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

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.