DYNAMIC C-13 NMR ANALYSIS OF PYRUVATE AND LACTATE OXIDATION IN THE IN-VIVO CANINE MYOCARDIUM - EVIDENCE OF REDUCED UTILIZATION WITH INCREASED WORK

In this work, substrate selection was monitored in the left ventricle of the canine myocardium by following pyruvate and lactate oxidation u nder in vivo conditions at basal and elevated workloads, These studies were conducted in the open chest model using dynamic C-13 NMR techniq ues in the presence and absence of dichloroacetic acid (DCA), a well-k nown activator of pyruvate dehydrogenase (PDH), Following the infusion of (3-C-13) pyruvate or (3-C-13) lactate into the left anterior desce nding artery, highly variable C-13 enrichments of glutamate, alanine, aspartate, and citrate were noted under low (RPP <14,500 mmHg/min), in termediate (RPP = 15,000-25,000 mmHg/min), and high (RPP > 25,500 mmHg /min) rate pressure products (RPP), At low workloads, the myocardium t ypically oxidized the infused (3-C-13) pyruvate or (3-C-13) lactate an d incorporated the labeled carbon into the glutamate pool as expected. However, in a few notable instances (n = 3), C-13-enriched pyruvate a nd lactate were unable to label the glutamate pool under in vivo condi tions even at the lowest RPPs, indicating a lack of selection for thes e substrates by the tricarboxylic acid (TCA) cycle, Nonetheless, the l evels of glutamate C4 enrichment observed at low workloads could usual ly be enhanced by infusion of DCA, Importantly, C-13 NMR extract analy sis revealed that (3-C-13) pyruvate or (3-C-13) lactate labeling of th e glutamate pool was reduced (<20%) at high workloads in spite of incr eased DCA concentrations.