Assessing mitochondrial respiration in isolated hearts using (17)O MRS

Area of Science:

• Cardiovascular Physiology
• Biophysics
• Metabolic Imaging

Background:

• Assessing cardiac mitochondrial function using (17)O MRI and MRS is challenging due to the difficulty in detecting metabolic H(2)(17)O amidst abundant natural H(2)(17)O.
• Existing methods face limitations in sensitivity and specificity for evaluating metabolic water production in cardiac tissue.

Purpose of the Study:

• To develop and validate a direct (17)O MRS approach for detecting metabolically produced H(2)(17)O in isolated rat hearts.
• To assess the feasibility and sensitivity of this method in response to varying cardiac workload induced by different calcium concentrations.

Main Methods:

• Isolated rat hearts were perfused with (17)O(2)-enriched buffer at normal and high calcium concentrations (1.5 mM and 2.5 mM) to simulate different workloads.
• Dynamic (17)O MRS was employed to monitor the production of H(2)(17)O.
• A compartment model was developed to quantify the myocardial oxygen consumption rate (MVO(2)) and myocardial (17)O(2) consumption rate (MV(17)O(2)).

Main Results:

• Myocardial oxygen consumption rate (MVO(2)) increased by 82% at high calcium concentrations, indicating increased cardiac workload.
• Dynamic (17)O MRS detected an accelerated H(2)(17)O signal increase at high calcium, correlating with elevated mitochondrial production.
• Model-derived MV(17)O(2) showed a 92% increase at high workload, consistent with measured MVO(2).
• Phosphocreatine to ATP ratios remained similar, indicating maintained energy balance despite increased metabolic activity.

Conclusions:

• Dynamic (17)O MRS is a sensitive tool for detecting altered metabolic rates in the heart.
• This method can effectively assess changes in cardiac workload and mitochondrial function.
• The developed approach holds promise for non-invasive evaluation of cardiac metabolic health.