Abstract
The application of 17O MRI and MRS for the evaluation of cardiac mitochondrial function has been limited because of the challenge of detecting metabolic H 2 17O in the vast background of naturally abundant H 2 17O. In this study, we have developed a direct 17O MRS approach to examine the feasibility and sensitivity of detecting metabolically produced H 2 17O in isolated rat hearts perfused with 17O 2-enriched Krebs-Henseleit buffer containing normal (1.5mm) and high (2.5mm) calcium (Ca 2+) concentrations to induce high workload. Consistent with increased workload at high Ca 2+ concentration, the measured myocardial oxygen consumption rate (MVO 2) increased by 82%. Dynamic 17O MRS showed an accelerated increase in the H 2 17O signal at high Ca 2+ concentration, suggesting increased mitochondrial production of H 2 17O in concordance with the increased workload. A compartment model was developed to describe the kinetics of H 2 17O production as a function of MVO 2. The myocardial 17O 2 consumption rate (MV 17O 2) was determined by least-squares fitting of the model to the NMR-measured H 2 17O concentration. Consistent with the measured MVO 2, the model-determined MV 17O 2 showed a 92% increase at high Ca 2+ concentration. The increase in metabolic activity at high workload allowed the balance between ATP production and utilization to be maintained, leading to a similar phosphocreatine to ATP ratio. These results demonstrate that dynamic 17O MRS can provide a valuable tool for the detection of an altered metabolic rate associated with a change in cardiac workload.
Original language | English (US) |
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Pages (from-to) | 883-889 |
Number of pages | 7 |
Journal | NMR in biomedicine |
Volume | 25 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2012 |
Keywords
- Energy-function relationship
- Mitochondrial function
- Myocardial metabolism
- O spectroscopy
- Oxygen consumption