Published ahead of print on June 16, 2004, doi:10.1164/rccm.200401-042OC Am. J. Respir. Crit. Care Med., Volume 170, Number 6, September 2004, 626-632 A more recent version of this article appeared on September 15, 2004
Submitted on January 12, 2004 Assist-Control Mechanical Ventilation Attenuates Ventilator-Induced Diaphragmatic DysfunctionCatherine S.H. Sassoon1*,1 Department of Medicine, VA Long Beach Health Care System, Long Beach, CA, USA; Department of Medicine, University of California, Irvine, CA, USA, 2 Department of Medicine, University of California, Irvine, CA, USA, 3 Department of Orthopedic Surgery, University of California, Irvine, CA, USA; Department of Physiology and Biophysics, University of California, Irvine, CA, USA * To whom correspondence should be addressed. E-mail: csassoon{at}uci.edu.
Controlled mechanical ventilation induced a profound diaphragm muscle dysfunction and atrophy. Effects of diaphragmatic contractions with assisted mechanical ventilation on diaphragmatic isometric, isotonic contractile properties or the expression of Muscle Atrophy Factor-box, the gene responsible for muscle atrophy, are unknown. We hypothesize that assisted mechanical ventilation will preserve diaphragmatic force and prevent over expression of Muscle Atrophy Factor-box. Studying sedated rabbits randomized equally into controls, 3 days of assisted or controlled ventilation; we assessed in vitro diaphragmatic isometric and isotonic contractile function. The concentrations of contractile proteins, myosin heavy-chain isoform and Muscle Atrophy Factor-box mRNA were measured. Tetanic force decreased by 14% with assisted, and 48% with controlled ventilation. Maximum shortening velocity tended to increase with controlled compared to assisted ventilation and control. Peak power output decreased 20% with assisted 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. Muscle Atrophy Factor-box gene was over-expressed with controlled ventilation. We conclude that preserving diaphragmatic contractions during mechanical ventilation attenuates the force loss induced by complete inactivity, and maintains Muscle Atrophy Factor-box gene expression in control. Key words: Artificial Respiration, Diaphragm, Isometric contractions, Isotonic contractions, Muscle atrophy
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