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.
Kirschfink
M
M
Institute of Immunology, University of Heidelberg, Federal Republic of Germany.
Kovacs
B
B
Mottaghy
K
K
D000818:Animals; D001672:Biocompatible Materials; D002245:Carbon Dioxide / Q000097:blood; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D003170:Complement Pathway, Alternative; D004797:Enzyme-Linked Immunosorbent Assay; D005112:Extracorporeal Circulation / Q000295:instrumentation*; D006493:Heparin / Q000494:pharmacology*; D012756:Sheep
D001672:Biocompatible Materials; D002245:Carbon Dioxide; D015926:Complement C3a; D003179:Complement C3b; D006493:Heparin