Hyperpolarized 13C NMR detects rapid drug-induced changes in cardiac metabolism

PurposeThe diseased myocardium lacks metabolic flexibility and responds to stimuli differently compared with healthy hearts. Here, we report the use of hyperpolarized C-13 NMR spectroscopy to detect sudden changes in cardiac metabolism in isolated, perfused rat hearts in response to adrenergic stimulation. MethodsMetabolism of hyperpolarized [1-C-13]pyruvate was investigated in perfused rat hearts. The hearts were stimulated in situ by isoproterenol shortly after the administration of hyperpolarized [1-C-13]pyruvate. The hyperpolarized C-13 NMR results were corroborated with H-1 NMR spectroscopy of tissue extracts. ResultsAddition of isoproterenol to hearts after equilibration of hyperpolarized [1-C-13]pyruvate into the existing lactate pool resulted in a sudden, rapid increase in hyperpolarized [1-C-13]lactate signal within seconds after exposure to drug. The hyperpolarized (HCO3-)-C-13 and hyperpolarized [1-C-13]alanine signals were not affected by the isoproterenol-induced elevated cardiac workload. Separate experiments confirmed that the new hyperpolarized [1-C-13]lactate signal that arises after stimulation by isoproterenol reflects a sudden increase in total tissue lactate derived from glycogen. ConclusionThese results suggest that hyperpolarized pyruvate and C-13 MRS may be useful for detecting abnormal glycogen metabolism in intact tissues. Magn Reson Med 74:312-319, 2015. (c) 2014 Wiley Periodicals, Inc.