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学科主题: 临床医学
题名:
Inhaled unfractionated heparin improves abnormalities of alveolar coagulation, fibrinolysis and inflammation in endotoxemia-induced lung injury rats
作者: 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
发表日期: 2013-01-20
DOI: 10.3760/cma.j.issn.0366-6999.20121412
卷: 126, 期:2, 页:318-324
收录类别: SCI
文章类型: Article
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
英文摘要:

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.

语种: 英语
所属项目编号: 2009-1014
项目资助者: Capital Medical Development Research Fund, China
WOS记录号: WOS:000319632800022
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58594
Appears in Collections:北京大学第三临床医学院_危重医学科_期刊论文

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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

Recommended Citation:
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.
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