Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury.
BACKGROUND: Critically ill patients frequently develop acute lung injury (ALI). Disturbed alveolar fibrin turnover, a characteristic feature of ALI, is the result of both activation of coagulation and inhibition of fibrinolysis. Nebulized fibrinolytic agents could exert lung-protective effects, via...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3567078?pdf=render |
| _version_ | 1817986690223964160 |
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| author | Jorrit J Hofstra Alexander D Cornet Paul J Declerck Barry Dixon Hamid Aslami Alexander P J Vlaar Joris J Roelofs Tom van der Poll Marcel Levi Marcus J Schultz |
| author_facet | Jorrit J Hofstra Alexander D Cornet Paul J Declerck Barry Dixon Hamid Aslami Alexander P J Vlaar Joris J Roelofs Tom van der Poll Marcel Levi Marcus J Schultz |
| author_sort | Jorrit J Hofstra |
| collection | DOAJ |
| description | BACKGROUND: Critically ill patients frequently develop acute lung injury (ALI). Disturbed alveolar fibrin turnover, a characteristic feature of ALI, is the result of both activation of coagulation and inhibition of fibrinolysis. Nebulized fibrinolytic agents could exert lung-protective effects, via promotion of fibrinolysis as well as anti-inflammation. METHODS: Rats were challenged intratracheally with Pseudomonas aeruginosa, resulting in pneumonia as a model for direct ALI, or received an intravenous bolus infusion of lipopolysaccharide, as a model for indirect ALI. Rats were randomized to nebulization of normal saline (placebo), recombinant tissue plasminogen activator (rtPA), or monoclonal antibodies against plasminogen activator inhibitor-type 1 (anti-PAI-1). RESULTS: Nebulized rtPA or anti-PA1-1 enhanced the bronchoalveolar fibrinolytic system, as reflected by a significant reduction of PAI-1 activity levels in bronchoalveolar lavage fluid, and a consequent increase in plasminogen activator activity (PAA) levels to supranormal values. Both treatments also significantly affected systemic fibrinolysis as reflected by a significant increase in PAA levels in plasma to supranormal levels. Neither nebulized rtPA nor anti-PA1-1 affected pulmonary inflammation. Neither treatment affected bacterial clearance of P. aeruginosa from the lungs in case of pneumonia. CONCLUSIONS: Local treatment with rtPA or anti-PA1-1 affects pulmonary fibrinolysis but not inflammation in models of direct or indirect ALI in rats. |
| first_indexed | 2024-04-14T00:12:29Z |
| format | Article |
| id | doaj.art-91b5a6d412d14a34965fb2314c9a9cb1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T00:12:29Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-91b5a6d412d14a34965fb2314c9a9cb12022-12-22T02:23:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5526210.1371/journal.pone.0055262Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury.Jorrit J HofstraAlexander D CornetPaul J DeclerckBarry DixonHamid AslamiAlexander P J VlaarJoris J RoelofsTom van der PollMarcel LeviMarcus J SchultzBACKGROUND: Critically ill patients frequently develop acute lung injury (ALI). Disturbed alveolar fibrin turnover, a characteristic feature of ALI, is the result of both activation of coagulation and inhibition of fibrinolysis. Nebulized fibrinolytic agents could exert lung-protective effects, via promotion of fibrinolysis as well as anti-inflammation. METHODS: Rats were challenged intratracheally with Pseudomonas aeruginosa, resulting in pneumonia as a model for direct ALI, or received an intravenous bolus infusion of lipopolysaccharide, as a model for indirect ALI. Rats were randomized to nebulization of normal saline (placebo), recombinant tissue plasminogen activator (rtPA), or monoclonal antibodies against plasminogen activator inhibitor-type 1 (anti-PAI-1). RESULTS: Nebulized rtPA or anti-PA1-1 enhanced the bronchoalveolar fibrinolytic system, as reflected by a significant reduction of PAI-1 activity levels in bronchoalveolar lavage fluid, and a consequent increase in plasminogen activator activity (PAA) levels to supranormal values. Both treatments also significantly affected systemic fibrinolysis as reflected by a significant increase in PAA levels in plasma to supranormal levels. Neither nebulized rtPA nor anti-PA1-1 affected pulmonary inflammation. Neither treatment affected bacterial clearance of P. aeruginosa from the lungs in case of pneumonia. CONCLUSIONS: Local treatment with rtPA or anti-PA1-1 affects pulmonary fibrinolysis but not inflammation in models of direct or indirect ALI in rats.http://europepmc.org/articles/PMC3567078?pdf=render |
| spellingShingle | Jorrit J Hofstra Alexander D Cornet Paul J Declerck Barry Dixon Hamid Aslami Alexander P J Vlaar Joris J Roelofs Tom van der Poll Marcel Levi Marcus J Schultz Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury. PLoS ONE |
| title | Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury. |
| title_full | Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury. |
| title_fullStr | Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury. |
| title_full_unstemmed | Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury. |
| title_short | Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury. |
| title_sort | nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury |
| url | http://europepmc.org/articles/PMC3567078?pdf=render |
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