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.