The Basic Study of the Mechanism of Propofol-Related Infusion Syndrome Using a Murine Skeletal Muscle Injury Model

BACKGROUND: The pathophysiological mechanism of propofol-related infusion syndrome (PRIS) is believed to be due to the injury to the mitochondrial electron transport chain and the resultant metabolic disorders that are caused by both propofol agents and the lipid solvent. However, the mechanisms and causative factors of PRIS have not been fully elucidated. OBJECTIVES: The aim of this study was to evaluate the possibility of a research model using the culture of differentiated C2C12 cells for fundamental research of PRIS. METHODS: First, differentiated C2C12 cells were cultured accompanied by several concentrations of chemical reagents of 2,6-diisopropylphenol (2,6 DIP) or dimethyl sulfoxide (DMSO) for 60 hours and the cell death rate was examined by trypan blue staining. Second, The cells were incubated with a commercially available propofol reagent or lipid reagent for 48 hours. The supernatant fluid of the cell culture medium was gathered and the numbers of floating cells were measured by cell counter. To investigate the mitochondrial disorder by the propofol preparation, JC-1, an experiment using fluorescent reagent, was performed for the 48 hours with 100 µg/mL propofol incubation. RESULTS: The rate of cell death was increased with elevating concentrations both of chemical reagents of 2,6 DIP group and dimethyl sulfoxide group. The rates of cell death were significantly higher in the 2,6 DIP group than DMSO group. The numbers of floating cells were increased with elevating concentrations both commercially available propofol reagent and lipid reagent groups. The decreased red/green fluorescence ratio by JC-1 staining in the propofol 100µg/mL group proved an attenuated mitochondrial membrane potential. CONCLUSIONS: The dose-dependent cell damage induced by the propofol reagents and a lipid solvent may provide a proposed model as a basic experimental model for further investigations into PRIS.