Abstract 12300: Heterogeneity of ATP Turnover Rates in the LV of Swine Hearts With Post-infarction Remodeling
Objective Alterations in ATP synthetic capacity is thought to contribute to the dysfunction of the failing heart. However, standard 31P magnetic resonance spectroscopy-magnetization saturation transfer (MRS-MST) techniques cannot measure this directly due to low levels of inorganic phosphate (MPi) in the in vivo heart. Therefore, we developed a novel indirect MRS-MST approach and examined in vivo myocardial ATP turnover rate constant (kr,ATP, ATP→ADP +Pi).
Methods & Results In the new approach we subtract the confounding creatine kinase (CK) reaction (ATP↔CK) from the MRS-MST measurement of total ATP turnover rate (ATP→ADP+Pi and ATP→CK) so that no quantification of MPi is required. The method was validated using swine skeletal muscle (n=4), demonstrating equal results as compared to conventional direct MRS-MST approach. We then measured kr,ATP in swine hearts with postinfarction LV remodeling (LVR, n=9, 4 weeks post myocardial infarction), and in size-matched normal swine hearts (n=11, NL). In NL hearts, the kr ATP was found to be tightly correlated with cardiac workstate (increased by catecholamine infusion) as evidenced by a linear relationship vs. rate-pressure-product (RPP). In BZ of LVR hearts kr,ATP was significantly reduced (baseline workstate values: 0.07±0.03 (MI) vs. 0.18±0.04 (NL) s-1, a 61% reduction, p<0.05) and did not increase in response to catecholamine stimulation. In contrast, the rate constants of the forward creatine kinase reaction (kf,CK, PCr→ATP) were comparable in both groups (0.37±0.03 (NL) vs. 0.34±0.03 (MI) s-1, p=NS).
Conclusion We have established a novel indirect MRS-MST approach to estimate the in vivo myocardial ATP turnover rate in a swine model. The LV with post-infarction remodeling is metabolically heterogeneous and kr,ATP reductions in BZ precede the reductions of kf,CK (observed in failing hearts). The down-regulation of kr,ATP in the BZ may reflect greater wall stresses and concomitantly greater activation of adverse molecular signaling pathways in that region.
- © 2012 by American Heart Association, Inc.