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Cytochrome c oxidase dysfunction in sepsis

Levy, Richard J. MD; Deutschman, Clifford S. MS, MD, FCCM

doi: 10.1097/01.CCM.0000278604.93569.27
Scientific Reviews

Sepsis, the principal cause of death in critically ill patients, is associated with impaired oxygen extraction by tissues. One possible explanation is the development of mitochondrial dysfunction and ineffective oxygen utilization. This abnormality has been termed cytopathic hypoxia. This may be caused by an abnormality in the transport of electrons down the cytochrome chain on the mitochondrial inner membrane. In this article we review our studies on abnormalities in the function of complex IV (cytochrome oxidase), the final electron acceptor in this chain. In addition, we provide evidence that administration of cytochrome c may overcome these abnormalities and provide a novel therapeutic alternative.

From New York Medical College and Maria Fareri Children's Hospital at Westchester Medical Center, Valhalla, NY (RJL); and University of Pennsylvania School of Medicine, Philadelphia, PA (CSD).

Supported, in part, by grants 1K08GM074117-01 (RJL) and 1R01059930-07 (CSD) from the National Institutes of Health/National Institute of General Medical Sciences, Bethesda, MD.

Drs. Levy and Deutschman have disclosed that they have submitted a patent on cytochrome c.

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© 2007 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins