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Abstract:
BACKGROUND:During acute respiratory distress syndrome, proinflammatory mediators inhibit natural anticoagulant factors, which alter the normal balance between coagulation and fibrinolysis leading to a procoagulant state. We hypothesize that pulmonary administration of anticoagulants might be beneficial to treat acute respiratory distress syndrome for their anticoagulant and antiinflammatory effects and reduce the risk of systemic bleeding. OBJECTIVES:Our aim is to study the effects of nebulized antithrombin (AT) and combined AT and heparin in an animal model of acute lung injury. METHODS:Acute lung injury was induced in rats by the intratracheal administration of hydrochloric acid and lipopolysaccharide. AT alone (500 IU/kg body weight) or combined with heparin (1000 IU/kg body weight) were nebulized after the injury. Control groups received saline instead. Blood, lung tissue, bronchoalveolar lavage, and alveolar macrophages (AM) isolated from bronchoalveolar lavage were collected after 48 hours and analyzed. RESULTS:Nebulized anticoagulant treatments reduced protein concentration in the lungs and decreased injury-mediated coagulation factors (tissue factor, plasminogen activator inhibitor-1, plasminogen, and fibrinogen degradation product) and inflammation (tumor necrosis factor α and interleukin 1β) in the alveolar space without affecting systemic coagulation and no bleeding. AT alone reduced fibrin deposition and edema in the lungs. Heparin did not potentiate AT coagulant effect but promoted the reduction of macrophages infiltration into the alveolar compartment. Anticoagulants reduced nuclear factor-kB downstream effectors in AM. CONCLUSIONS:Nebulized AT and heparin attenuate lung injury through decreasing coagulation and inflammation without altering systemic coagulation and no bleeding. However, combined AT and heparin did not produce a synergistic effect.
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最新影响因子:16.036 | 期刊ISSN:1538-7933 | CiteScore:3.8 |
出版周期:Monthly | 是否OA:YES | 出版年份:2003 |
期刊官方网址:http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1538-7836
自引率:7.70% | 研究方向:医学-外周血管病 |
出版地区:ENGLAND |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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The mission of the new Journal of Thrombosis and Haemostasis will be to advance science related to the important medical problems of thrombosis, bleeding disorders and vascular biology through the diffusion and exchange of information and ideas within the international research community. The Journal publishes high quality, original research reports, state-of-the art reviews, invited commentary and debate on timely topics, letters and announcements. Editors invite both laboratory and clinical reports. The Journal of Thrombosis and Haemostasis is now available in print and online.
新一期《血栓与止血》杂志的使命是通过在国际研究领域内传播和交流信息和思想,促进与血栓形成、出血障碍和血管生物学等重要医学问题有关的科学。该杂志出版高质量的原创研究报告,最新的技术评论,邀请评论和辩论及时的主题,信件和公告。编辑邀请实验室和临床报告。《血栓与止血杂志》现已出版,并可在线阅读。
大类(学科) | 小类(学科) | 学科排名 |
医学 |
HEMATOLOGY (血液学) 2区 PERIPHERAL VASCULAR DISEASE (外周血管病) 2区 |
14/71 7/65 |
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
243 | 226 | 17 |
引文计数(2018)
文献(2015-2017)
3861次引用
1015篇文献
序号 | 类别 | 排名 | 百分位 |
1 |
大类(学科):Medicine
小类(学科):Hematology
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#16/120
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