Lysine-derivatized polyurethane as a clot lysing surface: conversion of adsorbed plasminogen to plasmin and clot lysis in vitro.
Polyurethane surfaces to which lysine residues are immobilized by photochemical methods are proposed as a basis for clot lysing surfaces. The lysines are attached in such a way that the epsilon-amino and carboxyl groups are free. We showed previously that these surfaces, when placed in contact with plasma, adsorb only plasminogen and virtually no other proteins (McClung et al., J. Biomed. Mater. Res. 49 (2000) 409). In this communication, data based on a chromogenic substrate assay are presented showing that plasminogen adsorbed to these surfaces is readily converted to plasmin in the presence of tissue-plasminogen activator (t-PA). Moreover, the rate of activation on the surface is considerably greater than in solution. Experiments demonstrating the ability of these surfaces to dissolve fibrin clots are also reported. Surfaces exposed to plasma and then to t-PA were placed in citrated plasma. On recalcification, clotting was initiated, but the incipient clots were soon dissolved. On control surfaces (no lysine or lysine in which the epsilon-amino groups were not available) coagulation continued until a stable clot was formed. Similar observations were made when the plasma/t-PA exposed surfaces were placed in a pure fibrinogen solution and thrombin was added.
McClung
W G
WG
Department of Chemical Engineering, McMaster University, Hamilton, Ont., Canada.
Clapper
D L
DL
Hu
S P
SP
Brash
J L
JL
D000327:Adsorption; D003124:Colorimetry; D005341:Fibrinolysin / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry*; D010958:Plasminogen / Q000378:metabolism*; D011140:Polyurethanes / Q000737:chemistry / Q000494:pharmacology*; D013499:Surface Properties
D005343:Fibrinolytic Agents; D011140:Polyurethanes; D010958:Plasminogen; D005341:Fibrinolysin; D008239:Lysine