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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 Krishnamurti, C Articles by Alving, B. Search for Related Content PubMed PubMed Citation Articles by Krishnamurti, C Articles by Alving, B. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PAI-1-resistant t-PA: low doses prevent fibrin deposition in rabbits with increased PAI-1 activity C Krishnamurti, B Keyt, P Maglasang and BM Alving Department of Hematology and Vascular Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA. The present study compared the activities of recombinant tissue-type plasminogen activator (t-PA) and a plasminogen activator inhibitor-1 (PAI-1)-resistant variant t-PA (Kt-PA, KHRR 296-299 AAAA) in preventing renal fibrin deposition in rabbits with elevated PAI-1 activity. In this model, all rabbits were infused with endotoxin (10 micrograms/kg), followed by initiation of thrombin (130 U/kg) 4 hours later, when plasma PAI-1 activity was greater than 200 arbitrary units (AU)/mL (baseline, < 3 AU/mL). Thirty minutes after completion of the 1-hour thrombin infusion, rabbits were killed and the kidneys fixed and stained for identification of fibrin deposition. Rabbits received one of the following treatments initiated 30 minutes before thrombin and continued during the 1-hour thrombin infusion: (1) saline (n = 7); (2) low-dose t-PA (17 micrograms/kg, n = 4); (3) higher-dose t-PA (170 micrograms/kg, n = 4); or (4) low-dose Kt-PA (17 micrograms/kg, n = 6). Fibrin deposition occurred in 86% and 100% of the rabbits receiving saline or low-dose t-PA, respectively. Fibrin deposition did not occur in any of the rabbits receiving low-dose Kt-PA or higher-dose t-PA. Low- dose Kt-PA and higher dose t-PA also caused a reduction in fibrin deposition when infused after thrombin administration had been completed. The data provide in vivo evidence that Kt-PA is more effective than t-PA in preventing fibrin deposition in an animal model that combines thrombogenic stimulation with increased PAI-1 activity. Volume 87, Issue 1, pp. 14-19, 01/01/1996 Copyright © 1996 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: P. Carmeliet, J.-M. Stassen, I. Van Vlaenderen, R. S. Meidell, D. Collen, and R. D. Gerard Adenovirus-Mediated Transfer of Tissue-Type Plasminogen Activator Augments Thrombolysis in Tissue-Type Plasminogen Activator-Deficient and Plasminogen Activator Inhibitor-1-Overexpressing Mice Blood, August 15, 1997; 90(4): 1527 - 1534. [Abstract] [Full Text] [PDF]

	Copyright © 1996 by American Society of Hematology         Online ISSN: 1528-0020