title: Mitochondrial Function in an In Vitro Model of Skeletal Muscle of Patients With Protracted Critical Illness and Intensive Care Unit-Acquired Weakness.
abstract: Functional mitochondria in skeletal muscle of patients with protracted critical illness and intensive care unit-acquired weakness are depleted, but remaining mitochondria have increased functional capacities of respiratory complexes II and III. This can be an adaptation to relative abundancy of fatty acid over glucose caused by insulin resistance. We hypothesized that the capacity of muscle mitochondria to oxidize fatty acid is increased in protracted critical illness.
  
  
  
  We assessed fatty acid oxidation (FAO) and mitochondrial functional indices in vitro by using extracellular flux analysis in cultured myotubes obtained by isolating and culturing satellite cells from vastus lateralis muscle biopsy samples from patients with ICU-acquired weakness (n = 6) and age-matched healthy controls (n = 7). Bioenergetic measurements were performed at baseline and after 6 days of exposure to free fatty acids (FFAs).
  
  
  
  Mitochondrial density in myotubes from ICU patients was 69% of healthy controls ( P = .051). After adjustment to mitochondrial content, there were no differences in adenosine triphosphate (ATP) synthesis or the capacity and coupling of the respiratory chain. FAO capacity in ICU patients was 157% of FAO capacity in controls ( P = .015). In myotubes of ICU patients, unlike healthy controls, the exposure to FFA significantly ( P = .009) increased maximum respiratory chain capacity.
  
  
  
  In an in vitro model of skeletal muscle of patients with protracted critical illness, we have shown signs of adaptation to increased FAO. Even in the presence of glucose and insulin, elevation of FFAs in the extracellular environment increased maximal capacity of the respiratory chain.
authors.affiliation: 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.|2 Anaesthesiology and Resuscitation Department, Cardiology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Jiroutková
authors.affiliation: 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.|3 Department of Internal Medicine II, Kralovske Vinohrady University Hospital, Prague, Czech Republic.
authors.forename: Adéla
authors.initials: A
authors.lastname: Krajčová
authors.affiliation: 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jakub
authors.initials: J
authors.lastname: Žiak
authors.affiliation: 4 Department of Anaesthesia and Intensive Care Medicine, Královské Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Fric
authors.affiliation: 3 Department of Internal Medicine II, Kralovske Vinohrady University Hospital, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Gojda
authors.affiliation: 5 Department of Orthopaedic Surgeries, Kralovske Vinohrady University Hospital, Prague, Czech Republic.
authors.forename: Valér
authors.initials: V
authors.lastname: Džupa
authors.affiliation: 6 Department of Cell Biology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Kalous
authors.affiliation: 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Tůmová
authors.affiliation: 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Trnka
authors.affiliation: 1 Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.|4 Department of Anaesthesia and Intensive Care Medicine, Královské Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Duška
mesh_terms: D000222:Adaptation, Physiological; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D016638:Critical Illness; D004579:Electron Transport; D042963:Electron Transport Complex II / Q000378:metabolism; D004734:Energy Metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007362:Intensive Care Units; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000502:physiology*; D018485:Muscle Fibers, Skeletal; D018908:Muscle Weakness / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000503:physiopathology*; D052097:Quadriceps Muscle
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; C478189:respiratory complex II; D042963:Electron Transport Complex II
keywords: ICU-acquired weakness; extracellular flux analysis; fatty acid oxidation; human skeletal muscle; mitochondrial function; protracted critical illness