In CHD, MDE by MRI quantifies MF that not only can be detected in the early asymptomatic stages but parallels well-established prognostic factors and provides unique information for clinical disease staging.

No abstract

clinicaltrials.org Identifier: NCT02432885.

Although the tricarboxylic acid (TCA) cycle is the prime means of carbon metabolism for energy generation in normal myocardium, the noninvasive quantification of TCA cycle flux in intact cardiac tissues is difficult. A novel approach for estimating citric acid cycle flux using 13C nuclear magnetic resonance (NMR) is presented and evaluated experimentally by comparison with measured myocardial oxygen consumption over a wide range of cardiac contractile function in intact, beating rat hearts. Continuous series of 13C NMR spectra, obtained after the introduction of [2-13C]acetate as substrate, quantified the time course of 13C appearance in the carbon positions of myocardial glutamate, which are sequentially enriched via citric acid cycle metabolism. A TCA cycle flux parameter was calculated using the premise that TCA cycle flux is inversely proportional to the time difference between 13C appearance in the C-4 and C-2 positions of glutamate (glutamate delta t50 [minutes]), which are enriched in subsequent "turns" of the TCA cycle. This TCA cycle flux parameter, termed KT, correlated strongly with myocardial oxygen consumption over a range of developed pressures in hearts perfused with 5 mM acetate (r = 0.98, p less than 0.001), as well as in separate studies in hearts perfused with 5 mM glucose and 0.5-0.8 mM acetate (r = 0.94, p less than 0.001). Results of numerical modeling of 13C glutamate kinetics suggest that this TCA cycle flux parameter, KT, is relatively insensitive to changes in metabolite pool sizes that could occur during metabolism of other substrates or during conditions of altered oxygen availability. Additional studies in separate hearts indicated that the time course of 13C appearance in citrate, which is predominantly mitochondrial in the rat heart, is similar to that in glutamate, further supporting the premise that the described 13C NMR parameters reflect mitochondrial citric acid cycle activity in intact cardiac tissues.

The influence of metabolic substrate on contractile strength, myocardial oxygen consumption (MVO2), high- and low-energy phosphate levels, and intracellular pH were determined in isovolumically contracting isolated rat hearts perfused with solutions containing either glucose or hexanoate at both high and low coronary perfusion pressures (CPP). Contractile strength was not significantly influenced by substrate at a CPP of 80 mmHg. As coronary flow was decreased, developed pressure measured at a fixed left ventricular volume (LVV) was lower during hexanoate than glucose perfusion. The relationship between MVO2 and mechanical work determined at a CPP of 80 mmHg over a range of LVVs was shifted upward in a parallel manner when substrate was switched from glucose to hexanoate. The MVO2-work relationship measured at a fixed LVV but over a range of coronary flows (7-20 ml/min) was also parallel shifted upward on switching from glucose to hexanoate. Basal MVO2 was greater during hexanoate than glucose perfusion by an amount that accounted for two-thirds the total increase in MVO2 observed between the substrates under unloaded beating conditions. The remainder of the difference was attributed to increased energy requirements for excitation-contraction coupling. Inorganic phosphate concentrations increased more and phosphocreatine concentrations decreased more during low-flow conditions (3 ml/min) when hearts were perfused with hexanoate compared with glucose. Thus hexanoate decreases myocardial efficiency compared with glucose in large part by increasing non-work-related oxygen demands. This inefficiency impacts adversely on contractile strength and high-energy phosphate concentrations at low coronary flows.