C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm

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Abstract
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. 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) α and interleukin (IL) 6. 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-α 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). These results indicated that C5 complement inhibition can reduce shock and acute lung injury in an experimental model of RAAA.
Funding Information
  • Physicians of Ontario through Physicians Services Incorporated Foundation (98-049)