Document Detail


Fibrin-specific lysis of microthrombosis in endotoxemic rats by saruplase.
MedLine Citation:
PMID:  8122189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The dissolution by the fibrinolytic agent saruplase of microthrombi due to disseminated intravascular coagulation (DIC) has been studied in anesthetized rats. The intravenous infusion of E. coli lipopolysaccharide (endotoxin) for 4 hours (total dose: 25 mg/kg) induced marked thrombocytopenia and hypofibrinogenemia. DIC-related microthrombosis, detected as increased deposition of 125I-labelled human fibrin, was found in the liver and the kidneys, but not in the lungs, the heart, the mesenterium, the spleen and the M. rectus abdominis of endotoxemic rats. Treatment with 1-20 micrograms/kg.min saruplase, that was infused concomitantly with endotoxin, dose-dependently and significantly reduced endotoxin-induced microthrombosis in the liver and the kidneys by 85 resp. 88%. When saruplase (20 micrograms/kg.min) was administered only during the last two hours of endotoxin infusion, liver microthrombosis was still significantly dissolved by 69%, whereas renal microthrombosis was insignificantly reduced by 34%. The inhibition of endotoxin-induced microthrombosis took place in the same dosage range as the shortening of the euglobulin clot lysis time in normal rats by saruplase as a measure of its fibrinolytic activity. Saruplase did not modify thrombocytopenia and hypofibrinogenemia in endotoxemic rats. Saruplase per se did not affect plasma fibrinogen levels. Thus, in a fibrin-selective dose range saruplase is able to dissolve microthrombosis associated with DIC in endotoxemic rats.
Authors:
J Schneider
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Thrombosis research     Volume:  72     ISSN:  0049-3848     ISO Abbreviation:  Thromb. Res.     Publication Date:  1993 Oct 
Date Detail:
Created Date:  1994-04-07     Completed Date:  1994-04-07     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  71-82     Citation Subset:  IM    
Affiliation:
Grünenthal GmbH, Center of Research, Aachen, FRG.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disseminated Intravascular Coagulation / drug therapy*,  etiology
Endotoxins / toxicity
Fibrin / analysis,  drug effects*
Fibrinogen / metabolism,  pharmacokinetics
Male
Organ Specificity
Platelet Count
Rats
Rats, Wistar
Recombinant Proteins / therapeutic use
Shock, Septic / complications*
Specific Pathogen-Free Organisms
Thrombolytic Therapy*
Tissue Distribution
Urokinase-Type Plasminogen Activator / therapeutic use*
Chemical
Reg. No./Substance:
0/Endotoxins; 0/Recombinant Proteins; 67924-63-4/endotoxin, Escherichia coli; 9001-31-4/Fibrin; 9001-32-5/Fibrinogen; 99149-95-8/saruplase; EC 3.4.21.73/Urokinase-Type Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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