Binding of tissue plasminogen activator to vascular grafts

R. A. Harvey, H. C. Kim, J. Pincus, S. Z. Trooskin, J. N. Wilcox, R. S. Greco

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 μg 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.

Original languageEnglish (US)
Pages (from-to)131-136
Number of pages6
JournalThrombosis and Haemostasis
Volume61
Issue number1
DOIs
StatePublished - 1989

All Science Journal Classification (ASJC) codes

  • Hematology

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