Published ahead of print on April 17, 2003, doi:10.1164/rccm.200206-541OC Am. J. Respir. Crit. Care Med., Volume 168, Number 3, August 2003, 297-304 A more recent version of this article appeared on August 1, 2003
Submitted on June 10, 2002 Early changes in rat diaphragm biology with mechanical ventilationGabor Z Racz1,1 Institute of Biochemistry, University of Szeged, Szeged, Hungary, 2 Respiratory Muscle Research Unit, Laboratory of Pneumology and Respiratory Division, Katholieke Universiteit Leuven, Leuven, Belgium, 3 Laboratory for Experimental Immunology, Katholieke Universiteit Leuven, Leuven, Belgium, 4 Laboratory of Physiology, Katholieke Universiteit Leuven, Leuven, Belgium * To whom correspondence should be addressed. E-mail: marc.decramer{at}uz.kuleuven.ac.be.
To better characterize the effects of 24h mechanical ventilation on diaphragm, the expression of myogenic transcription factors, myosin heavy chains and sarcoplasmic/endoplasmic reticulum calcium-ATPase pumps were examined in rats. In the diaphragm of mechanically ventilated animals, the mRNA of MyoD, myosin heavy chain-2a and 2b, and of sarcoplasmic/endoplasmic reticulum calcium-ATPase-1a decreased whereas myogenin mRNA increased. In the diaphragm of anesthetized and spontaneously breathing rats only the mRNA of MyoD and myosin heavy chain-2a decreased. MyoD and myogenin protein expression followed the changes at the mRNA, while the myosin heavy chain isoforms did not change. Parallel experiments involving the gastrocnemius were performed to assess the relative contribution of muscle shortening versus immobilization-induced deconditioning on muscle regulatory factor expression. Passive shortening produced no additional effects compared to immobilization-induced deconditioning. The overall changes followed a remarkably similar pattern except for MyoD protein expression which increased in the gastrocnemius and decreased in the diaphragm while its mRNA diminished in both muscles. The early alterations in the expression of muscle protein and regulatory factors may serve as underlying molecular basis for the impaired diaphragm function seen after 24h mechanical ventilation. Whether immobilization-induced deconditioning and/or passive shortening play a role in these alterations could not be fully unravelled. Key words: Mechanical ventilation, myogenic regulatory factors, myosin heavy chain, diaphragm, passive shortening
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