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-13pyruvate and 3-C-13propionate was studied i n vivo in infused rats. The infused 3-C-13pyruvate was quickly conve rted to 3-C-13lactate in the blood, and the 3-C-13lactate formed w as well metabolized in both normoxic and ischaemic hearts. Large diffe rences (200-600%) in the C-13 enrichment of alanine (C-3) and acetyl-C oA (C-2) compared with lactate (C-3) were found in both normoxic and i schaemic hearts, suggesting that the extracellular 3-C-13lactate pre ferentially entered a region of the cytoplasm which specifically trans fers the labelled pyruvate (formed from 3-C-13lactate) to the mitoch ondria. The highly enriched mitochondrial pyruvate gave high enrichmen t in alanine and acetyl-CoA, which was detected by H-1- and C-13-NMR s pectroscopy. Ischaemia increased C-13 incorporation into the main cyto plasmic lactate pool and decreased C-13 incorporation into citric acid cycle intermediates, mainly decreasing the pyruvate anaplerosis. Isop renaline-induced ischaemia of the heart caused only a slight decrease in pyruvate oxidation. In contrast to the decreased anaplerosis of pyr uvate, the anaplerosis of propionate (and propionyl-carnitine) increas ed significantly in ischaemic hearts, which may contribute to the prot ective effect of propionyl-carnitine seen in ischaemia. In addition, w e found that 3-C-13propionate preferentially labelled aspartate C-3 in rat heart, suggesting incomplete randomization of label in the succ inyl-CoA-malate span of the citric acid cycle. These data show that pr oton observed C-13 edited spectroscopic methods, i.e. heteronuclear sp in-echo and the one-dimensional heteronuclear multiple quantum coheren ce sequence, can be successfully used to study heart metabolism in viv o.