Assist-control mechanical ventilation attenuates ventilator-induced diaphragmatic dysfunction

Am J Respir Crit Care Med. 2004 Sep 15;170(6):626-32. doi: 10.1164/rccm.200401-042OC. Epub 2004 Jun 16.


Controlled mechanical ventilation induced a profound diaphragm muscle dysfunction and atrophy. The effects of diaphragmatic contractions with assisted mechanical ventilation on diaphragmatic isometric, isotonic contractile properties, or the expression of muscle atrophy factor-box (MAF-box), the gene responsible for muscle atrophy, are unknown. We hypothesize that assisted mechanical ventilation will preserve diaphragmatic force and prevent overexpression of MAF-box. Studying sedated rabbits randomized equally into control animals, those with 3 days of assisted ventilation, and those with controlled ventilation, we assessed in vitro diaphragmatic isometric and isotonic contractile function. The concentrations of contractile proteins, myosin heavy chain isoform, and MAF-box mRNA were measured. Tetanic force decreased by 14% with assisted ventilation and 48% with controlled ventilation. Maximum shortening velocity tended to increase with controlled compared with assisted ventilation and control. Peak power output decreased 20% with assisted ventilation and 41% with controlled ventilation. Contractile proteins were unchanged with either modes of ventilation; myosin heavy chain 2X mRNA tended to increase and that of 2A to decrease with controlled ventilation. MAF-box gene was overexpressed with controlled ventilation. We conclude that preserving diaphragmatic contractions during mechanical ventilation attenuates the force loss induced by complete inactivity and maintains MAF-box gene expression in control.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / analysis
  • Animals
  • Biomechanical Phenomena
  • Diaphragm / chemistry
  • Diaphragm / physiopathology*
  • Male
  • Muscle Contraction / physiology
  • Muscle Proteins / analysis
  • Muscular Atrophy / etiology
  • Muscular Atrophy / physiopathology
  • Muscular Diseases / etiology*
  • Muscular Diseases / physiopathology
  • Rabbits
  • Respiration, Artificial / adverse effects*
  • SKP Cullin F-Box Protein Ligases / analysis
  • Skeletal Muscle Myosins / analysis


  • Actins
  • Muscle Proteins
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • Skeletal Muscle Myosins