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Title: N-Acetylcysteine protects the rat diaphragm from the decreased contractility associated with controlled mechanical ventilation
Authors: Agten, Anouk ×
Maes, Karen
Smuder, Ashley
Powers, Scott K
Decramer, Marc
Gayan-Ramirez, Ghislaine #
Issue Date: Apr-2011
Publisher: Williams & Wilkins Co.
Series Title: Critical Care Medicine vol:39 issue:4 pages:777-782
Abstract: OBJECTIVE:: Controlled mechanical ventilation results in diaphragmatic dysfunction, and oxidative stress has been shown to be an important contributor to ventilator-induced diaphragm dysfunction. We hypothesized that the administration of an antioxidant, N-acetylcysteine, would restore the redox balance in the diaphragm and prevent against the deleterious effects of controlled mechanical ventilation. DESIGN:: Randomized, controlled experiment. SETTINGS:: Basic science animal laboratory. SUBJECTS:: Male Wistar rats, 14 wks old. INTERVENTIONS:: Anesthetized rats were submitted for 24 hrs to either spontaneous breathing receiving 150 mg/kg N-acetylcysteine (SBNAC) or saline (SBSAL) or to controlled mechanical ventilation receiving 150 mg/kg N-acetylcysteine (MVNAC) or saline (MVSAL). MEASUREMENTS AND MAIN RESULTS:: After 24 hrs of controlled mechanical ventilation, diaphragmatic force production was significantly lower in MVSAL compared with all groups. Importantly, administration of N-acetylcysteine completely abolished this controlled mechanical ventilation-induced diaphragmatic contractile dysfunction. Diaphragmatic protein oxidation was significantly increased after 24 hrs of controlled mechanical ventilation (+53%, p < .01) in MVSAL animals, whereas administration of N-acetylcysteine prevented this controlled mechanical ventilation-induced oxidative stress. Diaphragmatic 20S proteasome activity was increased in MVSAL (+62%, p < .05). Further, compared with SBSAL, diaphragm caspase-3 activity was significantly increased in MVSAL (+279%, p < .001), and N-acetylcysteine treatment provided partial protection against caspase-3 activation (MVNAC = +158.5%, p < .01). Diaphragmatic calpain activity was significantly increased after controlled mechanical ventilation (+137%, p < .001) in MVSAL animals, but N-acetylcysteine treatment protected against this event. Finally, significant negative correlations existed between calpain activity and diaphragm force production (r from -0.56 to -0.49, p < .05). CONCLUSIONS:: These data show that the administration of N-acetylcysteine protects the diaphragm from the deleterious effects of controlled mechanical ventilation. Specifically, N-acetylcysteine prevents against controlled mechanical ventilation-induced diaphragmatic oxidative stress and proteolysis and abolishes controlled mechanical ventilation-induced diaphragmatic contractile dysfunction.
ISSN: 0090-3493
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Pneumology
× corresponding author
# (joint) last author

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