injury and inflammation. Early complement activation was weaker in the control group. The safety of C1-INH needs to be reconsidered as a potential therapy for ischemia-reperfusion induced injury in lung transplantation.M.Sc