Key result
In vivo cardiac PCr/ATP ratio did not correlate with ex vivo ADP-stimulated mitochondrial respiration rates (R2 < 0.005, p = 0.74), suggesting mitochondrial function is not the only determinant of cardiac energy status.
Why the study?
It was suggested that the cardiac PCr/ATP ratio reflects cardiac mitochondrial function, but whether it can be used as an in vivo marker required investigation.
Does in vivo cardiac PCr/ATP ratio correlate with ex vivo cardiac mitochondrial function in patients undergoing open-heart surgery?
Observational (n=38)
No
Does in vivo cardiac PCr/ATP ratio correlate with ex vivo cardiac mitochondrial function in patients undergoing open-heart surgery?
In vivo cardiac PCr/ATP ratio does not directly correlate with ex vivo mitochondrial respiratory capacity, suggesting that other factors, such as creatine availability, also determine cardiac energy status.
Answers are grounded in this paper and cite their sources.
No correlation with ex vivo mitochondrial respiration cautions against using PCr/ATP as a direct mitochondrial marker; leaves open its value as an integrated cardiac energy readout.
Cardiac energy status, measured as phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio with 31P-Magnetic Resonance Spectroscopy (31P-MRS) in vivo, is a prognostic factor in heart failure and is lowered in cardiometabolic disease. It has been suggested that, as oxidative phosphorylation is the major contributor to ATP synthesis, PCr/ATP ratio might be a reflection of cardiac mitochondrial function. The objective of the study was to investigate whether PCr/ATP ratios can be used as in vivo marker for cardiac mitochondrial function. We enrolled thirty-eight patients scheduled for open-heart surgery in this study. Cardiac 31P-MRS was performed before surgery. Tissue from the right atrial appendage was obtained during surgery for high-resolution respirometry for the assessment of mitochondrial function. There was no correlation between the PCr/ATP ratio and ADP-stimulated respiration rates (octanoylcarnitine R 2 < 0.005, p = 0.74; pyruvate R 2 < 0.025, p = 0.41) nor with maximally uncoupled respiration (octanoylcarnitine R 2 = 0.005, p = 0.71; pyruvate R 2 = 0.040, p = 0.26). PCr/ATP ratio did correlate with indexed LV end systolic mass. As no direct correlation between cardiac energy status (PCr/ATP) and mitochondrial function in the heart was found, the study suggests that mitochondrial function might not the only determinant of cardiac energy status. Interpretation should be done in the right context in cardiac metabolic studies.
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Wit‐Verheggen et al. (2023) conducted an observational in Patients scheduled for open-heart surgery (n=38). Cardiac PCr/ATP ratio was evaluated on Correlation between PCr/ATP ratio and ADP-stimulated respiration rates (octanoylcarnitine) (R2 < 0.005, p=0.74). In vivo cardiac PCr/ATP ratio did not correlate with ex vivo ADP-stimulated mitochondrial respiration rates (R2 < 0.005, p = 0.74), suggesting mitochondrial function is not the only determinant of cardiac energy status.
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