| C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm. | |
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MedLine Citation:
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PMID: 16078298 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Ruptured abdominal aortic aneurysm (RAAA) is associated with a systemic inflammatory response syndrome and multiple organ dysfunction. The potential role of a novel C5 complement inhibitor in attenuation of pathological complement activation and tissue injury was explored in a model of RAAA. METHODS: Anaesthetized rats were randomized to sham (control) or shock and clamp (SC) groups. Animals in the SC group underwent 1 h of haemorrhagic shock (mean arterial pressure 50 mmHg or less), 45 min of supramesenteric aortic clamping and 2 h of reperfusion. They were randomized to receive an intravenous bolus of a functionally blocking anti-C5 monoclonal antibody (C5 inhibitor), at a dose of 20 mg/kg, or saline. Lung injury was assessed by permeability to 125I-labelled albumin, tissue myeloperoxidase (MPO) activity, and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for mRNAs encoding tumour necrosis factor (TNF) alpha and interleukin (IL) 6. RESULTS: The lung permeability index was significantly increased in the SC compared with the sham group (P = 0.032); this was prevented by the C5 inhibitor (P = 0.015). Lung MPO activity was significantly increased in the SC compared with the sham group (P < 0.001), and this increase was attenuated by treatment with the C5 inhibitor (P < 0.001). Semiquantitative RT-PCR in SC group demonstrated downregulation of TNF-alpha mRNA (P = 0.050) and upregulation of IL-6 mRNA (P < 0.001), which were both prevented by the C5 inhibitor (P = 0.014 and P < 0.001 respectively). CONCLUSION: These results indicated that C5 complement inhibition can reduce shock and acute lung injury in an experimental model of RAAA. |
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Authors:
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D W Harkin; C D Marron; R P Rother; A Romaschin; B B Rubin; T F Lindsay |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The British journal of surgery Volume: 92 ISSN: 0007-1323 ISO Abbreviation: Br J Surg Publication Date: 2005 Oct |
Date Detail:
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Created Date: 2005-09-28 Completed Date: 2005-10-24 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372553 Medline TA: Br J Surg Country: England |
Other Details:
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Languages: eng Pagination: 1227-34 Citation Subset: AIM; IM |
Affiliation:
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Division of Vascular Surgery, Department of Surgery, Toronto Hospital (General Division), Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. D.W.Harkin@qub.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aortic Aneurysm, Abdominal / enzymology, immunology* Aortic Rupture / enzymology, immunology* Blood Pressure Complement Activation / immunology Complement C5 / antagonists & inhibitors* Interleukin-6 / metabolism Male Permeability Peroxidase / metabolism RNA / metabolism Random Allocation Rats Rats, Sprague-Dawley Respiratory Distress Syndrome, Adult / enzymology, immunology, prevention & control* Reverse Transcriptase Polymerase Chain Reaction Shock, Hemorrhagic / immunology, prevention & control* Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Complement C5; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 63231-63-0/RNA; EC 1.11.1.7/Peroxidase |
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