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

Hyperpolarized C-13 MRS allows the in vivo assessment of pyruvate dehydrogenase complex (PDC) flux, which converts pyruvate to acetyl-coenzyme A (acetyl-CoA). [1-C-13]pyruvate has been used to measure changes in cardiac PDC flux, with demonstrated increase in C-13-bicarbonate production after dichloroacetate (DCA) administration. With [1-C-13]pyruvate, the C-13 label is released as (CO2)-C-13/C-13-bicarbonate, and, hence, does not allow us to follow the fate of acetyl-CoA. Pyruvate labeled in the C-2 position has been used to track the C-13 label into the TCA (tricarboxylic acid) cycle and measure [5-C-13]glutamate as well as study changes in [1-C-13]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 C-13 labeling of [5-C-13]glutamate, and a considerable increase in [1-C-13]acetylcarnitine and [1,3-C-13]acetoacetate peaks. Dobutamine resulted in an increased labeling of [2-C-13]lactate, [2-C-13]alanine and [5-C-13]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 (c) 2013 John Wiley & Sons, Ltd.