title: Differential effects of octanoate and heptanoate on myocardial metabolism during extracorporeal membrane oxygenation in an infant swine model.
abstract: Nutritional energy support during extracorporeal membrane oxygenation (ECMO) should promote successful myocardial adaptation and eventual weaning from the ECMO circuit. Fatty acids (FAs) are a major myocardial energy source, and medium-chain FAs (MCFAs) are easily taken up by cell and mitochondria without membrane transporters. Odd-numbered MCFAs supply carbons to the citric acid cycle (CAC) via anaplerotic propionyl-CoA as well as acetyl-CoA, the predominant β-oxidation product for even-numbered MCFA. Theoretically, this anaplerotic pathway enhances carbon entry into the CAC, and provides superior energy state and preservation of protein synthesis. We tested this hypothesis in an immature swine model undergoing ECMO. Fifteen male Yorkshire pigs (26-45 days old) with 8-h ECMO received either normal saline, heptanoate (odd-numbered MCFA), or octanoate (even-numbered MCFA) at 2.3 μmol·kg body wt(-1)·min(-1) as MCFAs systemically during ECMO (n = 5/group). The 13-carbon ((13)C)-labeled substrates ([2-(13)C]lactate, [5,6,7-(13)C3]heptanoate, and [U-(13)C6]leucine) were systemically infused as metabolic markers for the final 60 min before left ventricular tissue extraction. Extracted tissues were analyzed for the (13)C-labeled and absolute concentrations of metabolites by nuclear magnetic resonance and gas chromatography-mass spectrometry. Octanoate produced markedly higher myocardial citrate concentration, and led to a higher [ATP]-to-[ADP] ratio compared with other groups. Unexpectedly, octanoate and heptanoate increased the flux of propionyl-CoA relative to acetyl-CoA into the CAC compared with control. MCFAs promoted increases in leucine oxidation, but were not associated with a difference in protein synthesis rate. In conclusion, octanoate provides energetic advantages to the heart over heptanoate.
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington;
authors.forename: Masaki
authors.initials: M
authors.lastname: Kajimoto
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington;
authors.forename: Dolena R
authors.initials: DR
authors.lastname: Ledee
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington; Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, Washington;
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Olson
authors.affiliation: Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratories, Richland, Washington; and.
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Isern
authors.affiliation: Department of Nutrition, Université de Montréal and Montreal Heart Institute, Montréal, Quebec, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Des Rosiers
authors.affiliation: Center for Developmental Therapeutics, Seattle Children's Research Institute, Seattle, Washington; Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, Washington; michael.portman@seattlechildrens.org.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Portman
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000378:metabolism / Q000494:pharmacology*; D002247:Carbon Isotopes; D019343:Citric Acid / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects*; D004734:Energy Metabolism; D015199:Extracorporeal Membrane Oxygenation; D008401:Gas Chromatography-Mass Spectrometry; D006321:Heart / Q000187:drug effects*; D006537:Heptanoates / Q000378:metabolism / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D034421:Sus scrofa; D013552:Swine
chemical_list: D000214:Acyl Coenzyme A; D002210:Caprylates; D002247:Carbon Isotopes; D006537:Heptanoates; D019343:Citric Acid; C009061:propionyl-coenzyme A; D000244:Adenosine Diphosphate; D000105:Acetyl Coenzyme A; D000255:Adenosine Triphosphate; D007930:Leucine; C031492:octanoic acid
keywords: cardiac metabolism; extracorporeal circulation; fatty acids; pediatrics