Abstract 24033: Regional Assessment of Pyruvate Metabolism in the Remodeled Heart Using Dynamic Nuclear Polarization Carbon13 Magnetic Resonance

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Introduction: After infarction compensated remodeling of the left ventricular (LV) may be followed by adverse remodeling leading to heart failure. The mechanism of adverse remodeling maybe linked to the elevated wall stress in the dysfunctional myocardium adjacent to the infarct (border zone BZ). We hypothesize that increased BZ stress results in altered metabolism which could drive the transition from compensated to adverse remodeling. To evaluate BZ and remote metabolism we compared the regional uptake and intracellular conversion of 1-13C-pyruvate using hyperpolarized (HP) 13C MR.

Methods: An established pre-clinical posterolateral infarct model of LV remodeling was used to investigate region metabolism. To accurately measure regional metabolism, we developed implantable carbon-tuned surface coils placed on the epicardium over the BZ and remote regions (Fig. Top). A coronary catheter was placed for direct injection of the HP substrate to maximize deliver and eliminate cavity blood pool signal. MR was performed at 6-weeks post infarct with a spectra acquired every 1.5s for each region simultaneously during HP infusion under physiologic and DOB stress conditions. The resulting spectra from each coil were analyzed to measure lactate, alanine, bicarb, and total flux.

Results: Under physiologic (Pre-DOB) conditions the percent difference between remote and BZ lactate, alanine, and total flux was only slightly elevated in the remote region whereas bicarb flux was greater in BZ compared to remote (Fig. Bottom). DOB stress produced an increase in remote metabolite flux compared to BZ with lactate, alanine and total flux reaching significance and bicarb flux shifting from greater in BZ Pre-DOB to greater in remote.

Conclusion: These findings demonstrate an impaired metabolic response to pharmacologic stress in BZ myocardium which may provide a mechanism for the established association of mechanical stress and adverse cardiac remodeling following infarct.

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