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Published ahead of print on August 5, 2004, doi:10.1164/rccm.200304-575OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 9, November 2004, 994-999

A more recent version of this article appeared on November 1, 2004
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Submitted on May 2, 2003
Accepted on August 3, 2004

Mechanical Ventilation Depresses Protein Synthesis in the Rat Diaphragm

R. Andrew Shanely1, Darin Van Gammeren1, Keith C DeRuisseau1, A. Murat Zergeroglu1, Michael J McKenzie2, Kevin E Yarasheski2, and Scott K Powers1*

1 Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA, 2 Division of Metabolism, Endocrinology and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA

* To whom correspondence should be addressed. E-mail: spowers{at}hhp.ufl.edu.

Prolonged mechanical ventilation results in diaphragmatic atrophy and contractile dysfunction in animals. We hypothesized that mechanical ventilation-induced diaphragmatic atrophy is associated with decreased synthesis of both mixed muscle protein and myosin heavy chain protein in the diaphragm. To test this postulate, adult-rats were mechanically ventilated for 6, 12, or 18 hours and diaphragmatic protein synthesis was measured in vivo. Six hours of mechanical ventilation resulted in a 30% decrease (p<0.05) in the rate of mixed-muscle protein synthesis and a 65% decrease (p<0.05) in the rate of myosin heavy chain protein synthesis; this depression in diaphragmatic protein synthesis persisted throughout 18 hours of mechanical ventilation. Real-time polymerase chain reaction analyses revealed that mechanical ventilation, in comparison to time matched controls, did not alter diaphragmatic levels of type I and IIx myosin heavy chain messenger ribonucleic acid levels in the diaphragm. These data support the hypothesis that mechanical ventilation results in a decrease in both mixed-muscle protein and myosin heavy chain protein synthesis in the diaphragm. Further, the decline in myosin heavy chain protein synthesis does not appear to be associated with a decrease in myosin heavy chain messenger ribonucleic acid.
Key words: weaning, skeletal muscle, atrophy




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