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Bortezomib partially protects the rat diaphragm from ventilator‐induced diaphragm dysfunction
Author(s) -
Agten Anouk,
Maes Karen,
Thomas Debby,
Decramer Marc,
GayanRamirez Ghislaine
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb586
Subject(s) - diaphragm (acoustics) , bortezomib , diaphragmatic breathing , medicine , mechanical ventilation , saline , endocrinology , pathology , physics , alternative medicine , acoustics , loudspeaker , multiple myeloma
Controlled mechanical ventilation leads to diaphragmatic contractile dysfunction and atrophy. Since proteolysis is enhanced in the diaphragm during controlled mechanical ventilation, we examined whether the administration of a proteasome inhibitor, Bortezomib, would have a protective effect against ventilator‐induced diaphragm dysfunction. Anesthetized rats were submitted for 24h to CMV while receiving 0.05mg/kg Bortezomib (MVB) or saline (CMV). Control rats were acutely anesthetized (C). After 24 hours, diaphragm forces were significantly decreased in the CMV group compared to C (−36%, p<0.001). Administration of Bortezomib improved the forces compared to CMV (+15%, p<0.01), but did not return to control levels. Compared to C, diaphragm cross sectional area (CSA) of the type IIx/b fibers was significantly decreased with 22% after CMV (p<0.05), while the CSA of the different fiber types in MVB remained similar to that of C. Diaphragmatic calpain activity was significantly increased (+63%, p<0.05) in CMV, but not in MVB. No differences were found in the activity of caspase‐3. These data show that the administration of Bortezomib partially protects the diaphragm from CMV‐induced diaphragm dysfunction.