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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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Chinese Medical Journal 2013年第2期126卷 318-324页

作者： WANG Zong-yu WU Sheng-nan ZHU Zhao-zhong YANG Ba-xian ZHU Xi Department of Intensive Care Unit Peking University ThirdHospital Beijing 100191 China Department of Cardiac Surgery Peking University First HospitalBeijing 100034 China Department of Biomedical Engineering Case Western ReserveUniversity Cleveland OH44106-2675 USA Department of Anesthesiology Peking University People'sHospital Beijing 100044 China

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-PA/u-PA）, plasminogen activator inhibitor-1 （PAl-l）, tumor necrosis factor-a, 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 fibrinolysis, and alleviate pulmonary

关键词： acute lung injury, endotoxemia heparin,administration by inhalation, coagulation

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