Abstract 17445: Transmurally Differentiated Measurements of Myocardial ATP Hydrolysis Rate in Vivo
Difficulty in measuring myocardial Pi has been a major barrier in elucidating the speculation that decreased reserve of myocardial ATP turnover rate contributes to the progression of LV, a subject still of much debate. Recently, a novel method of extracting the ATP hydrolysis rate forgoing Pi measurement was introduced (Xiong et al, Circ 2013). This study is an extension to compare the transmural distribution of forward creatine kinase (CK) reaction (kPCr→ATP) and ATP turnover rate (kATP→Pi) in the LV myocardium of normal swine (N = 10). Bioenergetics was measured utilizing one-dimension chemical shift imaging (1D-CSI) magnetic resonance 31P spectroscopy (MRS) at 9.4T. Three sets of magnetization saturation (MST) measurements; 1D-CSI, 1D-CSI with ATP saturation and 1D-CSI with PCr-Pi double saturation (FOV 4cm, nPE = 17, nt = 12), were acquired. The kPCr→ATP and kATP→Pi of the epi and endo layers are given by:
kPCr→ATP = (Mc,PCr/Ms,PCr - 1)/T1,PCrnom
kATP→Pi = (Mc,ATP/Ms,ATP - 1)/T1,ATPnom - Mo,ATP/Mo,ATP* kPCr→ATP
where Mo,PCr(ATP) is fully relaxed magnetization without saturation of ATP(PCr and Pi), Mc,PCr(ATP) and Ms,PCr(ATP) is partially relaxed magnetization with and without saturation of ATP(PCr and Pi), and T1,PCr(ATP)nom is nominal T1 under partial relaxation. Under basal conditions, there was no significant difference between epi and endo for both fluxPCr→ATP (4.4±0.53 vs. 4.57±0.84, μmol/g/s) and fluxATP→Pi (1.11±0.12 vs. 1.12±0.13, μmol/g/s), where fluxPCr→ATP(PCr→ATP) = [ATP(PCr)]*kATP→Pi(PCr→ATP) and [PCr] was back-calculated using the measured PCr-to-ATP ratio based on ATP level of 5.3 μmol/g according to our earlier report. Under high workload where rate pressure product increased 2.5-fold, fluxPCr→ATP showed no significant change in both subepi- and subendo- layers (epi: 4.52±0.47; endo: 3.68±0.16, p=NS VS baseline), while fluxATP→Pi increased significantly (epi: 2.35±0.27; endo: 2.21±0.08, p<0.01 VS Baseline). Thus, in the in vivo normal heart, increase of cardiac workstate is accompanied by linear increase of ATP flux rate with no changes in CK flux rate. There are no significant differences between epi VS endo concerning the ATP flux rate or CK flux rate in both baseline and high cardiac works states.
Author Disclosures: A. Jang: None. W. Cui: None. P. Zhang: None. J. Zhang: None.
- © 2014 by American Heart Association, Inc.