Department 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.
Centre for Research on Diabetes, Metabolism and Nutrition of Third Faculty of Medicine, Charles University, Prague, Czech Republic.
Crit Care Med. 2018 Mar;46(3):e206-e212. doi: 10.1097/CCM.0000000000002875.
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-C]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.
丙泊酚可能会影响线粒体的功能，而丙泊酚输注综合征的临床特征表明，这可能与丙泊酚相关的生物能量衰竭有关。本研究旨在评估治疗浓度的丙泊酚对人骨骼肌细胞能量代谢的影响。
人骨骼肌细胞的体外研究。
大学研究实验室。
接受髋关节手术的患者和健康志愿者。
对股外侧肌活检进行处理，以获得培养的肌管，然后将其暴露于 1-10μg/ml 的丙泊酚中 96 小时。
采用细胞外通量分析测量整体线粒体功能指数、糖酵解、脂肪酸氧化以及电子传递链各复合体的功能能力。此外，我们还使用 [1-C]棕榈酸来测量脂肪酸氧化，并用分光光度法评估单个电子传递链复合体 II-IV 的活性。虽然只有 10μg/ml 的丙泊酚才会影响细胞存活和基础耗氧量，但浓度低至 1μg/ml 就会降低备用电子传递链的能力。丙泊酚的解偶联作用轻微，且不依赖于浓度。低剂量丙泊酚对任何呼吸复合物均无抑制作用，但我们发现其对脂肪酸氧化有显著抑制作用。向培养基中添加额外的脂肪酸可以抵消丙泊酚对电子传递链的影响，这表明抑制脂肪酸氧化是备用电子传递链能力降低的原因。这些代谢的体外变化是否在其他器官和全身水平上可见，仍有待研究。
在 ICU 镇静患者的血浆中观察到的丙泊酚浓度会导致人骨骼肌细胞中脂肪酸氧化显著抑制，并降低线粒体中电子传递链的备用能力。
