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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lu, H. R. Articles by Collen, D. Search for Related Content PubMed PubMed Citation Articles by Lu, H. R. Articles by Collen, D. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Comparative thrombolytic properties of bolus injections and continuous infusions of a chimeric (t-PA/u-PA) plasminogen activator in a hamster pulmonary embolism model HR Lu, HR Lijnen, JM Stassen and D Collen Center for Thrombosis and Vascular Research, K.U. Leuven, Belgium. The recombinant chimeric plasminogen activator, rt-PA-delta FE/scu-PA- e, consisting of amino acids 1 to 3 and 87 to 274 of tissue-type plasminogen activator (t-PA) and amino acids 138 to 411 of single-chain urokinase-type plasminogen activator (scu-PA), has a markedly increased thrombolytic potency following its continuous intravenous infusion in animal models of venous thrombosis (Collen et al, Circulation, in press). In the present study, the thrombolytic potencies of intravenous bolus injections of rt-PA-delta FE/scu-PA-e, of recombinant t-PA (rt- PA), and of recombinant scu-PA (rscu-PA), given alone or in combination, were compared with those of intravenous infusions in a hamster pulmonary embolism model. Dose-dependent clot lysis was obtained in the absence of systemic activation of the fibrinolytic system and fibrinogen breakdown. In bolus injection experiments, the maximal rate of clot lysis, expressed in percent clot lysis per milligrams per kilogram compound administered, was 120 +/- 10 for rt- PA, 54 +/- 8 for rscu-PA, and 2,100 +/- 500 for rt-PA-delta FE/scu-PA-e (P less than .01 v rt-PA or rscu-PA). Comparative results with continuous infusion over 1 hour were 270 +/- 64, 99 +/- 18, and 1,500 +/- 250 (P less than .01 v rt-PA or rscu-PA) percent lysis per mg/kg compound infused for rt-PA, rscu-PA, and rt-PA-delta FE/scu-PA-e, respectively. Thus, rt-PA and rscu-PA are more potent when administered as an infusion than as a bolus, whereas rt-PA-delta FE/scu-PA-e is at least as potent when administered as a bolus. Combined bolus injections of rt-PA and rscu-PA had a 2.2-fold synergistic effect on clot lysis, but no synergism was observed with combined bolus injections or with combined infusions of rt-PA and rt-PA-delta FE/scu-PA-e, or of rscu-PA and rt-PA-delta FE/scu-PA-e. The present study thus shows that rt-PA- delta FE/scu-PA-e is much more potent for clot lysis than rt-PA or rscu- PA when administered as a bolus injection, but no synergistic interaction is observed between the chimera and either rt-PA or rscu-PA. Volume 78, Issue 1, pp. 125-131, 07/01/1991 Copyright © 1991 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-C. Murciano, D. Harshaw, D. G. Neschis, L. Koniaris, K. Bdeir, S. Medinilla, A. B. Fisher, M. A. Golden, D. B. Cines, M. T. Nakada, et al. Platelets inhibit the lysis of pulmonary microemboli Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L529 - L539. [Abstract] [Full Text] [PDF]

	Copyright © 1991 by American Society of Hematology         Online ISSN: 1528-0020