title: Myocardial oxidative metabolism and protein synthesis during mechanical circulatory support by extracorporeal membrane oxygenation.
abstract: Extracorporeal membrane oxygenation (ECMO) provides essential mechanical circulatory support necessary for survival in infants and children with acute cardiac decompensation. However, ECMO also causes metabolic disturbances, which contribute to total body wasting and protein loss. Cardiac stunning can also occur, which prevents ECMO weaning, and contributes to high mortality. The heart may specifically undergo metabolic impairments, which influence functional recovery. We tested the hypothesis that ECMO alters oxidative metabolism and protein synthesis. We focused on the amino acid leucine and integration with myocardial protein synthesis. We used a translational immature swine model in which we assessed in heart 1) the fractional contribution of leucine (FcLeucine) and pyruvate to mitochondrial acetyl-CoA formation by nuclear magnetic resonance and 2) global protein fractional synthesis (FSR) by gas chromatography-mass spectrometry. Immature mixed breed Yorkshire male piglets (n = 22) were divided into four groups based on loading status (8 h of normal circulation or ECMO) and intracoronary infusion [(13)C(6),(15)N]-L-leucine (3.7 mM) alone or with [2-(13)C]-pyruvate (7.4 mM). ECMO decreased pulse pressure and correspondingly lowered myocardial oxygen consumption (∼40%, n = 5), indicating decreased overall mitochondrial oxidative metabolism. However, FcLeucine was maintained and myocardial protein FSR was marginally increased. Pyruvate addition decreased tissue leucine enrichment, FcLeucine, and Fc for endogenous substrates as well as protein FSR. The heart under ECMO shows reduced oxidative metabolism of substrates, including amino acids, while maintaining 1) metabolic flexibility indicated by ability to respond to pyruvate and 2) a normal or increased capacity for global protein synthesis.
authors.affiliation: Department of Surgery, University of Washington, Seattle, Washington, USA.
authors.forename: Colleen M O'Kelly
authors.initials: CM
authors.lastname: Priddy
authors.forename: Masaki
authors.initials: M
authors.lastname: Kajimoto
authors.forename: Dolena R
authors.initials: DR
authors.lastname: Ledee
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bouchard
authors.forename: Nancy
authors.initials: N
authors.lastname: Isern
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Olson
authors.forename: Christine
authors.initials: C
authors.lastname: Des Rosiers
authors.forename: Michael A
authors.initials: MA
authors.lastname: Portman
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002952:Citric Acid Cycle / Q000187:drug effects; D015199:Extracorporeal Membrane Oxygenation; D008401:Gas Chromatography-Mass Spectrometry; D006321:Heart / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006454:Hemoglobins / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007930:Leucine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis / Q000502:physiology*; D019289:Pyruvic Acid / Q000378:metabolism; D013552:Swine
chemical_list: D006454:Hemoglobins; D015850:Interleukin-6; D000105:Acetyl Coenzyme A; D019289:Pyruvic Acid; D007930:Leucine