Propionate Increase Hyperpolarized H13CO3- Signal in Perfused Mouse Hearts



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BACKGROUND: As early as 2008, MR imaging of [1-13C]pyruvate and its metabolites, including bicarbonate, in post-ischemic pig hearts was reported (1). Since the method does not use ionizing radiation, there is widespread interest in applications in other fields including oncology (2). In the heart, pyruvate is oxidized to acetyl-CoA and CO2. Oxidation of hyperpolarized (HP) [1-13C]pyruvate to HP [13C]bicarbonate is reduced in injured myocardium, and the presence of preserved flux through pyruvate dehydrogenase (PDH) may identify viable myocardium (1). However, oxidation of alternative substrates normally present in the blood also reduces the appearance of HP [13C]bicarbonate even in healthy myocardium (3). Propionate, a short-chain three-carbon fatty acid normally present in the blood, is known to activate PDH, and it is under study as a nutritional therapy for heart failure (4). The efficacy of propionate for restoring PDH flux in hearts supplied with high concentrations of glucose and fatty acids was studied using 13C NMR isotopomer analysis paired with experiments using HP [1-13C]pyruvate. 13C NMR is a standard method for measuring fluxes in metabolic pathways. METHODS AND RESULTS: Hearts excised from fed C57/bl6 mice were perfused in Langendorff mode using a mixture of acetate (2 mM), glucose (8.25 mM), and with and without propionate (2 mM). O2 consumption was not changed for the two different perfusion conditions. Isotopomer analysis of extracts of the freeze-clamped hearts indicated that carboxylation of propionate was very active, as expected, and glucose oxidation was minimal. For HP experiments, the perfused heart was located inside a 10 mm cryogenically-cooled probe paired with a 14.1 Tesla nuclear magnetic resonance spectrometer. After addition of hyperpolarized pyruvate, NMR signals from lactate, alanine, bicarbonate, CO2, aspartate, malate, acetyl-carnitine, and glutamate were detected in real time and in a highly reproducible manner. The presence of propionate increased appearance of HP [13C]bicarbonate 37-fold. This is the first application of hyperpolarization with detection using a cryogenically-cooled probe. CONCLUSION: In the presence of a high concentration of a competing substrate, propionate stimulates PDH flux in perfused mouse hearts as measured by the appearance of hyperpolarized [13C]bicarbonate from metabolism of hyperpolarized [1-13C]pyruvate. REFERENCES

  1. Golman K, Petersson JS, Magnusson P, Johansson E, Akeson P, Chai CM, Hansson G, Månsson S. Cardiac metabolism measured noninvasively by hyperpolarized 13C MRI. Magn Reson Med. 2008; 59: 1005-13. PMID: 18429038
  2. Harrison CE, DeBerardinis RJ, Jindal AK, Yang C, Sherry AD, Malloy CR. Analysis of mitochondrial metabolism in cancer cells by combining hyperpolarization and isotopomer analysis. Proc Int Soc Magn Reson Med 2010;18:569.
  3. Moreno KX, Sabelhaus SM, Merritt ME, Sherry AD, Malloy CR. Competition of Pyruvate with Physiological Substrates for Oxidation by the Heart: Implications for Studies with Hyperpolarized [1-13C]Pyruvate. Am J Physiol Heart Circ Physiol. 2010; 298: H1556 - 64. PMID: 20207817
  4. Lango R, Smoleski RT, Rogowski J, Siebert J, Wujtewicz M, S?omi?ska EM, Lysiak-Szyd?owska W, Yacoub MH. Propionyl-L-carnitine improves hemodynamics and metabolic markers of cardiac perfusion during coronary surgery in diabetic patients. Cardiovasc Drugs Ther. 2005; 19: 267-75. PMID: 16187006

General Notes

The 52nd Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, February 4, 2014, 3-6 p.m., D1.502)

Table of Contents


Basic Research and Disease Models, Acetates, Myocardium, Propionates, Pyruvic Acid


Purmal, C., Malloy, C. R., Sherry, A. D., & Merritt, M. E. (2014, February 4). Propionate increase hyperpolarized H13CO3- signal in perfused mouse hearts. Poster session presented at the 52nd Annual Medical Student Research Forum, Dallas, TX. Retrieved from

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