Diaphragm muscle atrophy in mouse following long-term mechanical ventilation

… Page 7 of 32 John Wiley & Sons, Inc. Muscle & Nerve Page 8. saturation were monitored
continuously with the MouseOX Plus (Starr LifeSciences Corp., Oakmont, PA) via a sensor placed
on a shaved leg. Heart rate was maintained at 320 ± 20 beats per minute. … Introduction: 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 mouse, then mechanistic study of VIDA could be explored via genetic manipulation. Results: 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. Conclusions: 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. © 2012 Wiley Periodicals, Inc.