Mechanical Circulatory Unloading Promotes Proteins Synthesis and Maintains Leucine Oxidation

Abstract

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 13C6, 15N L‐leucine alone or with 2‐13C 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 13C‐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.ConclusionsMechanical 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.