Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy

Crit Care Med. 2012 Apr;40(4):1254-60. doi: 10.1097/CCM.0b013e31823c8cc9.


Objectives: 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).

Measurements and main 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehydes / blood
  • Animals
  • Calpain / metabolism
  • Caspase 3 / metabolism
  • Cytokines / blood
  • Diaphragm / physiopathology*
  • Interactive Ventilatory Support / adverse effects*
  • Muscle Contraction / physiology
  • Muscular Atrophy / etiology*
  • Muscular Atrophy / physiopathology
  • Oxidative Stress
  • Proteasome Endopeptidase Complex / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Respiration, Artificial / adverse effects*


  • Aldehydes
  • Cytokines
  • Calpain
  • Caspase 3
  • Proteasome Endopeptidase Complex
  • 4-hydroxy-2-nonenal