EXTRACORPOREAL-CIRCULATION - IN-VIVO AND IN-VITRO ANALYSIS OF COMPLEMENT ACTIVATION BY HEPARIN-BONDED SURFACES

Complement activation was analyzed during extracorporeal CO2 removal t o compare heparin-coated with standard surfaces where systemic heparin ization was required. In vivo studies were performed in adult sheep fo r up to 5 days under standardized conditions using a capillary membran e oxygenator. Applying assays for hemolytic complement function (CH50, APH50) and C3-derived split products, we found that complement activa tion was markedly reduced in sheep connected to an extracorporeal circ uit where heparin was covalently bound by end-point attachment. In add ition, incubation of human serum in a miniaturized circulation system revealed less complement activation by heparin-bonded surfaces, as eva luated by enzyme-linked immunosorbent assays for C3a and the activatio n-specific protein-protein complexes, C1 rsC1 Inhibitor (classical pat hway) 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. (C) 1993 Wi ley-Liss, Inc.