Document Detail


Suppression of thrombolysis in a canine model of pulmonary embolism.
MedLine Citation:
PMID:  7994858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The brisk fibrinolytic response of canines has impaired efforts to develop a canine model of chronic thromboembolic pulmonary hypertension. Difficulties in retaining chronic embolic residuals were partially overcome by administration of tranexamic acid (TXA) (Circulation. 1991;83:1272-1279.). In this study, we used type 1 plasminogen activator inhibitor (PAI-1), a major inhibitor of the endogenous fibrinolytic system, to determine its efficacy in the suppression of thrombolysis in canines. METHODS AND RESULTS: Thrombus was induced in the inferior vena cava of anesthetized mongrel dogs with thrombin and a special double-balloon catheter; 2 hours later, the thrombus was embolized. In one group of dogs, activated type 1 plasminogen activator inhibitor (PAI-1) (130 micrograms) was delivered directly into the forming thrombus; in another, TXA (110 mg/kg) was given intravenously before thrombus formation; in controls, thrombus was induced without inhibitors. Cross-linked fibrin degradation product (D-dimer) appeared in the blood of control animals within 1 hour of thrombus induction (176 +/- 62.5 versus 1.02 +/- 0.39 ng/mL baseline; mean +/- SEM), was maximal by 4 hours (413 +/- 110 ng/mL) and remained elevated at 24 hours (90.8 +/- 19.5 ng/mL). Compared with controls, PAI-1 and TXA suppressed D-dimer release by 80% and 85%, respectively, over the first 24 hours. One week later, animals were killed, and residual emboli were harvested. Perfusion scan defects persisted in all animals at this time, but there were no scan defect differences among groups. However, emboli recovered from animals receiving PAI-1 still harbored immunoreactive PAI-1 and were, on average, more than twofold greater in mass (393 +/- 56 mg) than emboli recovered from either controls (183 +/- 76 mg) or animals receiving TXA (180 +/- 80 mg). CONCLUSIONS: Intravenous TXA and intrathrombus PAI-1 effectively suppress thrombolysis for 24 hours in canines. Thromboemboli enriched with PAI-1 appear to resist lysis for longer periods of time (up to 1 week). These findings are consistent with the hypothesis that PAI-1 remains associated with the embolus, where it continues to inhibit lysis, whereas TXA eventually diffuses out of the embolus, allowing lysis to ensue.
Authors:
J J Marsh; R G Konopka; I M Lang; H Y Wang; C Pedersen; P Chiles; C F Reilly; K M Moser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  90     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-01-17     Completed Date:  1995-01-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3091-7     Citation Subset:  AIM; IM    
Affiliation:
Pulmonary and Critical Care Division, University of California, School of Medicine, San Diego.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antifibrinolytic Agents / pharmacology*
Antigens / analysis
Dogs
Fibrin Fibrinogen Degradation Products / metabolism
Immunohistochemistry
Plasminogen Activator Inhibitor 1 / blood,  immunology,  pharmacology
Pulmonary Embolism / blood*,  pathology
Tranexamic Acid / pharmacology
Grant Support
ID/Acronym/Agency:
HL-07022/HL/NHLBI NIH HHS; HL-23584/HL/NHLBI NIH HHS; M01-RR-00827/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antifibrinolytic Agents; 0/Antigens; 0/Fibrin Fibrinogen Degradation Products; 0/Plasminogen Activator Inhibitor 1; 1197-18-8/Tranexamic Acid

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


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