title: Influence of weaning methods on the diaphragm after mechanical ventilation in a rat model.
abstract: Mechanical ventilation (MV) is associated with diaphragm weakness, a phenomenon termed ventilator-induced diaphragmatic dysfunction. Weaning should balance diaphragmatic loading as well as prevention of overload after MV. The weaning methods pressure support ventilation (PSV) and spontaneous breathing trials (SBT) lead to gradual or intermittent reloading of a weak diaphragm, respectively. This study investigated which weaning method allows more efficient restoration of diaphragm homeostasis.
  
  
  
  Rats (n = 8 per group) received 12 h of MV followed by either 12 h of pressure support ventilation (PSV) or intermittent spontaneous breathing trials (SBT) and were compared to rats euthanized after 12 h MV (CMV) and to acutely euthanized rats (CON). Force generation, activity of calpain-1 and caspase-3, oxidative stress, and markers of protein synthesis (phosphorylated AKT to total AKT) were measured in the diaphragm.
  
  
  
  Reduction of diaphragmatic force caused by CMV compared to CON was worsened with PSV and SBT (both p < 0.05 vs. CON and CMV). Both PSV and SBT reversed oxidative stress and calpain-1 activation caused by CMV. Reduced pAKT/AKT was observed after CMV and both weaning procedures.
  
  
  
  MV resulted in a loss of diaphragmatic contractility, which was aggravated in SBT and PSV despite reversal of oxidative stress and proteolysis.
authors: Department of Intensive and Intermediate Care, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. cbruells@ukaachen.de.
authors: Christian S
authors: CS
authors: Bruells
authors: Department of Intensive and Intermediate Care, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. tbreuer@ukaachen.de.|Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany. tbreuer@ukaachen.de.
authors: Thomas
authors: T
authors: Breuer
authors: Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Karen
authors: K
authors: Maes
authors: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
authors: Ingmar
authors: I
authors: Bergs
authors: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
authors: Christian
authors: C
authors: Bleilevens
authors: Department of Intensive and Intermediate Care, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
authors: Gernot
authors: G
authors: Marx
authors: Institute of Neuropathology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors: Joachim
authors: J
authors: Weis
authors: Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors: Ghislaine
authors: G
authors: Gayan-Ramirez
authors: Department of Anaesthesiology, University Hospital of the RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
authors: Rolf
authors: R
authors: Rossaint
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003964:Diaphragm / Q000503:physiopathology*; D008297:Male; D009119:Muscle Contraction; D018384:Oxidative Stress; D011175:Positive-Pressure Respiration; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015300:Ventilator Weaning / Q000379:methods*
chemical_list: D015415:Biomarkers
keywords: Mechanical ventilation; Pressure support ventilation; Spontaneous breathing trial; Ventilator-induced diaphragmatic dysfunction; Weaning