IN VIVO EVALUATION OF A BIOMIMETIC ENDOTHELIAL SURFACE FOR EXTRACORPOREAL CIRCULATION

Abstract

The development of nonthrombogenic surfaces for extracorporeal circulation (ECC) is ongoing. Using nitric oxide (NO)-generating coatings could reduce the need for systemic heparinization during ECC and the complications associated with this therapy. An NO-generating polymer coating using a copper complex to prevent thrombosis was evaluated using a rabbit arteriovenous (AV) model. New Zealand White rabbits were placed on an AV circuit for 4 hours with an intravenous line and arterial line to maintain hemodynamic stability and collect blood samples (arterial blood gases, platelet counts, fibrinogen levels and platelet aggregometry). The custom AV circuit was constructed of 36cm Tygon® tubing with a 14GA angiocatheter (Jelco®) for left carotid artery access and a modified 10 Fr. thoracic catheter (Argyle Kendall) for drainage into the right jugular vein. The lipophilic copper complex generates NO in the presence of S-nitrosothiols and nitrites that occur naturally in blood. The copper complex was incorporated into plasticized polyvinylchloride to coat the entire circuit to generate NO at the blood-biomaterial surface. Two groups were studied: Copper (n=9) and uncoated control (n=5). The copper and control groups had a 48% and 66% reduction in platelet counts, respectively. The copper and control groups maintained 37% and 6% of baseline platelet activity, respectively. The addition of a copper NO catalyst to a polymer coating in contact with blood reduces platelet activation and thrombus formation.