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Translational Physiology

Gene expression and muscle fiber function in a porcine ICU model

¹Department of Clinical Neurophysiology, Uppsala University Hospital, Uppsala, Sweden;
²Research Center for Genetic Medicine, Children National Medical Center;
³Department of Pediatrics, The George Washington University Medical Center, Washington, District of Columbia;
⁴Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden;
⁵Department of Physiology, University of Wisconsin, Madison, Wisconsin; and
⁶Department of Anesthesiology, Karolinska Institute, Stockholm, Sweden;
⁷Department of Biobehavioral Health, Pennsylvania State University, University Park, Pennsylvania

Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to 1) the poorly understood intricate cellular and molecular networks and 2) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a 5-day period. Among the differentially regulated transcripts, extracellular matrix, energy metabolism, sarcomeric and LIM protein mRNA levels were downregulated, while ubiquitin proteasome system, cathepsins, oxidative stress responsive genes and heat shock proteins (HSP) mRNAs were upregulated. Despite 5 days of immobilization and mechanical ventilation single muscle fiber cross-sectional areas as well as the maximum force generating capacity at the single muscle fiber level were preserved. It is proposed that HSP induction in skeletal muscle is an inherent, primary, but temporary protective mechanism against protein degradation. To our knowledge, this is the first study that isolates the effect of immobilization and mechanical ventilation in an ICU condition from various other cofactors.

mechanical ventilation; immobilization; muscle function; gene expression; ubiquitin proteasome system; heat shock proteins; Lim proteins; intensive care unit