Nebulized Fibrinolytic Agents Improve Pulmonary Fibrinolysis but Not Inflammation in Rat Models of Direct and Indirect Acute Lung Injury

Journal article

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

Authors: Hofstra, JJ; Cornet, AD; Declerck, PJ; Dixon, B; Aslami, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Public Library of Science
• Journal: PLoS ONE
• Volume: 8
• Issue: 2
• Pages: e55262-e55262
• Publication date: 2013-02-07
• DOI: 10.1371/journal.pone.0055262
• EISSN: 1932-6203
• ISSN: 1932-6203
• Language: English
• Keywords: Fibrinolysis; Internal medicine; Lung; Immunology; Plasminogen activator; Medicine; Tissue plasminogen activator; Fibrin; Anesthesia; Pharmacology; Bronchoalveolar lavage; Inflammation