C-1-ESTERASE INHIBITOR PREVENTS EARLY PULMONARY DYSFUNCTION AFTER LUNG TRANSPLANTATION IN THE DOG

The success of lung transplantation to a large extent depends on effec tive protection of the graft from ischemic injury after reperfusion. A lthough mechanisms have not been clarified, the pathologic findings of ischemic injury after reperfusion are similar to adult respiratory di stress syndrome, a condition in which the blood coagulation contact sy stem is activated. This study evaluates the effect of C-1-esterase inh ibitor (C-1-INH), the main inhibitor of the blood coagulation contact system, on short-term lung function in a dog model of orthotopic lung transplantation. Twelve lung transplantations were performed after 24 h of ischemic time. Dogs were randomly assigned to receive either vehi cle (Control) or C-1-INH. After the lung transplantation in the contro l group, Pa-O2 decreased by 84% and both the AaPO(2) and the Q over do t s/Q over dot t% increased (340 and 530%, respectively, p < 0.01); th ese parameters remained unchanged in the C-1-INH group. The hypoxemia observed in control animals was associated with decreased blood coagul ation contact factors, complement consumption, increased expression of adhesion glycoproteins in leukocytes, and extensive intraalveolar and interstitial neutrophil infiltration. In contrast, C-1-INH administra tion prevented hypoxemia, the decrease in blood coagulation contact fa ctors, the activation of the complement system, the increase in expres sion of leukocyte adhesion molecules, and inflammatory cell infiltrate . This study has demonstrated that in a dog model of lung transplantat ion, the administration of C-1-INH prevents early pulmonary dysfunctio n, and it suggests that activation of blood coagulation contact system and complement are important mechanisms causing ischemic injury after reperfusion.