Document Detail


Endotoxin reduces maximal oxygen consumption in hepatocytes independent of any hypoxic insult.
MedLine Citation:
PMID:  9722044     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The cause of the metabolic disturbances in sepsis remains uncertain, but there is increasing evidence suggesting that haemodynamic changes are not solely responsible. We addressed the question of whether endotoxin has a significant effect on cellular oxygen metabolism, independent of confounding haemodynamic defects. DESIGN: Prospective, controlled experimental study. Setting: University Laboratory. MODEL: Human hepatocyte cell line. METHODS: The oxygen consumption rate (OCR) was calculated from the fall in oxygen tension in a sealed cuvette containing Hep G2 cells in suspension. The oxygen tension was measured by porphyrin phosphorescence half-life analysis. Resting OCR was measured in control cells and after 1, 6 and 24 h of endotoxin exposure. In a second series of experiments, resting and maximal OCR was measured after 6 and 24 h of endotoxin exposure and in control cells using the addition of a mitochondrial uncoupler (FCCP); this uncouples the respiratory chain from ATP synthesis, thereby removing negative feedback and allowing the respiratory chain to work at maximal rate. RESULTS: Endotoxin caused a rise in resting OCR at 1 h which was significant by 6 h but had returned to control values by 24 h. Maximal OCR also increased at 6 h, however exposure to endotoxin for 24 h significantly reduced maximal OCR compared to the control cells. CONCLUSIONS: Endotoxin has complex effects on cellular energy metabolism causing an initial rise in the oxygen consumption rate and a significant limitation in oxygen consumption capacity at 24 h. These complex effects would be in keeping with the varied responses seen in patients.
Authors:
D M Rosser; M Manji; H Cooksley; G Bellingan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Intensive care medicine     Volume:  24     ISSN:  0342-4642     ISO Abbreviation:  Intensive Care Med     Publication Date:  1998 Jul 
Date Detail:
Created Date:  1998-11-10     Completed Date:  1998-11-10     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7704851     Medline TA:  Intensive Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  725-9     Citation Subset:  IM; S    
Affiliation:
Department of Anaesthesia & Intensive Care, University Hospital, University of Birmingham, Edgbaston, UK. s.m.baker@bham.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Anoxia / metabolism*,  microbiology*,  physiopathology
Cell Line
Endotoxins / adverse effects*
Hemodynamics
Humans
Liver / cytology,  metabolism*
Liver Circulation
Microcirculation
Oxygen Consumption*
Prospective Studies
Shock, Septic / metabolism*,  microbiology*,  physiopathology
Chemical
Reg. No./Substance:
0/Endotoxins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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