Usui 2012 Eur J Anaes
|Usui D, Isaksson M, Suzuki M, Sjovall F, Elmer E, Uchino H (2012) The influence of anesthetic agents on mitochondrial function as determined by high‐resolved respirometry of human blood cells: 9AP7‐9. Eur J Anaes 29:150.|
Abstract: Background and Goal of Study: Anesthetics have been demonstrated to inhibit mitochondrial function in animal models, an effect that could be related to neurological sequelae of prolonged or excessive anesthesia in man. It has been proposed that toxicity of anesthetic agents could be caused by inhibition of the electron transport system. In this study, using high-resolved respirometry of human blood cells, the objective was to evaluate the influence of commonly used anesthetic agents in a wide concentration range on mitochondrial oxygen consumption in platelets.
Materials and Methods: Platelets samples were isolated from healthy volunteers and were rapidly analyzed by high-resolution respirometry using an Oroboros-2k Oxygraph. Platelets were exposed to propofol (5-150 μg/mL), sevoflurane (0.4-8 mmol/L) and midazolam (0.1-20 μg/mL). Mitochondria were stimulated with complex-specific substrates and inhibitors. Statistical analysis were performed using one way ANOVA with post hoc Dunnett’s test and were compared to a separate control group (N＝20). Informed consent was received from all participants and the study was approved by the ethical committee of Tokyo Medical University.
Results and Discussion: Within the therapeutic concentration-range of the investigated agents, no apparent inhibition of respiratory capacity was noted. Rather, at therapeutic concentrations, significant increases in mitochondrial respiratory parameters were detected for sevoflurane and propofol. Dose-dependent inhibition of respiration was found in the presence of high doses of propofol (30 μg/mL and above) and sevoflurane (1.6 mmol/L and above). The respiratory inhibition was more prominent for Complex I respiration as compared to Complex II-supported respiration. For midazolam no significant effects were noted at the concentration range investigated.
Conclusion: In freshly isolated and permeabilized human platelets, the commonly used anesthetics sevoflurane and propofol stimulate mitochondrial respiratory capacity at clinically relevant concentrations. At higher concentrations, these agents displayed a dose-dependent inhibition of Complex I and II-supported respiration. The increased respiratory capacity induced by sevoflurane and propofol might be beneficial and the inhibition of respiration could be relevant to situations of prolonged or excessive exposure, especially in situations of tissue accumulation of these anesthetics.
• Keywords: Anaesthetics, Platelets
Labels: MiParea: Pharmacology;toxicology
Organism: Human Tissue;cell: Blood cells, Platelet Preparation: Permeabilized cells Enzyme: Complex I, Complex II;succinate dehydrogenase
Coupling state: ET Pathway: N, S HRR: Oxygraph-2k
JP, SE, MitoEAGLE blood cells data