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Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats

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Background Acute lung injury/acute respiratory distress syndrome presents with not only local inflammation,but also pulmonary coagulopathy which is characterized by an alveolar procoagulant response,anticoagulant inhibition,fibrinolytic supression and fibrin deposition.We thus had hypothesized that if aerosolized unfractionated heparin was inhaled into alveolar spaces,it could block the procoagulant tendency,lessen depletion of coagulation factors,and even influence the inflammatory response.We also assessed the effects of different administration regimens of heparin.Methods Male Wistar rats were given inhaled heparin starting 30 minutes before (prophylactic heparin) or 2 hours after (therapeutic heparin) intravenous lipopolysaccharide (LPS) was administered at 6-hour intervals; control groups received inhaled normal saline with or without being exposed to LPS.Thrombin-antithrombin complexes,activated protein C,tissue type and urokinase type plasminogen activators (t-PNu-PA),plasminogen activator inhibitor-1 (PAl-1),tumor necrosis factor-α,interleukin-6 in bronchoalveolar lavage,and lung tissue myeloperoxidase activity,and histology score were measured at three time-points.PAI-1/(t-PA + u-PA) was calculated based on the before-mentioned parameters.Statistical analysis was made using one-way analysis of variance (ANOVA) with post hoc test or Student's t test in the case of heterogeneity of variance.Results An alveolar procoagulant reaction,depressed fibrinolysis,and inflammatory response occurred in endotoxemia-induced lung injury.Local prophylactic application of heparin attenuated coagulation and early inflammation,promoted fibrinolysis,and reduced the histology score.Therapeutic application of heparin had similar,but weaker effects.Conclusions Intrapulmonary application of unfractionated heparin by inhalation might inhibit alveolar procoagulant reaction and the early inflammatory response,promote flbrinolysis,and alleviate pulmonary pathology in endotoxemia-induced lung injury rats.Administration of heparin before LPS challenge was more efficacious.

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作者单位: Department of Intensive Care Unit, Peking University Third Hospital, Beijing 100191, China [1] Department of Cardiac Surgery, Peking University First Hospital, Beijing 100034, China [2] Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH44106-2675, USA [3] Department of Anesthesiology, Peking University People's Hospital, Beijing 100044, China [4]
期刊: 《中华医学杂志(英文版)》2013年126卷2期 318-324页 SCIMEDLINEISTICCSCDBP
栏目名称: ORIGINAL ARTICLES
DOI: 10.3760/cma.j.issn.0366-6999.20121412
发布时间: 2013-04-19
基金项目:
This study was supported by the Capital Medical Development Research Fund,China
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