Assessing mitochondrial respiration in isolated hearts using 17O MRS

Ming Lu, Bharath Atthe, Gheorghe D. Mateescu, Chris A. Flask, Xin Yu

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10 Scopus citations

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 languageEnglish (US)
Pages (from-to)883-889
Number of pages7
JournalNMR in biomedicine
Volume25
Issue number6
DOIs
StatePublished - Jun 2012

Keywords

  • Energy-function relationship
  • Mitochondrial function
  • Myocardial metabolism
  • O spectroscopy
  • Oxygen consumption

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