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Spatial heterogeneity of energy turnover in the heart
U K Decking1, S Skwirba, M F Zimmermann
1Dept. of Physiology, Heinrich-Heine-University Düsseldorf, Germany. decking@uni-duesseldorf.de
Insights
Local blood flow in the heart varies significantly, impacting energy production. This study reveals substantial spatial heterogeneity in cardiac energy generation and work, with high-flow areas showing at least threefold greater myocardial oxygen consumption than low-flow areas.
Area of Science:
- Cardiovascular Physiology
- Metabolic Imaging
- Cardiac Energetics
Background:
- Myocardial blood flow exhibits significant spatial heterogeneity despite uniform cardiac morphology.
- Understanding this paradox is crucial for comprehending cardiac function and energy metabolism.
Purpose of the Study:
- To investigate the spatial heterogeneity of tricarboxylic acid cycle turnover (J(TCA)) and coronary flow in the canine heart.
- To correlate local metabolic activity with myocardial blood flow at high spatial resolution.
Main Methods:
- High-resolution assessment of J(TCA) and coronary flow in open-chest dogs (6x6x6 mm3 voxels).
- 13C Nuclear Magnetic Resonance (NMR) spectroscopy following [3-13C]pyruvate infusion to analyze pyruvate uptake and metabolism.
- Isotopomer analysis and mathematical modeling of NMR data to determine metabolic rates and pool sizes.
Main Results:
- Local coronary flow varied more than 2.5-fold between samples.
- Glutamate [4-13C]/[3-13C] ratios indicated significantly different J(TCA) between low-flow and high-flow areas.
- Glutamate, citrate, and lactate content positively correlated with flow; J(TCA) and myocardial oxygen consumption (MVO2) were at least threefold higher in high-flow areas.
Conclusions:
- Significant spatial heterogeneity exists in cardiac energy generation and work within the heart.
- Low and high metabolic states coexist normally within the same well-perfused heart.
- Differences in J(TCA) and MVO2 contribute to the observed spatial metabolic variations.
Abstract:
Local myocardial blood flow varies substantially in spite of a rather homogeneous morphology. To further elucidate this paradox, the spatial heterogeneity of tricarboxylic acid cycle turnover (J(TCA), micromol min(-1) g(-1)) and coronary flow was assessed at a high spatial resolution (6x6x6 mm3) in the open chest dog. Local flow differed more than 2.5-fold between individual samples in each heart (n=7). Out of 1,500 myocardial samples, 1/10 received 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 13C NMR spectroscopy. Following [3-13C]pyruvate infusion (2 mM, 12 min), glutamate [4-13C]/[3-13C] was significantly greater in low-flow (2.21+/-0.75, 40 samples) than in high-flow (1.64+/-0.49, 39 samples) areas. This suggests that there are major differences in J(TCA). Glutamate, citrate and lactate content positively correlated with flow. Anaplerotic pathways contributed a fraction similar to J(TCA) in low- and high-flow areas, as demonstrated by isotopomer analysis after 60 min of [3-13C]pyruvate application. Mathematical model analysis of NMR data and relevant pool sizes revealed that J(TCA) and thus myocardial oxygen consumption (MVO2) in high-flow areas exceed values in low-flow areas at least threefold. Thus low and high metabolic states normally coexist within the well perfused heart, suggesting that there is considerable spatial heterogeneity of cardiac energy generation and work.