title: Dynamics of myosin degradation in intensive care unit-acquired weakness during severe critical illness.
abstract: OBJECTIVE
  Intensive care unit (ICU)-acquired muscle wasting is a devastating complication leading to persistent weakness and functional disability. The mechanisms of this myopathy are unclear, but a disturbed balance of myosin heavy chain (MyHC) is implicated.
  
  
  OBJECTIVE
  To investigate pathways of myosin turnover in severe critically ill patients at high risk of ICU-acquired weakness.
  
  
  METHODS
  Prospective, mechanistic, observational study.
  
  
  METHODS
  Interdisciplinary ICUs of a university hospital.
  
  
  METHODS
  Twenty-nine patients with Sequential Organ Failure Assessment (SOFA) scores of at least 8 on three consecutive days within the first 5 days in ICU underwent two consecutive open skeletal muscle biopsies from the vastus lateralis at median days 5 and 15. Control biopsy specimens were from healthy subjects undergoing hip-replacement surgery.
  
  
  METHODS
  None.
  
  
  METHODS
  Time-dependent changes in myofiber architecture, MyHC synthesis, and degradation were determined and correlated with clinical data.
  
  
  RESULTS
  ICU-acquired muscle wasting was characterized by early, disrupted myofiber ultrastructure followed by atrophy of slow- and fast-twitch myofibers at later time points. A rapid decrease in MyHC mRNA and protein expression occurred by day 5 and persisted at day 15 (P < 0.05). Expression of the atrophy genes MuRF-1 and Atrogin1 was increased at day 5 (P < 0.05). Early MuRF-1 protein content was closely associated with late myofiber atrophy and the severity of weakness.
  
  
  CONCLUSIONS
  Decreased synthesis and increased degradation of MyHCs contribute to ICU-acquired muscle wasting. The rates and time frames suggest that pathogenesis of muscle failure is initiated very early during critical illness. The persisting reduction of MyHC suggests that sustained treatment is required.
authors: Anesthesiology and Operative Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Virchow and Campus Mitte, Berlin, Germany.
authors: Tobias
authors: T
authors: Wollersheim
authors: Janine
authors: J
authors: Woehlecke
authors: Martin
authors: M
authors: Krebs
authors: Jida
authors: J
authors: Hamati
authors: Doerte
authors: D
authors: Lodka
authors: Anja
authors: A
authors: Luther-Schroeder
authors: Claudia
authors: C
authors: Langhans
authors: Kurt
authors: K
authors: Haas
authors: Theresa
authors: T
authors: Radtke
authors: Christian
authors: C
authors: Kleber
authors: Claudia
authors: C
authors: Spies
authors: Siegfried
authors: S
authors: Labeit
authors: Markus
authors: M
authors: Schuelke
authors: Simone
authors: S
authors: Spuler
authors: Joachim
authors: J
authors: Spranger
authors: Steffen
authors: S
authors: Weber-Carstens
authors: Jens
authors: J
authors: Fielitz
mesh_terms: D000328:Adult; D000368:Aged; D003422:Critical Care; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018908:Muscle Weakness / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009218:Myosins / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D009218:Myosins