title: Prolonged mechanical ventilation alters diaphragmatic structure and function.
abstract: OBJECTIVE
  To review current knowledge about the impact of prolonged mechanical ventilation on diaphragmatic function and biology.
  
  
  METHODS
  Systematic literature review.
  
  
  CONCLUSIONS
  Prolonged mechanical ventilation can promote diaphragmatic atrophy and contractile dysfunction. As few as 18 hrs of mechanical ventilation results in diaphragmatic atrophy in both laboratory animals and humans. Prolonged mechanical ventilation is also associated with diaphragmatic contractile dysfunction. Studies using animal models revealed that mechanical ventilation-induced diaphragmatic atrophy is due to increased diaphragmatic protein breakdown and decreased protein synthesis. Recent investigations have identified calpain, caspase-3, and the ubiquitin-proteasome system as key proteases that contribute to mechanical ventilation-induced diaphragmatic proteolysis. The scientific challenge for the future is to delineate the mechanical ventilation-induced signaling pathways that activate these proteases and depress protein synthesis in the diaphragm. Future investigations that define the signaling mechanisms responsible for mechanical ventilation-induced diaphragmatic weakness will provide the knowledge required for the development of new medicines that can maintain diaphragmatic mass and function during prolonged mechanical ventilation.
authors.affiliation: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA. spowers@hhp.ufl.edu
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Kavazis
authors.forename: Sanford
authors.initials: S
authors.lastname: Levine
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016638:Critical Illness; D003964:Diaphragm / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009133:Muscular Atrophy / Q000209:etiology* / Q000378:metabolism* / Q000517:prevention & control; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D012307:Risk Factors; D025801:Ubiquitin / Q000378:metabolism; D015300:Ventilator Weaning / Q000379:methods
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D025801:Ubiquitin; D002154:Calpain; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex