Non-invasive measurements of myocardial carbon metabolism using in vivo 13C NMR spectroscopy

Despite their prime role in maintaining contractile performance, myocardial substrate uptake, substrate preference and metabolism are difficult to assess non-invasively. The objective of the present work was to extend the scope of cardiac 13C nuclear magnetic resonance (NMR) spectroscopy to the in vivo situation ('closed-chest model') and to quantitatively appraise myocardial metabolism in vivo. For this purpose, overnight-fasted Sprague-Dawley rats received intravenous infusions of non-radioactive 13C-labeled glucose, 3-hydroxybutyrate, and acetate as markers for glycolysis, metabolism of ketone bodies and direct incorporation into tricarboxylic acid (TCA) cycle, respectively. In vivo 13C NMR spectra (at 7 T) were acquired from the myocardium with a time resolution of 6 min. At the end of the infusion experiments, tissue extracts were prepared and further analyzed by high-resolution 13C NMR spectroscopy in order to corroborate the findings obtained in vivo. Accordingly, 3-hydroxybutyrate and acetate were rapidly extracted by the myocardium and supplied 42 +/- 6 and 53 +/- 9% of the acetyl-CoA for TCA cycle operation, whereas glucose, although also well extracted, did not contribute to myocardial oxidative metabolism. Myocardial TCA cycle turnover (V(TCA)) in vivo was estimated at 1.34 +/- 0.07 micromol/min/g wet weight, myocardial oxygen consumption (MVO2) at 2.95 +/- 0.16 micromol/min/g wet weight, exchange rate between alpha-ketoglutarate and glutamate (V(x)) at 1.22 +/- 0.08 micromol/min/g wet weight and rate of glutamine synthesis (V(gln)) at 0.14 +/- 0.02 micromol/min/g wet weight. The substantial synthesis of myocardial glutamine is in contrast to experiments with isolated and saline perfused hearts. In conclusion, it is demonstrated that 13C NMR spectroscopy of the heart in intact rats is feasible and provides new quantitative insight into myocardial substrate uptake, preference and metabolism in vivo.