This study was supported by a VA Merit Review Grant.
Diaphragm muscle atrophy in the mouse after long-term mechanical ventilation
Article first published online: 29 JUN 2013
© 2013 Wiley Periodicals, Inc.
Muscle & Nerve
Volume 48, Issue 2, pages 272–278, August 2013
How to Cite
Tang, H., Lee, M., Khuong, A., Wright, E. and Shrager, J. B. (2013), Diaphragm muscle atrophy in the mouse after long-term mechanical ventilation. Muscle Nerve, 48: 272–278. doi: 10.1002/mus.23748
- Issue published online: 23 JUL 2013
- Article first published online: 29 JUN 2013
- Accepted manuscript online: 12 DEC 2012 05:12AM EST
- Manuscript Accepted: 4 DEC 2012
- mechanical ventilation;
- muscle atrophy
Mechanical ventilation (MV) is a life-saving measure, but full ventilator support causes ventilator-induced diaphragm atrophy (VIDA). Previous studies of VIDA have relied on human biopsies or a rat model. If MV can induce diaphragm atrophy in mice, then mechanistic study of VIDA could be explored via genetic manipulation.
We show that 18 hours of MV in mice results in a 15% loss of diaphragm weight and a 17% reduction in fiber cross-sectional area. Important catabolic cascades are activated in this mouse model: transcription of the ubiquitin ligases, atrogin and MuRF1, and the apoptotic marker, Bim, are increased; the marker of autophagy, LC3, is induced at the protein level and shows a punctate distribution in diaphragm muscle fibers.
This mouse model recapitulates the key pathophysiological findings of other models of VIDA, and it will enable the genetic manipulation required to fully explore the mechanisms underlying this important process. Muscle Nerve, 48: 272–278, 2013