ARS | Publication request: Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: February 24, 2010
Publication Date: April 24, 2010
Citation: Orellana, R.A., Srivastava, N., Gazzaneo, M.C., Murgas-Torrazza, R., Suryawan, A., El-Kadi, S.W., Fiorotto, M.L., Davis, T.A., Nguyen, H.V. 2010. Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs [abstract]. Federation of American Societies for Experimental Biology Conference, Session: Protein and amino acid metabolism, April 24-28, 2010, Anaheim, California. 24:740.34.

Technical Abstract: Reduced rates of skeletal muscle accretion are a prominent feature of the metabolic response to sepsis in infants and children. Septic neonates often require medical support with mechanical ventilation (MV). The combined effects of MV and sepsis in muscle have not been examined in neonates, in whom there is normally rapid growth and protein deposition in skeletal muscle. Neonatal pigs (n=5–6/group) were subjected to MV and infused with endotoxin (LPS, 0 and 10 ug/kg (–1)/hr (–1)), dextrose, and a balanced amino acid mixture. After 9 hours, fractional protein synthesis rates (FSR) and translation and degradation signals were determined in the longissimus dorsi muscle. Compared to controls, MV alone decreased FSR by 22%, and by 36% in the presence of LPS. MV decreased eIF4G/4E association by 70% and by 95% in the MV+LPS group. The abundance of the E3 ligase, MURF-1, was increased 6- and 9-fold with MV and MV+LPS respectively. These findings suggest that the MV-associated induction of catabolism in peripheral skeletal muscle in neonatal pigs occurs by inhibition of protein synthesis and stimulation of protein degradation, appears aggravated by LPS-induced sepsis, and promotes the skeletal muscle wasting associated with critical illness.