| Tissue factor and thrombin mediate myocardial ischemia-reperfusion injury. | |
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MedLine Citation:
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PMID: 12607707 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Reperfusion of the ischemic heart is necessary to prevent irreversible injury of the myocardium, which leads to permanent organ dysfunction. However, reperfusion in itself leads to myocardial ischemia/reperfusion (I/R) injury, which is characterized by an acute inflammatory response mediated by activated inflammatory cells, chemokines, cytokines, and adhesion molecules. The molecular mechanisms of myocardial I/R injury are not completely known. Tissue factor (TF) and thrombin, two potent procoagulant and proinflammatory mediators, are recognized to play significant roles in myocardial I/R injury. To investigate the role of TF and thrombin in myocardial I/R injury, we used rabbit and murine in situ coronary artery ligation models. Increased TF mRNA, antigen, and activity were found in ischemic cardiomyocytes. Administration of an inhibitory antirabbit TF monoclonal antibody before or during the onset of ischemia resulted in a significant reduction in infarct size. Functional inhibition of thrombin with hirudin also reduced the infarct size. However, defibrinogenating rabbits with ancrod had no effect on infarct size, suggesting a requirement of thrombin generation but not fibrin deposition in myocardial I/R injury. |
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Authors:
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Albert J Chong; Timothy H Pohlman; Craig R Hampton; Akira Shimamoto; Nigel Mackman; Edward D Verrier |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: The Annals of thoracic surgery Volume: 75 ISSN: 0003-4975 ISO Abbreviation: Ann. Thorac. Surg. Publication Date: 2003 Feb |
Date Detail:
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Created Date: 2003-02-27 Completed Date: 2003-03-17 Revised Date: 2005-11-16 |
Medline Journal Info:
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Nlm Unique ID: 15030100R Medline TA: Ann Thorac Surg Country: United States |
Other Details:
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Languages: eng Pagination: S649-55 Citation Subset: AIM; IM |
Affiliation:
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Division of Cardiothoracic Surgery, The University of Washington, Seattle, Washington 98104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Ancrod
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pharmacology Animals Antibodies, Monoclonal / pharmacology Disease Models, Animal Fibrinolytic Agents / pharmacology Hirudins / pharmacology Mice Mice, Knockout Myocardial Reperfusion Injury / pathology, physiopathology* Myocardium / ultrastructure RNA, Messenger / analysis Rabbits Receptor, PAR-1 Receptors, Thrombin / physiology Thrombin / physiology* Thromboplastin / physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Fibrinolytic Agents; 0/Hirudins; 0/RNA, Messenger; 0/Receptor, PAR-1; 0/Receptors, Thrombin; 9035-58-9/Thromboplastin; EC 3.4.21.-/Ancrod; EC 3.4.21.5/Thrombin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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