title: In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate.
abstract: Hyperpolarized (13)C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl-coenzyme A (acetyl-CoA). [1-(13)C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in (13)C-bicarbonate production after dichloroacetate (DCA) administration. With [1-(13)C]pyruvate, the (13)C label is released as (13 CO2 /(13)C-bicarbonate, and, hence, does not allow us to follow the fate of acetyl-CoA. Pyruvate labeled in the C2 position has been used to track the (13)C label into the TCA (tricarboxylic acid) cycle and measure [5-(13)C]glutamate as well as study changes in [1-(13)C]acetylcarnitine with DCA and dobutamine. This work investigates changes in the metabolic fate of acetyl-CoA in response to metabolic interventions of DCA-induced increased PDC flux in the fed and fasted state, and increased cardiac workload with dobutamine in vivo in rat heart at two different pyruvate doses. DCA led to a modest increase in the (13)C labeling of [5-(13)C]glutamate, and a considerable increase in [1-(13)C]acetylcarnitine and [1,3-(13)C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2-(13)C]lactate, [2-(13)C]alanine and [5-(13)C]glutamate. The change in glutamate with dobutamine was observed using a high pyruvate dose but not with a low dose. The relative changes in the different metabolic products provide information about the relationship between PDC-mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways. Using a high dose of pyruvate may provide an improved ability to observe changes in glutamate.
authors.affiliation: SRI International, Neuroscience Program, Menlo Park, CA, USA; Stanford University, Department of Radiology, Lucas MRI Center, Stanford, CA, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Josan
authors.forename: Jae Mo
authors.initials: JM
authors.lastname: Park
authors.forename: Ralph
authors.initials: R
authors.lastname: Hurd
authors.forename: Yi-Fen
authors.initials: YF
authors.lastname: Yen
authors.forename: Adolf
authors.initials: A
authors.lastname: Pfefferbaum
authors.forename: Daniel
authors.initials: D
authors.lastname: Spielman
authors.forename: Dirk
authors.initials: D
authors.lastname: Mayer
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D003999:Dichloroacetic Acid / Q000378:metabolism; D004280:Dobutamine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D004280:Dobutamine; D019289:Pyruvic Acid; D003999:Dichloroacetic Acid
keywords: dichloroacetate; dobutamine; dose; heart; hyperpolarized 13C; metabolism; pyruvate
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