Thromb Haemost 1989; 61(01): 131-136
DOI: 10.1055/s-0038-1646541
Original Article
Schattauer GmbH Stuttgart

Binding of Tissue Plasminogen Activator to Vascular Grafts

Richard A Harvey
1   The Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
,
Hugh C Kim
2   The Department of Hematology, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
,
Jonathan Pincus
2   The Department of Hematology, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
,
Stanley Z Trooskin
3   The Department of Surgery, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
,
Josiah N Wilcox
4   The Cardiovascular Research Department, Genentech, Inc., South San Francisco, California, USA
,
Ralph S Greco
3   The Department of Surgery, Robert Wood Johnson Medical School, Piscataway, New Jersey, USA
› Author Affiliations
Further Information

Publication History

Received 15 April 1988

Accepted after revision 04 October 1988

Publication Date:
24 July 2018 (online)

Summary

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 (TDM AC). 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 t½ of appoximately 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.

 
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