title: Muscle atrophy and preferential loss of myosin in prolonged critically ill patients.
abstract: OBJECTIVE
  Muscle weakness contributes to prolonged rehabilitation and adverse outcome of critically ill patients. Distinction between a neurogenic and/or myogenic underlying problem is difficult using routine diagnostic tools. Preferential loss of myosin has been suggested to point to a myogenic component. We evaluated markers of muscle atrophy and denervation, and the myosin/actin ratio in limb and abdominal wall skeletal muscle of prolonged critically ill patients and matched controls in relation to insulin therapy and known risk factors for intensive care unit-acquired weakness.
  
  
  METHODS
  Secondary analysis of two large, prospective, single-center randomized clinical studies.
  
  
  METHODS
  University hospital surgical and medical intensive care unit.
  
  
  METHODS
  Critically ill patients and matched controls.
  
  
  METHODS
  Intensive care unit patients had been randomized to blood glucose control to 80-110 mg/dL with insulin infusion or conventional glucose management, where insulin was only administered when glucose levels rose above 215 mg/dL.
  
  
  RESULTS
  As compared with controls, rectus abdominis and vastus lateralis muscle of critically ill patients showed smaller myofiber size, decreased mRNA levels for myofibrillar proteins, increased proteolytic enzyme activities, and a lower myosin/actin ratio, virtually irrespective of insulin therapy. Increased forkhead box O1 action may have played a role. Most alterations were more severe in patients treated with corticosteroids. Duration of corticosteroid treatment, independent of duration of intensive care unit stay or other risk factors, was a dominant risk factor for a low myosin/actin ratio. The immature acetylcholine receptor subunit γ messenger RNA expression was elevated in vastus lateralis, independent of the myosin/actin ratio.
  
  
  CONCLUSIONS
  Both limb and abdominal wall skeletal muscles of prolonged critically ill patients showed downregulation of protein synthesis at the gene expression level as well as increased proteolysis. This affected myosin to a greater extent than actin, resulting in a decreased myosin/actin ratio. Muscle atrophy was not ameliorated by intensive insulin therapy, but possibly aggravated by corticosteroids.
authors.affiliation: Departments of Intensive Care Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Derde
authors.forename: Greet
authors.initials: G
authors.lastname: Hermans
authors.forename: Inge
authors.initials: I
authors.lastname: Derese
authors.forename: Fabian
authors.initials: F
authors.lastname: Güiza
authors.forename: Yvette
authors.initials: Y
authors.lastname: Hedström
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Wouters
authors.forename: Frans
authors.initials: F
authors.lastname: Bruyninckx
authors.forename: André
authors.initials: A
authors.lastname: D'Hoore
authors.forename: Lars
authors.initials: L
authors.lastname: Larsson
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
mesh_terms: D000199:Actins / Q000032:analysis / Q000378:metabolism; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D016638:Critical Illness / Q000628:therapy; D004576:Electromyography; D005260:Female; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D009218:Myosins / Q000032:analysis / Q000378:metabolism*
chemical_list: D000199:Actins; D001786:Blood Glucose; D007328:Insulin; D009218:Myosins