• anesthesia
• delirium
• ketones
• lactate
• metabolism
• sleep

• Animals
• Sevoflurane
• Diet, Ketogenic
• Male
• Rats, Inbred F344
• Anesthetics, Inhalation/pharmacology
• Electroencephalography
• Glucose/metabolism
• Rats
• Prefrontal Cortex/drug effects
• Prefrontal Cortex/metabolism
• Methyl Ethers/pharmacology
• Sleep/drug effects
• Sleep/physiology
• Lactic Acid/metabolism

• R01 AG076704 NIA NIH HHS

• anesthesiology
• awareness
• delirium
• genetic differences
• genetics
• narcotics
• neuromuscular blockade
• perioperative
• postoperative nausea and vomiting (PONV)
• sex differences

• C. elegans
• ETC
• ROS
• SDH
• cancer
• electron transport chain
• healthspan
• lifespan
• reactive oxygen species
• succinate dehydrogenase

• K134285 National Research, Development and Innovation Office
• EKÖP-24-4-II-ELTE-249 EKÖP-24 University Excellence Scholarship Program of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.

• Drosophila melanogaster
• behavioral sensitivity
• complex I
• isoflurane
• mitochondria
• sevoflurane
• toxicity
• volatile anesthetics

• Animals
• Anesthetics, Inhalation/toxicity
• Anesthetics, Inhalation/pharmacology
• Electron Transport Complex I/genetics
• Drosophila melanogaster/drug effects
• Drosophila melanogaster/genetics
• Sevoflurane/pharmacology
• Mutation
• Isoflurane/toxicity
• Isoflurane/pharmacology
• Behavior, Animal/drug effects
• Mitochondria/drug effects

• RO1 GM134107 National institute of health

• Dexmedetomidine
• Ketamine
• Leigh-like
• MEGDEL syndrome
• Mitochondrial disease
• SERAC1 defect

• Child, Preschool
• Humans
• Anesthesia/methods
• Cochlear Implantation/methods
• Cochlear Implants
• Deafness/surgery
• Dexmedetomidine/therapeutic use
• Ketamine/administration & dosage

• Port Said University

• case report
• general anaesthesia
• mitochondrial disorder
• oxidative phosphorylation deficiency type 3
• paediatric

• Animals
• Caenorhabditis elegans/genetics
• Caenorhabditis elegans/drug effects
• Caenorhabditis elegans Proteins/genetics
• Mutation
• Anesthetics, Inhalation
• Electron Transport Complex I/genetics
• Electron Transport Complex I/metabolism
• Amino Acid Sequence
• Isoflurane/pharmacology

• Mitochondrial cardiomyopathy
• MitraClip™
• Percutaneous mitral valve repair
• Remimazolam

• anesthesia
• ketogenic diet
• mitochondrial disease; neurodegenerative disease

• Humans
• Child
• Child, Preschool
• Mice
• Animals
• Leigh Disease/genetics
• Isoflurane
• Diet
• Ketosis/metabolism
• Seizures
• Mitochondrial Diseases
• Anesthesia
• Anesthetics
• Electron Transport Complex I/metabolism

• R01 GM133865 NIGMS NIH HHS
• R01 GM144368 NIGMS NIH HHS
• R01 NS119426 NINDS NIH HHS
• T32 GM086270 NIGMS NIH HHS
• R35 GM139566 NIGMS NIH HHS

• Animals
• Isoflurane/toxicity
• Sevoflurane/pharmacology
• Anesthetics, Inhalation/toxicity
• Drosophila melanogaster/genetics
• Oxidative Stress
• Electron Transport Complex I/genetics
• Methyl Ethers/pharmacology

• R01 GM134107 NIGMS NIH HHS

• excitation–contraction coupling
• malignant hyperthermia
• muscle fatigue
• sarcopenia
• skeletal muscle

• Airway management
• Anesthesia care
• Blood circulation
• Knowledge mining
• Metabolism

• Humans
• Rare Diseases/diagnosis
• Anesthesia/adverse effects
• Anesthesiology
• Perioperative Care
• Anesthesiologists

• Artificial Pacemaker
• Case Report
• Idiographic Approach
• Intravenous Anaesthetics
• Kearns-Sayre Syndrome
• Oman
• Propofol

• Female
• Humans
• Adolescent
• Kearns-Sayre Syndrome
• Propofol/therapeutic use
• Dwarfism
• Oman

• electron transport chain complex I
• mitochondrial disease
• neurodegenerative disease
• paediatric disease
• toxicity

• Humans
• Animals
• Mice
• Isoflurane/toxicity
• Anesthetics, Inhalation/toxicity
• Leigh Disease/genetics
• Oxygen
• Weight Loss
• Electron Transport Complex I

• R01 GM133865 NIGMS NIH HHS
• R01 GM144368 NIGMS NIH HHS

• Anesthesia complications
• Rare disease
• Undiagnosed diseases

• Child
• Humans
• United States/epidemiology
• Anesthesiology
• Undiagnosed Diseases/etiology
• Retrospective Studies
• Anesthesia/adverse effects
• Risk Assessment
• Uridine Diphosphate

• anesthetic management
• cerebral palsy
• femoral osteotomy
• intra-iliac osteotomy
• mitochondrial disease
• slc25a46 mutation

• anesthesia
• developing brain
• mitochondria
• mitochondrial dysfunction
• neurotoxicity

• Halothane
• Isoflurane
• Ketamine
• Pentobarbital
• Propofol
• Sevoflurane

• Mice
• Animals
• Halothane/pharmacology
• Ketamine/pharmacology
• Propofol/pharmacology
• Pentobarbital
• Anesthetics, General/pharmacology
• Isoflurane/pharmacology
• Mitochondria
• Electron Transport Complex I
• Adenosine Triphosphate

• Johann Wolfgang Goethe-Universität, Frankfurt am Main (1022)

• Complex I
• anoxia
• electron transport chain
• halothane
• isoflurane
• mitochondria
• mutations
• toxicity
• volatile anesthetics

• 22q13 deletion
• Anestesia general
• Autism
• Autismo
• Deleción 22q13
• General anesthesia
• Syndrome of Phelan-McDermid
• Síndrome de Phelan-McDermid

• Female
• Humans
• Child
• Hypnotics and Sedatives
• Chromosome Disorders/complications
• Chromosome Disorders/genetics
• Chromosome Deletion
• Syndrome
• Anesthesia, General

Mitochondrial dysfunction has been linked to disease progression in COVID-19 patients. This observational pilot study aimed to assess mitochondrial function in COVID-19 patients at intensive care unit (ICU) admission (T1), seven days thereafter (T2), and in healthy controls and a general anesthesia group. Measurements consisted of in vivo mitochondrial oxygenation and oxygen consumption, in vitro assessment of mitochondrial respiration in platelet-rich plasma (PRP) and peripheral blood mononuclear cells (PBMCs), and the ex vivo quantity of circulating cell-free mitochondrial DNA (mtDNA). The median mitoVO₂ of COVID-19 patients on T1 and T2 was similar and tended to be lower than the mitoVO₂ in the healthy controls, whilst the mitoVO₂ in the general anesthesia group was significantly lower than that of all other groups. Basal platelet (PLT) respiration did not differ substantially between the measurements. PBMC basal respiration was increased by approximately 80% in the T1 group when contrasted to T2 and the healthy controls. Cell-free mtDNA was eight times higher in the COVID-T1 samples when compared to the healthy controls samples. In the COVID-T2 samples, mtDNA was twofold lower when compared to the COVID-T1 samples. mtDNA levels were increased in COVID-19 patients but were not associated with decreased mitochondrial O₂ consumption in vivo in the skin, and ex vivo in PLT or PBMC. This suggests the presence of increased metabolism and mitochondrial damage.

• COVID-19
• mitochondrial DNA
• mitochondrial function
• mitochondrial oxygen consumption
• mitochondrial oxygen tension
• mitochondrial respiration

• Leigh syndrome
• intervention
• mouse model
• pathomechanism

• Animals
• Electron Transport Complex I/genetics
• Humans
• Leigh Disease/genetics
• Mice
• Mice, Knockout
• Mitochondrial Diseases/genetics
• Oxidative Phosphorylation

• Drosophila
• Pink1
• activity
• iron
• mitochondria complex

• POLG
• mitochondrial disease
• prolonged NMB risk‐factors
• propofol infusion syndrome

Mitochondria are small cellular constituents that generate cellular energy (ATP) by oxidative phosphorylation (OXPHOS). Dysfunction of these organelles is linked to a heterogeneous group of multisystemic disorders, including diabetes, cancer, ageing-related pathologies and rare mitochondrial diseases. With respect to the latter, mutations in subunit-encoding genes and assembly factors of the first OXPHOS complex (complex I) induce isolated complex I deficiency and Leigh syndrome. This syndrome is an early-onset, often fatal, encephalopathy with a variable clinical presentation and poor prognosis due to the lack of effective intervention strategies. Mutations in the nuclear DNA-encoded NDUFS4 gene, encoding the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) of complex I, induce ‘mitochondrial complex I deficiency, nuclear type 1’ (MC1DN1) and Leigh syndrome in paediatric patients. A variety of (tissue-specific) Ndufs4 knockout mouse models were developed to study the Leigh syndrome pathomechanism and intervention testing.

Here, we review and discuss the role of complex I and NDUFS4 mutations in human mitochondrial disease, and review how the analysis of Ndufs4 knockout mouse models has generated new insights into the MC1ND1/Leigh syndrome pathomechanism and its therapeutic targeting.

• Leigh syndrome
• intervention
• mouse model
• pathomechanism

• Anaesthesia
• ENMC
• Malignant hyperthermia
• Myopathy
• Peri-operative care
• Peri-operative complication

• anesthesia
• fatty acid oxidation
• ketogenesis
• medicine
• metabolism
• mitochondria
• mouse
• neonate

Systemic anesthetic management of patients with mitochondrial disease requires careful preoperative preparation to administer adequate anesthesia and address potential disease-related complications. The appropriate general anesthetic agents to use in these patients remain controversial.

A 54-year-old woman (height, 145 cm; weight, 43 kg) diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes underwent elective cochlear implantation. Infusions of intravenous remimazolam and remifentanil guided by patient state index monitoring were used for anesthesia induction and maintenance. Neither lactic acidosis nor prolonged muscle relaxation occurred in the perioperative period. At the end of surgery, flumazenil was administered to antagonize sedation, which rapidly resulted in consciousness.

Remimazolam administration and reversal with flumazenil were successfully used for general anesthesia in a patient with mitochondrial disease.

• Flumazenil
• Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
• Mitochondrial myopathy
• Remimazolam

• Airway management
• Anesthetics
• Intraoperative monitoring
• Perioperative care
• Rare diseases

• Auxiliary liver transplant
• Glycogen storage diseases
• Liver transplantation
• Metabolic liver disease
• Pathology
• Tyrosinemia
• Urea cycle disorders
• Wilson disease

• acute
• drugs
• local anesthetics
• muscle disorders
• neurological disease
• pain
• regional

Joubert syndrome and mitochondrial disease are rare congenital diseases in which a wide range of symptoms affects multiple organs. Patients with these diseases present characteristic symptoms related to the musculoskeletal, respiratory, and neurological systems, which make it difficult for anesthesiologists to manage the patient’s airway and choose appropriate anesthetic drugs.

A 13-year-old male patient with Joubert syndrome and mitochondrial disease underwent elective surgery to insert a continuous ambulatory peritoneal dialysis catheter. Anesthesia was induced and maintained with propofol, remifentanil, and rocuronium. An I-gel was inserted to secure the airway; however, the fitting did not work properly, so the patient was intubated. The operation was completed without any major problems, and the intubated patient was transferred to the intensive care unit.

Anesthesiologists should determine the method of anesthesia and prepare for unintended complications based on a full understanding of these congenital diseases.

• Airway management
• Anesthesia, intravenous
• Cerebellar diseases
• Mitochondrial disease

• Mitochondrial neurogastrointestinal encephalomyopathy
• Rare disease
• Regional anesthesia

Mitochondrial Myopathy is a rare pathology caused by a defect in the mitochondrial DNA metabolism, leading to defects in the formation of adenosine triphosphate, in the Krebs citric acid cycle, fatty acid oxidation and oxidative phosphorylation. It is manifested by exercise intolerance, muscle fatigue on small efforts, muscle weakness, tachycardia, and difficulty breathing. There are few case reports on the operative management of adult patients suffering from mitochondrial myopathy. With this report, we intend to describe the anesthetic management of a patient with mitochondrial myopathy who underwent laparoscopic gastroplasty and outline some anesthetic considerations about this pathology.

• Anesthesia
• Case report
• Gastroplasty
• Mitochondrial myopathy
• Neuromuscular disorders

Gene therapy now provides a novel approach for treating inherited monogenetic disorders, including nuclear gene mutations associated with mitochondrial diseases. In this study, we have utilized a mouse model carrying a p.Arg389Gln mutation of the mitochondrial Ferredoxin Reductase gene (Fdxr) and treated them with neurotropic AAV-PHP.B vector loaded with the mouse Fdxr cDNA sequence. We then used immunofluorescence staining and western blot to test the transduction efficiency of this vector. Toluidine blue staining and electronic microscopy were also utilized to assess the morphology of optic and sciatic nerves, and the mitochondrial respiratory chain activity was determined as well. The AAV vector effectively transduced in the central nervous system and peripheral organs, and AAV-Fdxr treatment reversed almost all the symptoms of the mutants (Fdxr^R389Q/R389Q). This therapy also improved the electronic conductivity of the sciatic nerves, prevented optic atrophy, improved mobility, and restored mitochondrial complex function. Most notably, the sensory neuropathy, neurodegeneration, and chronic neuroinflammation in the brain were alleviated. Overall, we present the first demonstration of a potential definitive treatment that significantly improves optic and sciatic nerve atrophy, sensory neuropathy, and mitochondrial dysfunction in FDXR-related mitochondriopathy. Our study provides substantial support for the translation of AAV-based Fdxr gene therapy into clinical applications.

Regulation of synaptically located ionotropic receptors is thought to be the main mechanism by which anaesthetics cause unconsciousness. An alternative explanation, which has received much less attention, is that of primary anaesthetic disruption of brain metabolism via suppression of mitochondrial proteins. In this pilot study in mouse cortical slices, we investigated the effect of disrupting cellular metabolism on tissue oxygen handling and cortical population seizure-like event (SLE) activity, using the mitochondrial complex I inhibitor rotenone, and compared this to the effects of the general anaesthetics sevoflurane, propofol and ketamine. Rotenone caused an increase in tissue oxygen (98 mmHg to 157 mmHg (p < 0.01)) before any measurable change in SLE activity. Thereafter, tissue oxygen continued to increase and was accompanied by a significant and prolonged reduction in SLE root mean square (RMS) activity (baseline RMS of 1.7 to 0.7 µV, p < 0.001) and SLE frequency (baseline 4.2 to 0.4 events/min, p = 0.001). This temporal sequence of effects was replicated by all three anaesthetic drugs. In conclusion, anaesthetics with differing synaptic receptor mechanisms all effect changes in tissue oxygen handling and cortical network activity, consistent with a common inhibitory effect on mitochondrial function. The temporal sequence suggests that the observed synaptic depression—as seen in anaesthesia—may be secondary to a reduction in cellular metabolic capacity.

• anaesthesia
• cortex
• metabolism
• mitochondria
• mouse
• synapse

Mitochondrial dysfunction comprehends a wide range of genetic disorders. These patients' precarious metabolic balance makes its management difficult. Furthermore, the same systems affected by mitochondrial disease can be altered by many of the frequently used anesthetic agents. Each patient has to be evaluated individually according to their comorbidities and anesthetic requirements.

• DNA
• Dihydroethidium (DHE)
• GRM1
• ISO preconditioning
• ischemia
• myocardial infarction

We aim to describe the evaluation and management of a patient with the uncommon combination of both mitochondrial myopathy and possible malignant hyperthermia susceptibility as an important source of information and as a valuable example of the role of regional anesthesia for patients with these diagnoses.

A 24 year old woman with a history of possible mitochondrial myopathy and possible malignant hyperthermia susceptibility presented for gynecologic surgery. Surgery was well tolerated with combined spinal epidural anesthesia as well as sedation with midazolam, ketamine, and fentanyl.

Anesthetic management of patients with mitochondrial myopathy is challenging, made even more so with concurrent malignant hyperthermia susceptibility. This case adds an example to the literature of employing regional anesthesia as a safe approach to this complex care.

• Combined spinal epidural
• Malignant hyperthermia
• Mitochondrial myopathy
• Regional anesthesia

The selection of anesthetic agents is important in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome patient because serious and unexpected complications can occur after anesthetic exposure.

A 30-year-old man with MELAS syndrome and sepsis underwent colectomy. Propofol was administered by step-wise until target effect-site concentration (Ce) 1.0 μg/ml and stopped for the loss of consciousness and to avoid hemodynamic instability. After the loss of consciousness, total intravenous anesthesia (TIVA) using dexmedetomidine (1.0 μg/ml/h) and remifentanil (1–4 ng/ml of Ce) was performed for the maintenance of anesthesia to avoid malignant hyperthermia and mitochondrial dysfunction. During the surgery, the bispectral index score stayed between 26 and 44, and increased to 97 after the end of anesthesia.

TIVA with dexmedetomidine and remifentanil as non-triggering anesthetic agents in patients with MELAS syndrome and systemic sepsis may have advantages to decrease damages associated with mitochondrial stress and metabolic burden.

• Dexmedetomidine
• Intravenous anesthesia
• MELAS syndrome
• Remifentanil
• Sepsis

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.

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.

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.

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.

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.

• C2C12 Cell
• Mitochondria
• Propofol-Related Infusion Syndrome (PRIS)
• Rhabdomyolysis
• Skeletal Muscle