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Title: Mechanical ventilation alone, and in the presence of sepsis, impair protein metabolism in the diaphragm of neonatal pigs

Author
item ORELLANA, RENAN - Children'S Nutrition Research Center (CNRC)
item SRIVASTAVA, NEERAJ - Children'S Nutrition Research Center (CNRC)
item GAZZANEO, MARIA - Children'S Nutrition Research Center (CNRC)
item MURGAS-TORRAZZA, ROBERTO - Children'S Nutrition Research Center (CNRC)
item SURYAWAN, AGUS - Children'S Nutrition Research Center (CNRC)
item NGUYEN, HANH - Children'S Nutrition Research Center (CNRC)
item EL-KADI, SAMER - Children'S Nutrition Research Center (CNRC)
item FIOROTTO, MARTA - Children'S Nutrition Research Center (CNRC)
item DAVIS, TERESA - Children'S Nutrition Research Center (CNRC)

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 of sepsis, impair protein metabolism in the diaphragm of neonatal pigs [abstract]. In: Proceedings of the 2010 Pediatric Academic Societies Annual Conference, May 1-4, 2010, Vancouver,British Columbia, Canada. 3716.172.

Interpretive Summary:

Technical Abstract: Mechanical ventilation (MV) impairs diaphragmatic function and diminishes the ability to wean from ventilatory support in adult humans. In normal neonatal pigs, animals that are highly anabolic, endotoxin (LPS) infusion induces sepsis, reduces peripheral skeletal muscle protein synthesis rates, but increases protein synthesis in the diaphragm. To determine whether MV and sepsis, alone or in combination, lead to protein catabolism in the diaphragm. Neonatal pigs (n=5-6/group) were subjected to MV and infused with LPS (0 and 10 micro g/kg(-1)/hr(-1)), as well as dextrose and a balanced amino acid mixture. After 9 hours, fractional protein synthesis rates and translation and degradation signals were determined in diaphragm muscle. Compared to controls, MV alone decreased protein synthesis in the diaphragm by 16%, and this effect was not further aggravated by the addition of LPS. MV alone and in the presence of LPS decreased translation of mRNA into protein by decreasing eIF4G/eIF4E association and eIF4G phosphorylation in similar proportion when compared to controls. MV alone increased the E3 ligase MURF-1 abundance by 240% and by 340% in the presence of LPS, indicating activation of proteosomal degradation. In conclusion, these findings suggest that MV induces diaphragmatic wasting due to both decreased protein synthesis and increased proteolysis, and that the presence of LPS-induced sepsis enhances the MV-associated induction of proteosomal degradation in the diaphragm.