Endotoxin reduces maximal oxygen consumption in hepatocytes independent of any hypoxic insult.
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.


METHODS
Prospective, controlled experimental study.


METHODS
University Laboratory.


METHODS
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.
Rosser
D M
DM
Department of Anaesthesia & Intensive Care, University Hospital, University of Birmingham, Edgbaston, UK. s.m.baker@bham.ac.uk
Manji
M
M
Cooksley
H
H
Bellingan
G
G
D002460:Cell Line; D004731:Endotoxins / Q000009:adverse effects*; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000382:microbiology* / Q000503:physiopathology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008102:Liver Circulation; D008833:Microcirculation; D010101:Oxygen Consumption; D011446:Prospective Studies; D012772:Shock, Septic / Q000378:metabolism* / Q000382:microbiology* / Q000503:physiopathology
D004731:Endotoxins