C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm.
Br J Surg
; 92(10): 1227-34, 2005 Oct.
Article
en En
| MEDLINE
| ID: mdl-16078298
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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Rotura de la Aorta
/
Síndrome de Dificultad Respiratoria
/
Choque Hemorrágico
/
Complemento C5
/
Aneurisma de la Aorta Abdominal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Br J Surg
Año:
2005
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Reino Unido