Mechanical Ventilation Induces Myokine Expression and Catabolism In Peripheral Skeletal Muscle In Pigs

Endotoxin (LPS)‐induced sepsis increases circulating cytokines which have been associated with skeletal muscle catabolism. During critical illness, it has been postulated that muscle wasting associated with mechanical ventilation (MV) occurs due to inactivity. We hypothesize that MV and sepsis promote skeletal muscle catabolism by inducing myokine production. Neonatal pigs (n=8/group) were placed in a sling system (controls) and subjected to mechanical ventilation for 9 h in the absence (MV) and presence of LPS (LPSMV). Concentrations of cytokines in plasma and TNF‐α and IL‐6 mRNA expression, fractional protein synthesis rates (FSR) and degradation signals in the longissimus dorsi muscle were determined. Compared to controls, LPS, but not MV, increased plasma TNF‐α and IL‐6 levels. In skeletal muscle, elevation of TNF‐α and IL‐6 mRNA expression occurred in MV, but not in LPSMV pigs. FSR was reduced by 22% in MV and by 32% in LPSMV pigs. Muscle α‐actin, a product of myofibrillar degradation, and MURF1 and atrogin1 protein abundance increased in response to MV, and augmented further in the presence of LPS. These findings suggest that the increase in catabolism in skeletal muscle with MV, but not sepsis, may be due to an increase in skeletal muscle myokine gene expression. NIH AR51563, NIH AR44474, and USDA 6250‐51000‐040.