Assessing mitochondrial respiration in isolated hearts using 17 O MRS

The application of 17 O MRI and MRS for the evaluation of cardiac mitochondrial function has been limited because of the challenge of detecting metabolic H 2 17 O in the vast background of naturally abundant H 2 17 O. In this study, we have developed a direct 17 O MRS approach to examine the feasibility and sensitivity of detecting metabolically produced H 2 17 O in isolated rat hearts perfused with 17 O 2 ‐enriched Krebs–Henseleit buffer containing normal (1.5 m m ) and high (2.5 m m ) 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 17 O MRS showed an accelerated increase in the H 2 17 O signal at high Ca 2+ concentration, suggesting increased mitochondrial production of H 2 17 O in concordance with the increased workload. A compartment model was developed to describe the kinetics of H 2 17 O production as a function of MVO 2 . The myocardial 17 O 2 consumption rate (MV 17 O 2 ) was determined by least‐squares fitting of the model to the NMR‐measured H 2 17 O concentration. Consistent with the measured MVO 2 , the model‐determined MV 17 O 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 17 O MRS can provide a valuable tool for the detection of an altered metabolic rate associated with a change in cardiac workload. Copyright © 2011 John Wiley & Sons, Ltd.