Propofol may adversely affect the function of mitochondria and the clinical features of propofol infusion syndrome suggest that this may be linked to propofol-related bioenergetic failure. We aimed to assess the effect of therapeutic propofol concentrations on energy metabolism in human skeletal muscle cells.
In vitro study on human skeletal muscle cells.
University research laboratories.
Patients undergoing hip surgery and healthy volunteers.
Vastus lateralis biopsies were processed to obtain cultured myotubes, which were exposed to a range of 1–10 μg/mL propofol for 96 hours.
Extracellular flux analysis was used to measure global mitochondrial functional indices, glycolysis, fatty acid oxidation, and the functional capacities of individual complexes of electron transfer chain. In addition, we used [1-14C]palmitate to measure fatty acid oxidation and spectrophotometry to assess activities of individual electron transfer chain complexes II–IV. Although cell survival and basal oxygen consumption rate were only affected by 10 μg/mL of propofol, concentrations as low as 1 μg/mL reduced spare electron transfer chain capacity. Uncoupling effects of propofol were mild, and not dependent on concentration. There was no inhibition of any respiratory complexes with low dose propofol, but we found a profound inhibition of fatty acid oxidation. Addition of extra fatty acids into the media counteracted the propofol effects on electron transfer chain, suggesting inhibition of fatty acid oxidation as the causative mechanism of reduced spare electron transfer chain capacity. Whether these metabolic in vitro changes are observable in other organs and at the whole-body level remains to be investigated.
Concentrations of propofol seen in plasma of sedated patients in ICU cause a significant inhibition of fatty acid oxidation in human skeletal muscle cells and reduce spare capacity of electron transfer chain in mitochondria.
1Department of Anaesthesia and Intensive Care of Královské Vinohrady University Hospital and The Third Faculty of Medicine, OXYLAB-Laboratory for Mitochondrial Physiology, Charles University, Prague, Czech Republic.
2Centre for Research on Diabetes, Metabolism and Nutrition of Third Faculty of Medicine, Charles University, Prague, Czech Republic.
3Laboratory for Metabolism and Bioenergetics, The Third Faculty of Medicine, Charles University, Prague, Czech Republic.
4Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
5Department of Orthopaedics and Traumatology, Královské Vinohrady University Hospital and The Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).
Supported, in part, by grants GAUK 270915, PRVOUK P 31/P 33, PROGRES Q 36/Q 37, and AZV 16-28663A.
Dr. Krajčová disclosed that material for the laboratory work was supported from funding grants (UNCE, PROGRES Q36/Q37, PRVOUK P31/P33, AZV 16-28663A, GAUK 270915). Dr. Anděl’s institution received funding from Charles University Institutional Program Prvouk P 31 and Charles University Grant Nr 270 915, and he received funding from Sanofi Diabetes, Lilly, Novo Nordisk, Astra Zeneca, Merck, BMS, Sanofi Diabetes,GSK, and MSD. Dr. Trnka’s institution received funding from Charles University. The remaining authors have disclosed that they do not have any potential conflicts of interest.
For information regarding this article, E-mail: firstname.lastname@example.org