Binding of tissue plasminogen activator to vascular grafts.
Tissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDMAC). Surfactant-treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyurethane bound appreciable amounts of 125I-tPA (5-30 micrograms 125I-tPA/cm2). Upon exposure to human plasma, the amount of 125I-tPA bound to the surface shows an initial drop during the first hour of incubation, followed by a slower, roughly exponential release with a t 1/2 of approximately 75 hours. Prostheses containing bound tPA show fibrinolytic activity as measured both by lysis of clots formed in vitro, and by hydrolysis of a synthetic polypeptide substrate. Prior to incubation in plasma, tPA bound to a polymer surface has an enzymic activity similar, if not identical to that of the native enzyme in buffered solution. However, exposure to plasma causes a decrease in the fibrinolytic activity of both bound tPA and enzyme released from the surface of the polymer. These data demonstrate that surfactant-treated prostheses can bind tPA, and that these chemically modified devices can act as a slow-release drug delivery system with the potential for reducing prosthesis-induced thromboembolism.
Harvey
R A
RA
Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
Kim
H C
HC
Pincus
J
J
Trooskin
S Z
SZ
Wilcox
J N
JN
Greco
R S
RS
D000941:Antigens / Q000032:analysis; D001807:Blood Vessel Prosthesis; D002863:Chromogenic Compounds; D006801:Humans; D009842:Oligopeptides; D011108:Polymers; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013499:Surface Properties; D013501:Surface-Active Agents / Q000494:pharmacology; D013916:Thrombelastography; D010959:Tissue Plasminogen Activator / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D002863:Chromogenic Compounds; D009842:Oligopeptides; D011108:Polymers; D000644:Quaternary Ammonium Compounds; D013501:Surface-Active Agents; C009543:tridodecylmethylammonium; C060237:H-norleucyl-hexahydrotyrosyl-lysine-4-nitroanilide; D010959:Tissue Plasminogen Activator