Diaphragm muscle atrophy in the mouse after long-term mechanical ventilation

Authors

  • Huibin Tang PhD,

    1. Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, VA Palo Alto Health Care System, Stanford, California, USA
    Search for more papers by this author
  • Myung Lee BA,

    1. Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, VA Palo Alto Health Care System, Stanford, California, USA
    Search for more papers by this author
  • Amanda Khuong BS,

    1. Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, VA Palo Alto Health Care System, Stanford, California, USA
    Search for more papers by this author
  • Erika Wright BS,

    1. Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, VA Palo Alto Health Care System, Stanford, California, USA
    Search for more papers by this author
  • Joseph B. Shrager MD

    Corresponding author
    • Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford School of Medicine, VA Palo Alto Health Care System, Stanford, California, USA
    Search for more papers by this author

  • This study was supported by a VA Merit Review Grant.

Correspondence to: J.B. Shrager; e-mail: shrager@stanford.edu

ABSTRACT

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 mice, 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. Muscle Nerve, 48: 272–278, 2013

Ancillary