title: Myocardial reloading after extracorporeal membrane oxygenation alters substrate metabolism while promoting protein synthesis.
abstract: BACKGROUND
  Extracorporeal membrane oxygenation (ECMO) unloads the heart, providing a bridge to recovery in children after myocardial stunning. ECMO also induces stress which can adversely affect the ability to reload or wean the heart from the circuit. Metabolic impairments induced by altered loading and/or stress conditions may impact weaning. However, cardiac substrate and amino acid requirements upon weaning are unknown. We assessed the hypothesis that ventricular reloading with ECMO modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis.
  
  
  RESULTS
  Sixteen immature piglets (7.8 to 15.6 kg) were separated into 2 groups based on ventricular loading status: 8-hour ECMO (UNLOAD) and postwean from ECMO (RELOAD). We infused into the coronary artery [2-(13)C]-pyruvate as an oxidative substrate and [(13)C6]-L-leucine as an indicator for amino acid oxidation and protein synthesis. Upon RELOAD, each functional parameter, which were decreased substantially by ECMO, recovered to near-baseline level with the exclusion of minimum dP/dt. Accordingly, myocardial oxygen consumption was also increased, indicating that overall mitochondrial metabolism was reestablished. At the metabolic level, when compared to UNLOAD, RELOAD altered the contribution of various substrates/pathways to tissue pyruvate formation, favoring exogenous pyruvate versus glycolysis, and acetyl-CoA formation, shifting away from pyruvate decarboxylation to endogenous substrate, presumably fatty acids. Furthermore, there was also a significant increase of tissue concentrations for all CAC intermediates (≈80%), suggesting enhanced anaplerosis, and of fractional protein synthesis rates (>70%).
  
  
  CONCLUSIONS
  RELOAD alters both cytosolic and mitochondrial energy substrate metabolism, while favoring leucine incorporation into protein synthesis rather than oxidation in the CAC. Improved understanding of factors governing these metabolic perturbations may serve as a basis for interventions and thereby improve success rate from weaning from ECMO.
authors: Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, WA.
authors: Masaki
authors: M
authors: Kajimoto
authors: Colleen M
authors: CM
authors: O'Kelly Priddy
authors: Dolena R
authors: DR
authors: Ledee
authors: Chun
authors: C
authors: Xu
authors: Nancy
authors: N
authors: Isern
authors: Aaron K
authors: AK
authors: Olson
authors: Christine
authors: C
authors: Des Rosiers
authors: Michael A
authors: MA
authors: Portman
mesh_terms: D000367:Age Factors; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects; D008401:Gas Chromatography-Mass Spectrometry; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D020127:Recovery of Function; D013552:Swine; D013997:Time Factors; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
chemical_list: D000596:Amino Acids; D009124:Muscle Proteins
keywords: amino acids; congenital heart disease; extracorporeal circulation; metabolism; pediatrics
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