Josan, S., Park, J. M., Hurd, R., Yen, Y.-F., Pfefferbaum, A., Spielman, D., & Mayer, D. (2013). In vivo investigation of cardiac metabolism in the rat using MRS of hyperpolarized [1-C-13] and [2-C-13]pyruvate. NMR in Biomedicine, 26(12), 1680-1687.
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.