Skeletal muscle contractile properties and proinflammatory cytokine gene expression in human endotoxaemia

McNicol, FJ, Hoyland, JA, Cooper, RG and Carlson, GL 2010, 'Skeletal muscle contractile properties and proinflammatory cytokine gene expression in human endotoxaemia' , British Journal of Surgery, 97 (3) , pp. 434-442.

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Background: Muscle dysfunction associated with sepsis contributes to morbidity and mortality but the underlying mechanisms are unclear. This study examined whether muscle weakness relates to an intrinsic defect in contraction, or to central mechanisms associated with acute illness, and whether systemic endotoxaemia induces changes in gene expression for proinflammatory cytokines within human muscle in vivo. Methods: In this experimental study, 12 healthy men received intravenous Escherichia coli lipopolysaccharide (LPS, 4 ng/kg) or saline (control). Voluntary and electrically stimulated quadriceps contraction, and tumour necrosis factor (TNF) α mRNA expression in quadriceps muscle biopsies were studied before and after the infusion. Results: Endotoxaemia induced transient weakness of voluntary quadriceps contraction, equivalent to a 7·8 (95 per cent confidence interval 2·1 to 13·5) per cent reduction in contractile force at 180 min (P = 0·027) and a 9·0 (5·2 to 12·8) per cent reduction at 300 min (P = 0·008). Electrically stimulated contraction was unaffected. LPS administration resulted in an apparent fibre-specific induction of TNF-α mRNA. Conclusion: Endotoxaemia results in a reduction in voluntary muscle contractile force without an apparent defect in stimulated muscle contraction. Loss of volition may be a more important factor than intrinsic dysfunction in acute sepsis-associated human muscle weakness.

Item Type: Article
Journal or Publication Title: British Journal of Surgery
Publisher: Wiley Blackwell
Refereed: Yes
ISSN: 0007-1323
Depositing User: Institutional Repository
Date Deposited: 11 Sep 2014 16:26
Last Modified: 16 Feb 2022 15:46

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