title: Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy.
abstract: OBJECTIVE
  Previous workers have demonstrated that controlled mechanical ventilation results in diaphragm inactivity and elicits a rapid development of diaphragm weakness as a result of both contractile dysfunction and fiber atrophy. Limited data exist regarding the impact of pressure support ventilation, a commonly used mode of mechanical ventilation-that permits partial mechanical activity of the diaphragm-on diaphragm structure and function. We carried out the present study to test the hypothesis that high-level pressure support ventilation decreases the diaphragm pathology associated with CMV.
  
  
  METHODS
  Sprague-Dawley rats were randomly assigned to one of the following five groups:1) control (no mechanical ventilation); 2) 12 hrs of controlled mechanical ventilation (12CMV); 3) 18 hrs of controlled mechanical ventilation (18CMV); 4) 12 hrs of pressure support ventilation (12PSV); or 5) 18 hrs of pressure support ventilation (18PSV).
  
  
  RESULTS
  We carried out the following measurements on diaphragm specimens: 4-hydroxynonenal-a marker of oxidative stress, active caspase-3 (casp-3), active calpain-1 (calp-1), fiber type cross-sectional area, and specific force (sp F). Compared with the control, both 12PSV and 18PSV promoted a significant decrement in diaphragmatic specific force production, but to a lesser degree than 12CMV and 18CMV. Furthermore, 12CMV, 18PSV, and 18CMV resulted in significant atrophy in all diaphragm fiber types as well as significant increases in a biomarker of oxidative stress (4-hydroxynonenal) and increased proteolytic activity (20S proteasome, calpain-1, and caspase-3). Furthermore, although no inspiratory effort occurs during controlled mechanical ventilation, it was observed that pressure support ventilation resulted in large decrement, approximately 96%, in inspiratory effort compared with spontaneously breathing animals.
  
  
  CONCLUSIONS
  High levels of prolonged pressure support ventilation promote diaphragmatic atrophy and contractile dysfunction. Furthermore, similar to controlled mechanical ventilation, pressure support ventilation-induced diaphragmatic atrophy and weakness are associated with both diaphragmatic oxidative stress and protease activation.
authors.affiliation: Department of Applied Physiology and Kinesiology, Center for Exercise Science, University of Florida, Gainesville, FL, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Hudson
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Smuder
authors.forename: W Bradley
authors.initials: WB
authors.lastname: Nelson
authors.forename: Christian S
authors.initials: CS
authors.lastname: Bruells
authors.forename: Sanford
authors.initials: S
authors.lastname: Levine
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
mesh_terms: D000447:Aldehydes / Q000097:blood; D000818:Animals; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003964:Diaphragm / Q000503:physiopathology*; D059725:Interactive Ventilatory Support / Q000009:adverse effects*; D009119:Muscle Contraction / Q000502:physiology; D009133:Muscular Atrophy / Q000209:etiology* / Q000503:physiopathology; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*
chemical_list: D000447:Aldehydes; D016207:Cytokines; D002154:Calpain; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex; C027576:4-hydroxy-2-nonenal