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

• Published in: NMR in biomedicine Vol. 26; no. 12; pp. 1680 - 1687
• Main Authors: Josan, Sonal, Park, Jae Mo, Hurd, Ralph, Yen, Yi-Fen, Pfefferbaum, Adolf, Spielman, Daniel, Mayer, Dirk
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.12.2013; Wiley Subscription Services, Inc
• Subjects: Animals; Bicarbonate; Carbon Isotopes; dichloroacetate; Dichloroacetic Acid - metabolism; dobutamine; Dobutamine - metabolism; dose; heart; hyperpolarized 13C; Magnetic Resonance Spectroscopy; Male; metabolism; Myocardium - metabolism; pyruvate; Pyruvic Acid - metabolism; Rats; Rats, Wistar; Time Factors; hyperpolarized 13C; dose; dichloroacetate; dobutamine; metabolism; pyruvate; heart
• ISSN: 0952-3480; 1099-1492
• DOI: 10.1002/nbm.3003

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. Copyright © 2013 John Wiley & Sons, Ltd. This work uses hyperpolarized [2‐13C]pyruvate to investigate changes in the metabolic fate of acetyl‐CoA in response to DCA‐induced increased PDH flux, and increased cardiac workload with dobutamine. The change in glutamate with dobutamine was observed to depend on pyruvate dose. The lower DCA‐induced increase in glutamate compared with bicarbonate from [1‐13C]pyruvate provides information about the relationship between PDH‐mediated oxidation of pyruvate and its subsequent incorporation into the TCA cycle compared with other metabolic pathways.