Location: Children's Nutrition Research CenterTitle: Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs Author
Submitted to: Pediatric Academic Society
Publication Type: Abstract Only
Publication Acceptance Date: 11/18/2009
Publication Date: 5/1/2010
Citation: Orellana, R.A., Srivastava, N., Gazzaneo, M.C., Murgas-Torrazza, R., Suryawan, A., Nguyen, H.V., El-Kadi, S.W., Fiorotto, M.L., Davis, T.A. 2010. Mechanical ventilation alone, and in the presence sepsis, induces peripheral skeletal muscle catabolism in neonatal pigs [abstract]. In: proceedings of the 2010 Pediatric Academic Societies Annual Conference, May 1-4, 2010, Vancouver, British Columbia, Canada. 2160.7. Interpretive Summary:
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. To determine the effects of mechanical ventilation and sepsis, alone or in combination, on protein synthesis and degradation in peripheral skeletal muscle. Neonatal pigs (n=5-6/group) were subjected to MV and infused with endotoxin (LPS, 0 and 10 micro g/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, which is involved in the activation of translation of mRNA into protein, by 70%. MV decreased eIF4G/4E association by 95% in the presence of LPS. The abundance of the E3 ligase, MURF-1, which is involved in proteosomal degradation, was increased 6- and 9-fold with MV and MV+ LPS respectively. In conclusion, 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.