title: Fibrinolytic properties of lysine-derivatized polyethylene in contact with flowing whole blood (Chandler loop model).
abstract: This article reports on the concept of a fibrinolytic surface based on the preferential adsorption of endogenous plasminogen from blood. Data are presented indicating that such a surface, when pretreated with tissue-type plasminogen activator (tPA), is able to dissolve nascent thrombus generated in contact with flowing whole blood. Polyethylene (PE) surfaces were modified by attaching a lysine-containing polymer using photochemical methods as reported previously (McClung et al., J Biomed Mater Res 2000;49:409-414). The lysine residues were bound chemically to the polymer via the alpha-amino groups leaving the epsilon-amino groups free (epsilon-Lys surface). Control surfaces were (a) unmodified PE, (b) PE modified with the coating polymer containing no lysine, and (c) PE modified with the polymer containing lysine bound via the epsilon-amino group. The materials in tubing form were evaluated in contact with nonanticoagulated flowing human whole blood in a modified Chandler Loop experiment. They were first treated with tPA to allow activation of adsorbed plasminogen to plasmin. It was found that thrombus formation was initiated within 15-25 min (depending on donor blood) on all surfaces, as indicated by the formation of platelet aggregates. On the controls (including the lysine-containing material in which the epsilon-amino group was used in the binding reaction) thrombogenesis continued till the tubing was occluded and blood flow ceased. On the epsilon-Lys surface, thrombogenesis was interrupted at various stages depending on the donor blood; in all cases any thrombus generated was dissolved within minutes. It was shown that thrombolysis was due to the fibrinolytic action of plasmin generated at the surface and not to plasmin formed by traces of tPA released into the blood. This work provides further evidence of the efficacy of this approach to the development of a fibrinolytic surface.
authors.affiliation: Department of Chemical Engineering, McMaster University, Hamilton, Ontario, Canada.
authors.forename: W G
authors.initials: WG
authors.lastname: McClung
authors.forename: D E
authors.initials: DE
authors.lastname: Babcock
authors.forename: J L
authors.initials: JL
authors.lastname: Brash
mesh_terms: D001769:Blood / Q000187:drug effects*; D019281:Dimerization; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008239:Lysine / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D011095:Polyethylenes / Q000494:pharmacology*; D011516:Prothrombin / Q000032:analysis; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D011095:Polyethylenes; D011516:Prothrombin; D013917:Thrombin; D010959:Tissue Plasminogen Activator; D008239:Lysine