Document Detail


C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm.
MedLine Citation:
PMID:  16078298     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
D W Harkin; C D Marron; R P Rother; A Romaschin; B B Rubin; T F Lindsay
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The British journal of surgery     Volume:  92     ISSN:  0007-1323     ISO Abbreviation:  Br J Surg     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-09-28     Completed Date:  2005-10-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372553     Medline TA:  Br J Surg     Country:  England    
Other Details:
Languages:  eng     Pagination:  1227-34     Citation Subset:  AIM; IM    
Affiliation:
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
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MeSH Terms
Descriptor/Qualifier:
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:
0/Complement C5; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 63231-63-0/RNA; EC 1.11.1.7/Peroxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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