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Mechanical Circulatory Unloading Promotes Proteins Synthesis and Maintains Leucine Oxidation
Author(s) -
Kajimoto Masaki,
O'Kelly Priddy Colleen M.,
Ledee Dolena R.,
Bouchard Bertrand,
Isern Nancy,
Olson Aaron K.,
Des Rosiers Christine,
Portman Michael A.
Publication year - 2012
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.26.1_supplement.1127.1
Subject(s) - extracorporeal membrane oxygenation , leucine , phosphorylation , protein biosynthesis , amino acid , chemistry , circulatory system , citric acid cycle , citric acid , medicine , biochemistry , metabolism
Mechanical ventricular unloading by arterial‐venous extracorporeal membrane oxygenation (ECMO) serves as a bridge to recovery in infants with severe acute heart failure. The influence of mechanical circulatory support on protein synthesis and degradation is unknown. We tested the hypothesis: ECMO induces reductions in myocardial protein synthesis and promotes increased amino acid oxidation. Anesthetized immature swine (n=20) received intracoronary infusion of 13 C 6 , 15 N L‐leucine alone or with 2‐ 13 C pyruvate after 8 hours of loading (LOAD) or ECMO. Leucine incorporation into protein and contribution to the citric acid cycle (CAC) relative to pyruvate was determined using 13 C‐magnetic resonance spectroscopy and GCMS. ECMO increased the protein fractional synthesis rate (0.91%±0.04% vs. 0.63%±0.10%, p<0.06), but did not alter leucine oxidation relative to pyruvate. ECMO also increased mTOR phosphorylation (by immunoblot) and decreased eukaryotic‐Elongation factor‐2 phosphorylation. Conclusions Mechanical unloading in the form of ECMO enhances protein synthesis without reducing amino acid contribution of acetyl‐CoA to the CAC. The protein synthesis occurs with activation of the mTOR pathway. These data suggest that atrophy induced by clinical mechanical circulatory support and ventricular unloading is caused by accelerated protein degradation.