• Huibin Tang, Myung Lee, Amanda Khuong, Erika Wright, and Joseph B Shrager.
• Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, VA Palo Alto Health Care System, 300 Pasteur Drive, Stanford, California 94305-5407, USA.
• Muscle Nerve. 2013 Aug 1;48(2):272-8.

IntroductionMechanical 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.ResultsWe 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.ConclusionsThis 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.© 2013 Wiley Periodicals, Inc.

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