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Abstract #0659

Detection of Sudden Changes in Cardiac Metabolism by Hyperpolarized 13C MRS

Chalermchai Khemtong1, Nicholas R. Carpenter1, Lloyd L. Lumata1, Matthew E. Merritt1, Karlos X. Moreno1, Zoltan Kovacs1, Craig R. Malloy1, A. Dean Sherry1, 2

1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States; 2Department of Chemistry, University of Texas at Dallas, Richardson, TX, United States

DNP hyperpolarization of 13C-enriched substrates now allows detection of real-time metabolism in isolated perfused organs and in tissues in vivo. Due to the highly improved NMR sensitivity achieved by dynamic nuclear polarization (DNP), metabolism of HP 13C-enriched pyruvate through the citric acid (TCA) cycle by NMR and MRI has been plausible. Here, we report a hyperpolarized 13C-MRS technique as a tool to detect sudden changes in cardiac metabolism in perfused hearts as a result of cardiac drug stimulation. In perfused rat hearts receiving hyperpolarized [1-13C]pyruvate, a rapid increase in the signal intensity of [1-13C]lactate occurs after stimulation of cardiac function by isoproterenol. This results in the appearance of a second apex in the 13C NMR spectrum of HP-lactate derived from HP-pyruvate. No changes were observed in the kinetic appearance of other metabolite resonances derived from HP-pyruvate. This unusual feature was later traced to a rapid increase in the pool size of lactate as a result of glycogenolysis and subsequent glycolysis stimulated by isoproterenol. These results demonstrate the feasibility of using HP 13C MRS as a tool to detect rapid changes in cardiac metabolism in response to exposure to cardiac drugs.