title: Negative pressure ventilation and positive pressure ventilation promote comparable levels of ventilator-induced diaphragmatic dysfunction in rats.
abstract: BACKGROUND
  Mechanical ventilation is a life-saving intervention for patients with respiratory failure. Unfortunately, a major complication associated with prolonged mechanical ventilation is ventilator-induced diaphragmatic atrophy and contractile dysfunction, termed ventilator-induced diaphragmatic dysfunction (VIDD). Emerging evidence suggests that positive pressure ventilation (PPV) promotes lung damage (ventilator-induced lung injury [VILI]), resulting in the release of signaling molecules that foster atrophic signaling in the diaphragm and the resultant VIDD. Although a recent report suggests that negative pressure ventilation (NPV) results in less VILI than PPV, it is unknown whether NPV can protect against VIDD. Therefore, the authors tested the hypothesis that compared with PPV, NPV will result in a lower level of VIDD.
  
  
  METHODS
  Adult rats were randomly assigned to one of three experimental groups (n = 8 each): (1) acutely anesthetized control (CON), (2) 12 h of PPV, and (3) 12 h of NPV. Dependent measures included indices of VILI, diaphragmatic muscle fiber cross-sectional area, diaphragm contractile properties, and the activity of key proteases in the diaphragm.
  
  
  RESULTS
  Our results reveal that no differences existed in the degree of VILI between PPV and NPV animals as evidenced by VILI histological scores (CON = 0.082 ± 0.001; PPV = 0.22 ± 0.04; NPV = 0.25 ± 0.02; mean ± SEM). Both PPV and NPV resulted in VIDD. Importantly, no differences existed between PPV and NPV animals in diaphragmatic fiber cross-sectional area, contractile properties, and the activation of proteases.
  
  
  CONCLUSIONS
  These results demonstrate that NPV and PPV result in similar levels of VILI and that NPV and PPV promote comparable levels of VIDD in rats.
authors.affiliation: Department of Anesthesiology, Medical Faculty of Rhenish-Westphalian Technical University Aachen University, Aachen, Germany. cbruells@ukaachen.de
authors.forename: Christian S
authors.initials: CS
authors.lastname: Bruells
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Smuder
authors.forename: Lucy K
authors.initials: LK
authors.lastname: Reiss
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Hudson
authors.forename: William Bradley
authors.initials: WB
authors.lastname: Nelson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Wiggs
authors.forename: Kurt J
authors.initials: KJ
authors.lastname: Sollanek
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.forename: Stefan
authors.initials: S
authors.lastname: Uhlig
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
mesh_terms: D000818:Animals; D001284:Atrophy; D016207:Cytokines / Q000032:analysis; D003964:Diaphragm / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008168:Lung / Q000473:pathology; D018384:Oxidative Stress; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055397:Ventilator-Induced Lung Injury / Q000209:etiology*; D015919:Ventilators, Negative-Pressure / Q000009:adverse effects*
chemical_list: D016207:Cytokines