Inhibition of Carbohydrate Oxidation During the First Minute of Reperfusion After Brief Ischemia: NMR Detection of Hyperpolarized 13CO2 and H13CO3-

Isolated rat hearts were studied by P-31 NMR and C-13 NMR. Hyperpolarized [1-C]pyruvate was supplied to control normoxic hearts and production of [1-13C]lactate, [1-13C]alanine, (CO2)-C-13 and (HCO3-)-C-13 was monitored with 1-s temporal resolution. Hearts were also subjected to 10 min of global ischernia followed by reperfusion. Developed pressure, heart rate, oxygen consumption, [ATP], [phosphocreatine], and pH recovered within 3 min after the ischemic period. During the first 90 s of reperfusion, [1 -C-13]alanine and [1 -C-13]lactate appeared rapidly, demonstrating metabolism of pyruvate through two enzymes largely confined to the cytosol, alanine aminotransferase, and lactate dehydrogenase. (CO2)-C-13 and (HCO3-)-C-13 were not detected. Late after ischernia and reperfusion, the products of pyruvate dehydrogenase, (CO2)-C-13 and (HCO3)-C-13- were easily detected. Using this multinuclear NMR approach, we established that during the first 90 s of reperfusion PDH flux is essentially zero and recovers within 20 min in reversibly-injured myocardium. Magn Reson Med 60:1029-1036, 2008. (C) 2008 Wiley-Liss, Inc.