Proton-decoupled myocardial 31P NMR spectroscopy reveals decreased PCr/Pi in patients with severe hypertrophic cardiomyopathy.

Disturbed myocardial energy metabolism may occur in patients with primary hypertrophic cardiomyopathy (HCM). A noninvasive way to gain insight into cardiac energy metabolism is provided by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectroscopy with proton decoupling was performed in 13 patients aged 13-36 years with HCM on a 1.5 T Magnetom with a double resonant surface coil. A 2D chemical shift imaging (CSI) sequence in combination with slice selective excitation was used to acquire spectra of the anteroseptal region of the left ventricle (volume element: 38 mL). The chemical shifts of the phosphorus metabolites, intracellular pHi, and coupling constants J(alphabeta) and J(gammabeta) were calculated. Peak areas of 2,3-diphosphoglycerate (DPG), Pi, and adenosine triphosphate (ATP) were determined and corrected for blood contamination, saturation, and differences in nuclear Overhauser enhancements (NOE). The maximum thickness of the interventricular septum (IVSmax) was determined from tomographic long-axis images and expressed as number of standard deviations above the mean of the normal population (Z score). The patients were then divided into 2 groups: 6 patients with moderate HCM (HCMm, Z score < or = 5) and 7 patients with severe HCM (HCMs, Z score > 5). No differences between both groups and a control group of healthy volunteers (n = 16) were found with respect to phosphocreatine (PCr)/gamma-ATP ratio, pHi, or the coupling constants. Only the PCr/Pi ratio differed significantly from the control group (HCM(all), alpha < 0.05, HCMs, alpha < 0.02, 2-sided U test). The decrease of the PCr/Pi ratio in patients with HCM is probably caused by ischemically decreased oxygen supply in the severely hypertrophied myocardium.

Phosphorus J-coupling constants of ATP in human brain.

Proton decoupled 31P NMR spectroscopy of the occipital brain of healthy volunteers was performed with a 1.5 T whole-body imager. By use of two-dimensional chemical-shift imaging in combination with slice-selective excitation well resolved localized spectra (38 ml) were obtained within 34 min from which the homonuclear 31P-31P J-coupling constants of ATP could be determined: J(gammabeta) = 16.1 Hz +/- 0.2 Hz and J(alphabeta) = 16.3 Hz +/- 0.1 Hz (mean +/- SEM, n = 14). Both, the J-coupling constants and the chemical-shift difference between alpha- and beta-ATP (delta(alphabeta) = 8.61 ppm +/- 0.01 ppm) were used to calculate the concentration of intracellular free magnesium. The concentrations are 0.39 mM +/- 0.09 mM by using the average of both coupling constants of each spectrum, which is in fair agreement with 0.32 mM +/- 0.01 mM obtained from the chemical shift of alpha and beta phosphate resonances, which is the more accurate result.

31P NMR studies of human soleus and gastrocnemius show differences in the J gamma beta coupling constant of ATP and in intracellular free magnesium.

Localized proton decoupled 31P in vivo NMR spectroscopy of the human calf muscle was performed using a 1.5-T whole-body imager and the slice selective two-dimensional chemical-shift-imaging (2D-CSI) technique. The 31P-31P coupling constants and the chemical shifts of ATP were compared in gastrocnemius and soleus. Significant differences were found in the coupling constant J gamma beta: (18.1 +/- 0.7) Hz versus (17.1 +/- 0.6) Hz (means +/- SD, P < 10-5). Differences were also observed in the chemical shift separation delta alpha beta between the alpha- and beta-ATP signal: (8.498 +/- 0.023) ppm versus (8.522 +/- 0.222) ppm (p < 0.001) in gastrocnemius and soleus, respectively. A higher [MgATP]/[ATPfree] ratio and a significantly higher level of intracellular free magnesium of (0.52 +/- 0.06) mM in gastrocnemius versus (0.46 +/- 0.05) mM in soleus (p < 0.001) can be derived based on delta alpha beta and KDMgATP. Heterogeneity needs to be taken into account in clinical studies on magnesium by NMR methods in calf muscle. The coupling constant J gamma beta provides additional information, possibly on enzymatic processes, and correlates with [Mg2+free]. The detailed analysis of muscles with different fiber type characteristics lends support to the significance of this parameter in evaluating metabolism. The data reported can be used as prior knowledge for fits in which the coupling constants are set to a fixed value.