Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model.
Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients that is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents, corticosteroids (CS), and sepsis for 5 days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after 5 days' exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to 5 days' exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle-specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements, and sarcomeric proteins underlying the relative sparing of cranial vs. spinal nerve innervated muscles during exposure to the ICU intervention.
Department of Neuroscience, Clinical Neurophysiology, Uppsala University, Uppsala, Sweden.
Sudhakar
S
Aare
Julien
J
Ochala
Holly S
HS
Norman
Peter
P
Radell
Lars I
LI
Eriksson
Hanna
H
Göransson
Yi-Wen
YW
Chen
Eric P
EP
Hoffman
Lars
L
Larsson
D000818:Animals; D015153:Blotting, Western; D016638:Critical Illness; D030541:Databases, Genetic; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005121:Extremities / Q000503:physiopathology*; D005260:Female; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008410:Masticatory Muscles / Q000378:metabolism / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D059748:Proteolysis; D015203:Reproducibility of Results; D012518:Sarcomeres / Q000378:metabolism; D034421:Sus scrofa; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D006360:Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; D014157:Transcription Factors