In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate

Sonal Josan, Jae Mo Park, Ralph Hurd, Yi Fen Yen, Adolf Pfefferbaum, Daniel Spielman, Dirk Mayer

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Hyperpolarized 13C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl-coenzyme A (acetyl-CoA). [1-13C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in 13C-bicarbonate production after dichloroacetate (DCA) administration. With [1-13C]pyruvate, the 13C label is released as 13CO2/13C-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 13C label into the TCA (tricarboxylic acid) cycle and measure [5-13C]glutamate as well as study changes in [1-13C]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 13C labeling of [5-13C]glutamate, and a considerable increase in [1-13C]acetylcarnitine and [1,3-13C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2-13C]lactate, [2-13C]alanine and [5-13C]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.

Original languageEnglish (US)
Pages (from-to)1680-1687
Number of pages8
JournalNMR in biomedicine
Volume26
Issue number12
DOIs
StatePublished - Dec 1 2013
Externally publishedYes

Fingerprint

Pyruvic Acid
Metabolism
Rats
Pyruvate Dehydrogenase Complex
Dobutamine
Glutamic Acid
Acetyl Coenzyme A
Acetylcarnitine
Citric Acid Cycle
Bicarbonates
Fluxes
Labeling
Labels
Metabolic Networks and Pathways
Workload
Alanine
Lactic Acid
Oxidation

Keywords

  • Dichloroacetate
  • Dobutamine
  • Dose
  • Heart
  • Hyperpolarized C
  • Metabolism
  • Pyruvate

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

Cite this

In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate. / Josan, Sonal; Park, Jae Mo; Hurd, Ralph; Yen, Yi Fen; Pfefferbaum, Adolf; Spielman, Daniel; Mayer, Dirk.

In: NMR in biomedicine, Vol. 26, No. 12, 01.12.2013, p. 1680-1687.

Research output: Contribution to journalArticle

Josan, Sonal ; Park, Jae Mo ; Hurd, Ralph ; Yen, Yi Fen ; Pfefferbaum, Adolf ; Spielman, Daniel ; Mayer, Dirk. / In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate. In: NMR in biomedicine. 2013 ; Vol. 26, No. 12. pp. 1680-1687.
@article{42bca29840494e2c8b686a1dd1074f10,
title = "In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate",
abstract = "Hyperpolarized 13C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl-coenzyme A (acetyl-CoA). [1-13C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in 13C-bicarbonate production after dichloroacetate (DCA) administration. With [1-13C]pyruvate, the 13C label is released as 13CO2/13C-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 13C label into the TCA (tricarboxylic acid) cycle and measure [5-13C]glutamate as well as study changes in [1-13C]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 13C labeling of [5-13C]glutamate, and a considerable increase in [1-13C]acetylcarnitine and [1,3-13C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2-13C]lactate, [2-13C]alanine and [5-13C]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.",
keywords = "Dichloroacetate, Dobutamine, Dose, Heart, Hyperpolarized C, Metabolism, Pyruvate",
author = "Sonal Josan and Park, {Jae Mo} and Ralph Hurd and Yen, {Yi Fen} and Adolf Pfefferbaum and Daniel Spielman and Dirk Mayer",
year = "2013",
month = "12",
day = "1",
doi = "10.1002/nbm.3003",
language = "English (US)",
volume = "26",
pages = "1680--1687",
journal = "NMR in Biomedicine",
issn = "0952-3480",
publisher = "John Wiley and Sons Ltd",
number = "12",

}

TY - JOUR

T1 - In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-13C] and [2-13C]pyruvate

AU - Josan, Sonal

AU - Park, Jae Mo

AU - Hurd, Ralph

AU - Yen, Yi Fen

AU - Pfefferbaum, Adolf

AU - Spielman, Daniel

AU - Mayer, Dirk

PY - 2013/12/1

Y1 - 2013/12/1

N2 - Hyperpolarized 13C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl-coenzyme A (acetyl-CoA). [1-13C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in 13C-bicarbonate production after dichloroacetate (DCA) administration. With [1-13C]pyruvate, the 13C label is released as 13CO2/13C-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 13C label into the TCA (tricarboxylic acid) cycle and measure [5-13C]glutamate as well as study changes in [1-13C]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 13C labeling of [5-13C]glutamate, and a considerable increase in [1-13C]acetylcarnitine and [1,3-13C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2-13C]lactate, [2-13C]alanine and [5-13C]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.

AB - Hyperpolarized 13C MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl-coenzyme A (acetyl-CoA). [1-13C]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in 13C-bicarbonate production after dichloroacetate (DCA) administration. With [1-13C]pyruvate, the 13C label is released as 13CO2/13C-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 13C label into the TCA (tricarboxylic acid) cycle and measure [5-13C]glutamate as well as study changes in [1-13C]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 13C labeling of [5-13C]glutamate, and a considerable increase in [1-13C]acetylcarnitine and [1,3-13C]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2-13C]lactate, [2-13C]alanine and [5-13C]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.

KW - Dichloroacetate

KW - Dobutamine

KW - Dose

KW - Heart

KW - Hyperpolarized C

KW - Metabolism

KW - Pyruvate

UR - http://www.scopus.com/inward/record.url?scp=84888050726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84888050726&partnerID=8YFLogxK

U2 - 10.1002/nbm.3003

DO - 10.1002/nbm.3003

M3 - Article

C2 - 23904148

AN - SCOPUS:84888050726

VL - 26

SP - 1680

EP - 1687

JO - NMR in Biomedicine

JF - NMR in Biomedicine

SN - 0952-3480

IS - 12

ER -