Abdominal Aortic Aneurysm Research Today is a free monthly online journal that collates and summarizes the latest research about Abdominal Aortic Aneurysm, including details on aaa (abdominal aortic aneurism), cardiac disease, treatment, symptoms, surgery. | ||||||||
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C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm.Harkin DW, Marron CD, Rother RP, Romaschin A, Rubin BB, Lindsay TF 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 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. Published 28 September 2005 in Br J Surg, 92(10): 1227-34.
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