ENDOTOXIN REDUCES MAXIMAL OXYGEN-CONSUMPTION IN HEPATOCYTES INDEPENDENT OF ANY HYPOXIC INSULT

Objective: The cause of the metabolic disturbances in sepsis remains u ncertain, but there is increasing evidence suggesting that haemodynami c changes are not solely responsible. We addressed the question of whe ther 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 c ontaining Hep G2 cells in suspension. The oxygen tension was measured by porphyrin phosphorescence half-life analysis. Resting OCR was measu red in control cells and after 1, 6 and 24 h of endotoxin exposure. Tn a second series of experiments, resting and maximal OCR was measured after 6 ana 24 h of endotoxin exposure and in control cells using the addition of a mitochondrial uncoupler (FCCP); this uncouples the respi ratory chain from ATP synthesis, thereby removing negative feedback an d allowing the respiratory chain to work at maximal rate. Results: End otoxin 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 increas ed at 6 h, however exposure to endotoxin for 24 h significantly reduce d maximal OCR compared to the control cells. Conclusions: Endotoxin ha s complex effects on cellular energy metabolism causing an initial ris e in the oxygen consumption rate and a significant limitation in oxyge n consumption capacity at 24 h. These complex effects would be in keep ing with the varied responses seen in patients.