ARS | Publication request: Mechanical ventilation and sepsis impair protein metabolism in the diaphragm of 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
Repository URL: http://org/cgi/content/meeting_abstract/24/1_MeetingAbstracts/740.35?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=suryawan&searchid=1&FIRSTINDEX=0&volume=24&issue=1_MeetingAbstracts&resourcetype=HWCIT
Citation: Srivastava, N., Gazzaneo, M.C., Murgas-Torrazza, R., Suryawan, A., Nguyen, H.V., El-Kadi, S.W., Fiorotto, M.L., Davis, T.A., Orellana R.A. 2010. Mechanical ventilation and sepsis impair protein metabolism in the diaphragm of neonatal pigs [abstract]. Federation of American Societies for Experimental Biology Conference, Session: Protein and amino acid metabolism, April 24-28, 2010, Anaheim, California. 24:740.35.

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 lead to protein catabolism in the diaphragm, neonatal pigs (n=5–6/group) were subjected to MV and infused with LPS (0 and 10 ug/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 percent, and this effect was not further aggravated by the addition of LPS. MV alone and in the presence of LPS decreased eIF4G/eIF4E association and eIF4G phosphorylation in similar proportion when compared to controls. MV alone increased MURF-1 abundance by 240 percent and by 340 percent in the presence of LPS. These findings suggest that MV induces diaphragmatic wasting due to both decreased protein synthesis and increased proteolysis, and the presence of sepsis enhances the MV-associated induction of proteosomal degradation.