Extracorporeal circulation: in vivo and in vitro analysis of complement activation by heparin-bonded surfaces.

Complement activation was analyzed during extracorporeal CO2 removal to compare heparin-coated with standard surfaces where systemic heparinization was required. In vivo studies were performed in adult sheep for up to 5 days under standardized conditions using a capillary membrane oxygenator. Applying assays for hemolytic complement function (CH50, APH50) and C3-derived split products, we found that complement activation was markedly reduced in sheep connected to an extracorporeal circuit where heparin was covalently bound by end-point attachment. In addition, incubation of human serum in a miniaturized circulation system revealed less complement activation by heparin-bonded surfaces, as evaluated by enzyme-linked immunosorbent assays for C3a and the activation-specific protein-protein complexes, C1rsC1 inhibitor (classical pathway) and C3b(Bb)P (alternative pathway). Our results provide further evidence that biocompatibility can be improved by end-point attachment of heparin to the surfaces of the extracorporeal circuit.