METABOLISM OF [3-C-13]PYRUVATE AND [3-C-13]PROPIONATE IN NORMAL AND ISCHEMIC RAT-HEART IN-VIVO - H-1-NMR AND C-13-NMR STUDIES

The oxidation of 3-C-13 pyruvate and 3-C-13 propionate was studied in vivo in infused rats. The infused 3-C-13 pyruvate was quickly converted to 3-C-13 lactate in the blood, and the 3-C-13 lactate formed was well metabolized in both normoxic and ischaemic hearts. Large differences (200-600%) in the C-13 enrichment of alanine (C-3) and acetyl-CoA (C-2) compared with lactate (C-3) were found in both normoxic and ischaemic hearts, suggesting that the extracellular 3-C-13 lactate preferentially entered a region of the cytoplasm which specifically transfers the labelled pyruvate (formed from 3-C-13 lactate) to the mitochondria. The highly enriched mitochondrial pyruvate gave high enrichment in alanine and acetyl-CoA, which was detected by H-1- and C-13-NMR spectroscopy. Ischaemia increased C-13 incorporation into the main cytoplasmic lactate pool and decreased C-13 incorporation into citric acid cycle intermediates, mainly decreasing the pyruvate anaplerosis. Isoprenaline-induced ischaemia of the heart caused only a slight decrease in pyruvate oxidation. In contrast to the decreased anaplerosis of pyruvate, the anaplerosis of propionate (and propionyl-carnitine) increased significantly in ischaemic hearts, which may contribute to the protective effect of propionyl-carnitine seen in ischaemia. In addition, we found that 3-C-13 propionate preferentially labelled aspartate C-3 in rat heart, suggesting incomplete randomization of label in the succinyl-CoA-malate span of the citric acid cycle. These data show that proton observed C-13 edited spectroscopic methods, i.e. heteronuclear spin-echo and the one-dimensional heteronuclear multiple quantum coherence sequence, can be successfully used to study heart metabolism in vivo.