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Mechanical ventilation and sepsis induce skeletal muscle catabolism in neonatal pigs
Author(s) -
Orellana Renán A,
Srivastava Neeraj,
Gazzaneo María C.,
Torrazza Roberto Murgas,
Suryawan Agus,
ElKadi Samer W.,
Fiorotto Marta L.,
Davis Teresa A.,
Nguyen Hanh V.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.740.34
Subject(s) - skeletal muscle , sepsis , catabolism , wasting , medicine , protein degradation , endocrinology , protein catabolism , mechanical ventilation , chemistry , biology , biochemistry , metabolism , amino acid
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 μg•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. NIH AR51563, NIH AR44474, and USDA 6250‐51000‐040 Grant Funding Source: NIH AR44474, and USDA 6250‐51000‐040