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Assist–Control Mechanical Ventilation Attenuates Ventilator-induced Diaphragmatic Dysfunction

Department of Medicine, VA Long Beach Health Care System, Long Beach; Department of Medicine and Department of Orthopedic Surgery, Physiology and Biophysics, University of California, Irvine, California

Correspondence and requests for reprints should be addressed to Catherine S. H. Sassoon, M.D., Pulmonary and Critical Care Section, VA Long Beach Healthcare System (11/111P), 5901 East 7th Street, Long Beach, CA 90822. E-mail: csassoon{at}uci.edu

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.

Key Words: artificial respiration • diaphragm • isometric contractions • isotonic contractions • muscle atrophy

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