Zur Frage der Aktivierung des Gerinnungs- und Komplementsystemes bei Verwendung von oberflächenmodifizierten Biomaterialien

Extracorporeal blood circulation (ECC) for dialysis, cardiopulmonary bypass and extracorporeal membrane oxygenation (ECMO) induces the activation of different humoral and cellular cascade systems. Systemic anticoagulation with heparin inhibits activation of blood coagulation but increases risk of bleeding. Heparin bonded surfaces (HBS) of the biomaterials reduce the activation of coagulation, platelets, complement system and leukocytes according to the type of HBS leading to improved biocompatibility. In this study the biocompatibility of a covalently end-point-attached heparin coating was analyzed in different in-vitro and in-vivo-models considering coagulation and complement systems. Mechanism inhibiting the activation on HBS were examined. An in-vitro-model integrating a roller pump and an arterial blood filter was filled with human blood. After heparin coating of whole circuit as well as isolated coating of arterial filter blood coagulation was less activated, but only modifying all blood contacting surfaces reduced complement activation. To examine mechanism of reduced complement activation heparin coated and unmodified surfaces were simultaneously tested in an in-vitro-study with a closed tube-circuit ("Chandler-Loop") filled with human blood. Significantly increased binding of complement inhibitors C1 Inhibitor and factor H on HBS lead to significantly reduced detection of activation specific complement proteins (iC3b and C5b-9) demonstrating reduced complement activation. Analysis of alternative C3-convertase and soluble terminal complement complex in blood revealed decreased activation for HBS. In-vivo-experiments with adult sheep compared ECMO with HBS or with unmodified surfaces for 120 hrs. Experiments demonstrated non-leaching and constant function of HBS preventing activation of coagulation and complement systems. Detection of complement proteins on HBS and unmodified surfaces confirmed results of in-vitro-experiments with "Chandler-Loop"