Table 1.
Comparison of metabolic flux and physiological parameters assessed in 12-week-old C57BL/10 and mdx mouse hearts perfused with 13C-labeled substrates.
Measured parameters | mdx vs. C57BL/10 (ratio) |
---|---|
(1) Metabolic flux parameters assessed at 30 min | |
(A) Cytosolic | ↑(1.62)* |
Glycolysis (production of lactate and pyruvate) | |
(B) Mitochondria | |
(i) Relative contribution of substrates to citrate synthesis | |
–Carbohydrate oxidation: pyruvate decarboxylation (PDC/CS) | ↑ (2.20)** |
–Fatty acid oxidation: oleate β-oxydation (OLE/CS) | ↓ (0.73)* |
–Oxidation of other substrates (OS/CS) | NS |
–Anaplerosis: pyruvate carboxylation (PC/CS) | ↓ (0.81)* |
(ii) Citric acid cycle-related parameters | |
–Citric acid cycle intermediate levels | ↓ (0.66)** |
–Aconitase activity | ↓ (0.72)* |
–Citrate synthase activity | NS |
–Calculated ATP production rates | ↑ (1.17)* |
(2) Physiological parameters assessed at 25–30 min | |
–Aortic flow | ↑ (0.83)* |
–Coronary flow | NS |
–Left ventricular systolic pressure | ↓ (0.90)* |
–Left ventricular end diastolic pressure | NS |
–Heart rate | NS |
–dP/dtmax | ↓ (0.84)** |
–dP/dtmin | ↓ (0.87)* |
–Oxygen consumption | ↑ (1.18)** |
–Lactate dehydrogenase release | ↑ (2.60)** |
Metabolic and functional data are from [8]. The following metabolic parameters were assessed in working hearts perfused for 30 min with physiological concentrations of carbohydrates (11 mM glucose, 1.5 mM lactate and 0.2 mM pyruvate) and a fatty acid (0.4 mM oleate bound to albumin) using 13C-labeled substrates and mass isotopomer analysis by gas chromatography-mass spectrometry: (A) Glycolysis reflecting the production of lactate and pyruvate from 13C-glucose (μmol×min−1). (B.i) Substrate flux ratios reflecting the contribution of exogenous fatty acids (oleate) and carbohydrates (CHOs: lactate, pyruvate and glucose) to citrate formation via (i) acetyl-CoA (energy) from oleate β-oxidation (OLE) and pyruvate decarboxylation (PDC), or (ii) oxaloacetate (anaplerosis) from pyruvate carboxylation (PC), all expressed relative to citrate synthesis (CS); (B.ii) Tissue concentration of citric acid cycle (CAC) intermediates (in μmol×g wet weight−1), tissue aconitase and citrate synthase activity (μmol×min−1×mg protein−1) and calculated ATP production rates.
p<0.05,
p< 0.001 for mdx versus control mouse hearts; NS: not significant.