|Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats|
|Wang Zong-yu1; Wu Sheng-nan2; Zhu Zhao-zhong3; Yang Ba-xian4; Zhu Xi1|
|关键词||acute lung injury endotoxemia heparin administration by inhalation coagulation|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||RESPIRATORY-DISTRESS-SYNDROME ; ACTIVATED PROTEIN-C ; PULMONARY COAGULATION ; HEALTHY-VOLUNTEERS ; DEPOSITION ; SEPSIS ; PROCOAGULANT ; PNEUMONIA ; CYTOKINES ; THROMBIN|
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 (PAI-1), tumor necrosis factor-a, interleukin-6 in bronchoalveolar lavage, and lung tissue nnyeloperoxidase 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 pathology in endotoxemia-induced lung injury rats. Administration of heparin before LPS challenge was more efficacious.
|资助机构||Capital Medical Development Research Fund, China|
|作者单位||1.Peking Univ, Dept Intens Care Unit, Hosp 3, Beijing 100191, Peoples R China|
2.Peking Univ, Dept Cardiac Surg, Hosp 1, Beijing 100034, Peoples R China
3.Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA
4.Peking Univ, Dept Anesthesiol, Peoples Hosp, Beijing 100044, Peoples R China
|Wang Zong-yu,Wu Sheng-nan,Zhu Zhao-zhong,et al. Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats[J]. CHINESE MEDICAL JOURNAL,2013,126(2):318-324.|
|APA||Wang Zong-yu,Wu Sheng-nan,Zhu Zhao-zhong,Yang Ba-xian,&Zhu Xi.(2013).Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats.CHINESE MEDICAL JOURNAL,126(2),318-324.|
|MLA||Wang Zong-yu,et al."Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats".CHINESE MEDICAL JOURNAL 126.2(2013):318-324.|