Abstract 16606: Myocardial Reloading after Extracorporeal Membrane Oxygenation Promotes Protein Synthesis and Alters Flux Through the Citric Acid Cycle
Background: Extracorporeal membrane oxygenation (ECMO) unloads the heart providing a bridge to recovery in children after myocardial stunning. Mortality after ECMO remains high. Cardiac substrate and amino acid requirements upon weaning are unknown and may impact recovery. Previously we reported ECMO modestly increases protein synthesis. We assessed the hypothesis that ventricular reloading modulates both substrate entry into the citric acid cycle (CAC) and myocardial protein synthesis.
Methods and Results: Nineteen immature piglets (7.8-15.6 kg) were separated into 3 groups based on ventricular loading status: normal circulation (LOAD), 8 hours of ECMO (UNLOAD) and post-wean (1hour) from ECMO (RELOAD). Myocardial oxygen consumption was reduced by UNLOAD and was increased more than baseline by RELOAD. [13C6,15N]-L-leucine, as a tracer of protein synthesis and amino acid oxidation, was infused into coronary artery with [2-13C]-pyruvate as an oxidative control. 13C-labeling data from gas chromatography/mass spectrometry and NMR demontrate that compared to LOAD and UNLOAD, which had similar effects, RELOAD resulted in the following metabolic changes: (i) substantially (p < 0.01) increased enrichment for (a) intracellular pyruvate, and free leucine, suggesting a greater contribution from their extracellular precursor, as well as (b) that of lactate and of all CAC intermediates, (ii) maintained the fractional acetyl-CoA contribution (FC) from leucine but decreased that of pyruvate, and (iii) significantly increased cardiac fractional protein synthesis rates by >100% over LOAD, and >75% over UNLOAD.
Conclusions: RELOAD after ECMO perturbs substrate flux and protein synthesis, possibly impacting the heart’s ability to sustain contractile function. Cardiac energy requirements surpass oxidative capacity and stimulate glycolysis, shown by increased flux to lactate. The data support overall amino acid incorporation into protein rather than to the CAC for oxidation and ATP generation. Elevated energy requirements can be required to support the increased protein turnover. These perturbations may serve as therapeutic targets to improve contractile function after ECMO.
- Extracorporeal circulation
- Pediatric cardiac intensive care
- Cardiac metabolism
- Ventricular remodeling
- Magnetic resonance spectroscopy
- © 2012 by American Heart Association, Inc.