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Bench-to-bedside review: Cytopathic hypoxia
The rate of oxygen consumption by certain tissues is impaired when mice or rats are injected with lipopolysaccharide. A similar change in the rate of oxygen consumption is observed when Caco-2 human enterocyte-like cells are incubated in vitro with cytomix, a cocktail of cytokines containing tumor n...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2002
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153437/ https://www.ncbi.nlm.nih.gov/pubmed/12493070 |
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author | Fink, Mitchell P |
author_facet | Fink, Mitchell P |
author_sort | Fink, Mitchell P |
collection | PubMed |
description | The rate of oxygen consumption by certain tissues is impaired when mice or rats are injected with lipopolysaccharide. A similar change in the rate of oxygen consumption is observed when Caco-2 human enterocyte-like cells are incubated in vitro with cytomix, a cocktail of cytokines containing tumor necrosis factor, IL-1β, and IFN-γ. The decrease in the rate of oxygen consumption is not due to a change in oxygen delivery (e.g. on the basis of diminished microvascular perfusion), but rather to an acquired intrinsic defect in cellular respiration, a phenomenon that we have termed 'cytopathic hypoxia'. A number of different biochemical mechanisms have been postulated to account for cytopathic hypoxia in sepsis, including reversible inhibition of cytochrome a,a(3) by nitric oxide, and irreversible inhibition of one or more mitochondrial respiratory complexes by peroxynitrite. Recently, however, our laboratory has obtained data to suggest that the most important mechanism underlying the development of cytopathic hypoxia is depletion of cellular stores of nicotinamide adenine dinucleotide (NAD(+)/NADH) as a result of activation of the enzyme, poly(ADP-ribose) polymerase-1. If cytopathic hypoxia is important in the pathophysiology of established sepsis and multiorgan dysfunction syndrome, then efforts in the future will need to focus on pharmacological interventions designed to preserve normal mitochondrial function and energy production in sepsis. |
format | Text |
id | pubmed-153437 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2002 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-1534372003-04-18 Bench-to-bedside review: Cytopathic hypoxia Fink, Mitchell P Crit Care Review The rate of oxygen consumption by certain tissues is impaired when mice or rats are injected with lipopolysaccharide. A similar change in the rate of oxygen consumption is observed when Caco-2 human enterocyte-like cells are incubated in vitro with cytomix, a cocktail of cytokines containing tumor necrosis factor, IL-1β, and IFN-γ. The decrease in the rate of oxygen consumption is not due to a change in oxygen delivery (e.g. on the basis of diminished microvascular perfusion), but rather to an acquired intrinsic defect in cellular respiration, a phenomenon that we have termed 'cytopathic hypoxia'. A number of different biochemical mechanisms have been postulated to account for cytopathic hypoxia in sepsis, including reversible inhibition of cytochrome a,a(3) by nitric oxide, and irreversible inhibition of one or more mitochondrial respiratory complexes by peroxynitrite. Recently, however, our laboratory has obtained data to suggest that the most important mechanism underlying the development of cytopathic hypoxia is depletion of cellular stores of nicotinamide adenine dinucleotide (NAD(+)/NADH) as a result of activation of the enzyme, poly(ADP-ribose) polymerase-1. If cytopathic hypoxia is important in the pathophysiology of established sepsis and multiorgan dysfunction syndrome, then efforts in the future will need to focus on pharmacological interventions designed to preserve normal mitochondrial function and energy production in sepsis. BioMed Central 2002 2002-09-12 /pmc/articles/PMC153437/ /pubmed/12493070 Text en Copyright © 2002 BioMed Central Ltd |
spellingShingle | Review Fink, Mitchell P Bench-to-bedside review: Cytopathic hypoxia |
title | Bench-to-bedside review: Cytopathic hypoxia |
title_full | Bench-to-bedside review: Cytopathic hypoxia |
title_fullStr | Bench-to-bedside review: Cytopathic hypoxia |
title_full_unstemmed | Bench-to-bedside review: Cytopathic hypoxia |
title_short | Bench-to-bedside review: Cytopathic hypoxia |
title_sort | bench-to-bedside review: cytopathic hypoxia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153437/ https://www.ncbi.nlm.nih.gov/pubmed/12493070 |
work_keys_str_mv | AT finkmitchellp benchtobedsidereviewcytopathichypoxia |