Complement inhibition with soluble complement receptor type 1 in cardiopulmonary bypass

Although complement activation during cardiopulmonary bypass (CPB) is well documented, its pathogenic role in postperfusion organ injury is unproven. In this study, soluble human complement receptor type 1 (sCR1), a potent inhibitor of complement activation, was used to determine the contribution of complement activation to pulmonary injury in a porcine model of CPB. In vitro experiments demonstrated that sCR1 inhibits both classic and alternative complement pathways in the pig. Seven control piglets and 6 piglets treated with sCR1 (12 mg/kg intravenously) underwent 2 hours of hypothermic (28 °C) CPB followed by 2 hours of observation. In control piglets, total hemolytic complement activity and functional activities of C3 and C5 declined to 61.3%, 67.8%, and 61.4% of prebypass values, respectively, after 2 hours of CPB. Plasma from animals treated with sCR1 had virtually no hemolytic activity (total hemolytic complement activity < 5% of baseline), demonstrating effective complement inhibition. Similar degrees of neutropenia developed in the two groups during CPB, and there was no difference in post-CPB lung tissue myeloperoxidase level. Two hours after CPB, pulmonary vascular resistance increased 338% in control piglets but only 147% in piglets pretreated with sCR1 (p < 0.05); the alveolar-arterial gradient was not significantly different between controls (331 ± 52 mm Hg) and piglets receiving sCR1 (290 ± 85 mm Hg), Histologic examination revealed similar degrees of pulmonary edema in both groups. These data constitute direct evidence that complement activation plays a pathogenic role in lung injury after CPB. Although pretreatment with sCR1 ameliorated lung injury after CPB, resulting in decreased pulmonary hypertension, complement inhibition did not improve post-CPB oxygenation and had no significant effect on leukocyte kinetics or lung histology. Thus, complement participates in the pathogenesis of lung injury after CPB, but is not responsible for all of the pulmonary damage.