Spatial heterogeneity of energy turnover in the heart

Local myocardial blood flow varies substantially in spite of a;ather homoge neous morphology. To further elucidate this paradox, the spatial heterogene ity of tricarboxylic acid cycle turnover (J(TCA), mu mol min(-1) g(-1)) and coronary flow was assessed at a high spatial resolution (6x6x6 mm(3)) in t he open chest dog. Local flow differed more than 2.5-fold between individua l samples in each heart (n=7). Out of 1500 myocardial samples, 1/10 receive d less than 60% and another 1/10 more than 138% of the normalized mean. In low- and high-flow samples, pyruvate uptake and metabolism were analyzed by C-13 NMR spectroscopy. Following [3-C-13]pyruvate infusion (2 mM, 12 min), glutamate [4-C-13]/[3-13C] was significantly greater in low-flow (2.21+/-0 .75, 40 samples) than in high-flow (1.6+/-0.49, 39 samples) areas. This sug gests that there are major differences in J(TCA) Glutamate, citrate and lac tate content positively correlated with flow. Anaplerotic pathways contribu ted a fraction similar to J(TCA) in low- and high flow areas, as demonstrat ed by isotopomer analysis after 60 min of [3-C-13]pyruvate application. Mat hematical model analysis of NMR data and relevant pool sizes revealed that J(TCA) and thus myocardial oxygen consumption (MVO2) in high-flow areas exc eed values in low-flow areas at least threefold, Thus low and high metaboli c states normally coexist within the well perfused heart, suggesting that t here is considerable spatial heterogeneity of cardiac energy generation and work.