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Mitochondrial dysfunction in sepsis

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Abstract

Sepsis is an increasingly common problem, particularly among critically ill patients. Mechanisms by which sepsis induces organ dysfunction have not been elucidated. The coexisting findings (unique to sepsis) of metabolic acidosis yet increased tissue oxygen tensions suggest cellular availability but decreased use of oxygen (tissue dysoxia). Because mitochondria use more than 90% of total body oxygen consumption for adenosine triphosphate (ATP) generation, a bioenergetic abnormality is implied. Cell and animal data have shown that nitric oxide (and its metabolites), produced in considerable excess in patients with sepsis, can affect oxidative phosphorylation by inhibiting several of its component respiratory enzymes. Human data are scarce. However, in skeletal muscle biopsies taken from patients with sepsis, we have recently demonstrated a relationship between increased nitric oxide production, antioxidant depletion, reduced respiratory chain complex I activity, and low ATP levels. These findings correlated with severity of disease and outcome and support the notion that mitochondrial dysfunction resulting in bioenergetic failure may be an important factor in the pathophysiology of sepsis-associated multiorgan failure. However, a reasonable argument can be made that the reduction in energy supply could represent a last-ditch adaptive response to ongoing inflammation, resulting in a cellular shutdown analogous to hibernation that allows eventual restoration of organ function and long-term survival in patients fit enough to survive the acute phase.

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Authors and Affiliations

  1. Bloomsbury Institute of Intensive Care Medicine, Wolfson Institute of Biomedical Research, University College London, Gower Street, 1E 6BT, London, WC, UK

    Mervyn Singer MD, FRCP

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  1. David Brealey BSc, MRCP
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  2. Mervyn Singer MD, FRCP
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Brealey, D., Singer, M. Mitochondrial dysfunction in sepsis. Curr Infect Dis Rep 5, 365–371 (2003). https://doi.org/10.1007/s11908-003-0015-9

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  • DOI: https://doi.org/10.1007/s11908-003-0015-9

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