title: Sevoflurane exposure prevents diaphragmatic oxidative stress during mechanical ventilation but reduces force and affects protein metabolism even during spontaneous breathing in a rat model.
abstract: BACKGROUND
  Ventilator-induced diaphragmatic dysfunction is associated with the generation of oxidative stress, enhanced proteolysis, autophagy and reduced protein synthesis in the diaphragm. Sevoflurane is a common operating room anesthetic and can be used in the intensive care medicine as well. Besides its anesthetic properties, its use in cardiac ischemia-reperfusion models can maintain protein synthesis and inhibit generation of reactive oxygen species, if used at the beginning of heart surgery. This study has been performed on the hypothesis that sevoflurane might protect against ventilator-induced diaphragmatic dysfunction by preventing the production of oxidative stress.
  
  
  METHODS
  Four-month-old, male Sprague-Dawley rats sedated with sevoflurane (minimal alveolar concentration = 1) were either mechanically ventilated (MV) for 12 hours (n = 8) or allowed to breathe spontaneously (SB) for 12 hours (n = 8). An acutely anesthetized group was used as a control (Con) group (n = 8). After euthanization, diaphragmatic contractile properties, fiber cross-sectional areas, proteolysis (calpain-1 and caspase-3), and oxidative stress (lipid peroxidation, protein oxidation) were examined. After testing for normality, 1-way or 2-way analysis of variance with the Dunnett post hoc test was used to test for significance.
  
  
  RESULTS
  The diaphragm contractile force was similarly reduced at all stimulation frequencies in the SB and MV groups compared with controls. Markers of oxidative stress and fiber cross-sectional areas were unaltered between Con and SB/MV, respectively. The calcium-dependent proteases (calpain-1 and caspase-3) were enhanced in the MV group. The p-AKT/AKT ratio and p-FoxO1/FoxO1 ratio were significantly and similarly reduced after sevoflurane exposure in the SB and MV group compared with Con group.
  
  
  CONCLUSIONS
  Exposure to sevoflurane did not induce oxidative stress. It led to reduction in diaphragmatic force. In the MV group, sevoflurane led to the activation of atrophy signaling pathways. These findings are of particular importance for clinical utilization in intensive care units and question its use, especially during the phases of SB.
authors: From the Department of Anesthesiology, University Hospital of the RWTH Aachen, Aachen, Germany; Laboratory of Pneumology, Katholieke Universiteit Leuven, Leuven, Belgium; and Department of Intensive and Intermediate Care, University Hospital of the RWTH Aachen, Aachen, Germany.
authors: Thomas
authors: T
authors: Breuer
authors: Karen
authors: K
authors: Maes
authors: Rolf
authors: R
authors: Rossaint
authors: Gernot
authors: G
authors: Marx
authors: Hans
authors: H
authors: Scheers
authors: Ingmar
authors: I
authors: Bergs
authors: Christian
authors: C
authors: Bleilevens
authors: Ghislaine
authors: G
authors: Gayan-Ramirez
authors: Christian S
authors: CS
authors: Bruells
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000633:toxicity*; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003964:Diaphragm / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000378:metabolism*; D053580:Muscle Strength / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D000071161:Forkhead Box Protein O1
chemical_list: D018685:Anesthetics, Inhalation; D000975:Antioxidants; D002154:Calpain; D053148:Caspase 3; D051858:Forkhead Transcription Factors; D008738:Methyl Ethers; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D000077149:Sevoflurane; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C505410:Casp3 protein, rat