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

Purpose The diseased myocardium lacks metabolic flexibility and responds to stimuli differently compared with healthy hearts. Here, we report the use of hyperpolarized 13 C NMR spectroscopy to detect sudden changes in cardiac metabolism in isolated, perfused rat hearts in response to adrenergic stimulation. Methods Metabolism of hyperpolarized [1‐ 13 C]pyruvate was investigated in perfused rat hearts. The hearts were stimulated in situ by isoproterenol shortly after the administration of hyperpolarized [1‐ 13 C]pyruvate. The hyperpolarized 13 C NMR results were corroborated with 1 H NMR spectroscopy of tissue extracts. Results Addition of isoproterenol to hearts after equilibration of hyperpolarized [1‐ 13 C]pyruvate into the existing lactate pool resulted in a sudden, rapid increase in hyperpolarized [1‐ 13 C]lactate signal within seconds after exposure to drug. The hyperpolarized H 13 CO 3 − and hyperpolarized [1‐ 13 C]alanine signals were not affected by the isoproterenol‐induced elevated cardiac workload. Separate experiments confirmed that the new hyperpolarized [1‐ 13 C]lactate signal that arises after stimulation by isoproterenol reflects a sudden increase in total tissue lactate derived from glycogen. Conclusion These results suggest that hyperpolarized pyruvate and 13 C MRS may be useful for detecting abnormal glycogen metabolism in intact tissues. Magn Reson Med 74:312–319, 2015. © 2014 Wiley Periodicals, Inc.