Inhibition of carbohydrate oxidation during the first minute of reperfusion after brief ischemia: NMR detection of hyperpolarized 13CO 2 and H13CO3-

Abstract

Isolated rat hearts were studied by 31P NMR and 13C NMR. Hyperpolarized [1-13C]pyruvate was supplied to control normoxic hearts and production of [1-13C]lactate, [1-13C]alanine, 13CO2 and H13CO3- was monitored with 1-s temporal resolution. Hearts were also subjected to 10 min of global ischemia 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, [1-13C]alanine and [1-13C]lactate appeared rapidly, demonstrating metabolism of pyruvate through two enzymes largely confined to the cytosol, alanine aminotransferase, and lactate dehydrogenase. 13CO2 and H13CO3- were not detected. Late after ischemia and reperfusion, the products of pyruvate dehydrogenase, 13CO 2 and H13CO3- 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. © 2008 Wiley-Liss, Inc.