Early changes in rat diaphragm biology with mechanical ventilation

To better characterize the effects of 24-hour mechanical ventilation on diaphragm, the expression of myogenic transcription factors, myosin heavy chains, and sarcoplasmic/endoplasmic reticulum calcium-ATPase pumps was examined in rats. In the diaphragm of mechanically ventilated animals, the mRNA of MyoD, myosin heavy chain-2a and -2b, and 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, whereas 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 with 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 24 hours of mechanical ventilation. Whether immobilization-induced deconditioning and/or passive shortening play a role in these alterations could not be fully unraveled.