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Overexpression of SOD2 in the diaphragm provides partial protection against ventilator‐induced diaphragm atrophy and contractile dysfunction.
Author(s) -
Morton Aaron B.,
Smuder Ashley J.,
Hyatt Hayden W.,
Hinkley J Matthew,
IchinosekiSekine Noriko,
Mor Andres,
Powers Scott K.
Publication year - 2018
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.2018.32.1_supplement.856.15
Subject(s) - sod2 , diaphragm (acoustics) , diaphragmatic breathing , atrophy , medicine , mechanical ventilation , superoxide dismutase , endocrinology , pathology , oxidative stress , physics , alternative medicine , acoustics , loudspeaker
Mechanical ventilation (MV) is used clinically to maintain adequate pulmonary ventilation in patients that are unable to on their own. Unfortunately, an undesired side‐effect of prolonged MV is the rapid development of diaphragmatic atrophy and contractile dysfunction, termed collectively as ventilator‐induced diaphragm dysfunction (VIDD). The development of VIDD is clinically important because diaphragmatic weakness is a primary risk factor for difficult weaning from the ventilator. While the mechanism(s) leading to VIDD are not fully understood, increased mitochondrial production of reactive oxygen species (ROS) is a requirement for the development of VIDD. In this regard, superoxide dismutase 2 (SOD2) resides in the mitochondrial matrix and operates as the first line of defense to eliminate superoxide radicals. Therefore, we tested the hypothesis that overexpression of SOD2 in diaphragm fibers will protect against VIDD. Compared to control, viral transfection (rAAV9) of the SOD2 transgene in the diaphragm resulted in a ~70% increase in SOD2 protein abundance in diaphragm fibers. This overexpression of SOD2 in the diaphragm resulted in partial protection against VIDD by diminishing MV‐induced diaphragmatic contractile dysfunction. Nonetheless, overexpression of SOD2 did not protect against MV‐induced diaphragmatic atrophy. These findings demonstrate that increased expression of SOD2 alone in the diaphragm is not sufficient to prevent MV‐induced diaphragm atrophy but does provide partial protection against MV‐induced diaphragmatic contractile dysfunction. Support or Funding Information Supported by NIH R01 AR064189 awarded to SKP This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .