title: Mitochondrial function in skeletal muscle of patients with protracted critical illness and ICU-acquired weakness.
abstract: BACKGROUND
  Mitochondrial damage occurs in the acute phase of critical illness, followed by activation of mitochondrial biogenesis in survivors. It has been hypothesized that bioenergetics failure of skeletal muscle may contribute to the development of ICU-acquired weakness. The aim of the present study was to determine whether mitochondrial dysfunction persists until protracted phase of critical illness.
  
  
  METHODS
  In this single-centre controlled-cohort ex vivo proof-of-concept pilot study, we obtained vastus lateralis biopsies from ventilated patients with ICU-acquired weakness (n = 8) and from age and sex-matched metabolically healthy controls (n = 8). Mitochondrial functional indices were measured in cytosolic context by high-resolution respirometry in tissue homogenates, activities of respiratory complexes by spectrophotometry and individual functional capacities were correlated with concentrations of electron transport chain key subunits from respiratory complexes II, III, IV and V measured by western blot.
  
  
  RESULTS
  The ability of aerobic ATP synthesis (OXPHOS) was reduced to ~54% in ICU patients (p<0.01), in correlation with the depletion of complexes III (~38% of control, p = 0.02) and IV (~26% of controls, p<0.01) and without signs of mitochondrial uncoupling. When mitochondrial functional indices were adjusted to citrate synthase activity, OXPHOS and the activity of complexes I and IV were not different, whilst the activities of complexes II and III were increased in ICU patients 3-fold (p<0.01) respectively 2-fold (p<0.01).
  
  
  CONCLUSIONS
  Compared to healthy controls, in ICU patients we have demonstrated a ~50% reduction of the ability of skeletal muscle to synthetize ATP in mitochondria. We found a depletion of complex III and IV concentrations and relative increases in functional capacities of complex II and glycerol-3-phosphate dehydrogenase/complex III.
authors.affiliation: Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague, 100 00, Prague 10, Czech Republic. katka.nova@post.cz.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Jiroutková
authors.affiliation: Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague, 100 00, Prague 10, Czech Republic. adela.krajcova@seznam.cz.|Department of Internal Medicine II, Kralovske Vinohrady University Hospital, Prague, Czech Republic. adela.krajcova@seznam.cz.
authors.forename: Adéla
authors.initials: A
authors.lastname: Krajčová
authors.affiliation: Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague, 100 00, Prague 10, Czech Republic. jakub.student@gmail.com.
authors.forename: Jakub
authors.initials: J
authors.lastname: Ziak
authors.affiliation: Department of Anaesthesia and Intensive Care, Kralovske Vinohrady University Hospital, Prague, Czech Republic. michalfric@seznam.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Fric
authors.affiliation: Department of Anaesthesia and Intensive Care, Kralovske Vinohrady University Hospital, Prague, Czech Republic. petrwaldauf@gmail.com.
authors.forename: Petr
authors.initials: P
authors.lastname: Waldauf
authors.affiliation: Department of Orthopaedic Surgery, Kralovske Vinohrady University Hospital, Prague, Czech Republic. dzupa@fnkv.cz.
authors.forename: Valér
authors.initials: V
authors.lastname: Džupa
authors.affiliation: Department of Internal Medicine II, Kralovske Vinohrady University Hospital, Prague, Czech Republic. jan.gojda@seznam.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Gojda
authors.affiliation: Department of Cell and Molecular Biology & Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. vlasta.furstova@tiscali.cz.
authors.forename: Vlasta
authors.initials: V
authors.lastname: Němcova-Fürstová
authors.affiliation: Department of Cell and Molecular Biology & Center for Research of Diabetes, Metabolism and Nutrition, Third Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. jan.kovar@lf3.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Kovář
authors.affiliation: Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague, 100 00, Prague 10, Czech Republic. moustafa.elkalaf@gmail.com.
authors.forename: Moustafa
authors.initials: M
authors.lastname: Elkalaf
authors.affiliation: Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague, 100 00, Prague 10, Czech Republic. jan.trnka@lf3.cuni.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Trnka
authors.affiliation: Laboratory of Bioenergetics, Third Faculty of Medicine, Charles University in Prague, Ruská 87, Prague, 100 00, Prague 10, Czech Republic. fduska@yahoo.com.|Adult Intensive Care Unit, Queen's Medical Centre, Nottingham University Hospital NHS Trust, Nottingham, UK. fduska@yahoo.com.
authors.forename: František
authors.initials: F
authors.lastname: Duška
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D016638:Critical Illness; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018908:Muscle Weakness / Q000209:etiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D001678:Organelle Biogenesis; D018384:Oxidative Stress / Q000502:physiology; D010865:Pilot Projects; D052097:Quadriceps Muscle / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D005993:Glycerolphosphate Dehydrogenase