PCr/ATP Ratios and Mitochondrial Function in The Heart. A Comparative Study in Humans. release_fouwezyvrvfktafrifmk6fo3y4

Abstract

<jats:title>Abstract</jats:title> <jats:bold>Objectives</jats:bold> The objective of the study was to validate PCr/ATP ratios as an <jats:italic>in vivo</jats:italic> marker for cardiac mitochondrial function.<jats:bold>Background</jats:bold> Cardiac energy status, measured as PCr/ATP ratio with <jats:sup>31</jats:sup>P-MRS <jats:italic>in vivo</jats:italic>, was shown to be a prognostic factor in heart failure and is lowered in cardiometabolic disease. As mitochondrial function is also hampered in these diseases and oxidative phosphorylation is the major contributor to ATP synthesis, the PCr/ATP ratio might be a reflection of cardiac mitochondrial function.<jats:bold>Methods</jats:bold> Thirty-eight patients scheduled for open heart surgery were enrolled in this study. Before surgery, cardiac <jats:sup>31</jats:sup>P-MRS was performed. During surgery, tissue specimens from the right atrial appendage were obtained for the <jats:italic>ex vivo</jats:italic> assessment of mitochondrial function using high-resolution respirometry.<jats:bold>Results</jats:bold> The patient population included was heterogenous resulting in wide ranges of PCr/ATP ratios and ADP-stimulated respiration rates (PCr/ATP ranging from 0.533 to 1.717; ADP-stimulated respiration rates ranging from 28.5 to 94.6 pmol/mg/s). Correlation analysis however showed no relationship between PCr/ATP and ADP-stimulated respiration rates fueled by various substrates (octanoylcarnitine R<jats:sup>2</jats:sup> &lt; 0.005, p = 0.74; pyruvate R<jats:sup>2</jats:sup> &lt; 0.025, p = 0.41). Also, no correlations between PCr/ATP and maximally uncoupled respiration were found (octanoylcarnitine R<jats:sup>2</jats:sup> = 0.005, p = 0.71; pyruvate R<jats:sup>2</jats:sup> = 0.040, p = 0.26).<jats:bold>Conclusions</jats:bold> Our results do not support the use of cardiac energy status (PCr/ATP) as a surrogate marker of mitochondrial function in the heart. The dissociation of the two parameters in the present study suggests that mitochondrial function is not the only determinant of cardiac energy status.<jats:bold>Condensed abstract</jats:bold>This study does not support the use of <jats:italic>in vivo</jats:italic> cardiac energy status (PCr/ATP ratio) as a surrogate marker of <jats:italic>ex vivo</jats:italic> mitochondrial function (maximal oxidative respiration). Although both PCr/ATP and mitochondrial function are reduced in cardiovascular disease, the dissociation of the two parameters in the present study shows that PCr/ATP is determined by more factors than only mitochondrial function. Hence, PCr/ATP is not a good marker for mitochondrial function, but it can be a valuable marker for cardiometabolic health in cardiometabolic studies.<jats:bold>Trial registration</jats:bold>: https://clinicaltrials.gov (NCT03049228).
In application/xml+jats format

Archived Files and Locations