To determine the cause of reduced urea synthesis in cirrhosis, absolute concentrations of phosphorus metabolites in the human liver have been measured in vivo with magnetic resonance (MR) spectroscopy. One-dimensional chemical shift imaging was used to obtain phosphorus-31 spectra from five healthy volunteers and five patients with alcoholic cirrhosis. A reference standard included in all studies enabled the calculation of absolute concentrations. In contrast to hepatic metabolite ratios, absolute concentrations reveal that in the cirrhotic patients, concentrations of adenosine triphosphate (ATP) were significantly reduced and concentrations of phosphomonoesters slightly reduced. Intracellular pH was unchanged. Histologic evidence suggests that the amount of ATP per cell was unchanged and could not account for the reduced urea production. Instead, urea synthesis depends on the functional liver cell mass, which was reduced by 31% in alcoholic cirrhosis. Quantitative in vivo P-31 MR spectroscopy of liver has potential clinical applications and can supplement the more generally used P-31 metabolite ratios.

No abstract

No abstract

We have developed an animal model to elucidate the acute effects of perfusion abnormalities on muscle metabolism induced by different density-defined classes of erythrocytes isolated from sickle cell anemia patients. Technetium-99m (9"'Tc)-labeled, saline-washed normal (AA), homozygous sickle (SS), or high-density SS (SS4) erythrocytes were injected into the femoral artery of the rat and quantitative 99fTc imaging, 31p magnetic resonance spectroscopy by surface coil at 2 teslas, and 'H magnetic resonance imaging at 0.15 tesla were performed. Between 5 and 25 p1 of SS4 cells was trapped in the microcirculation of the thigh (or 1-6 X 107 cells per cubic centimeter of tissue). In contrast, fewer SS discocytes (SS2) or AA cells were trapped (an equivalent packed cell volume of less than 6.7 p1 and 0.3 pl, respectively). After injection of SS4 cells an initial increase in inorganic phosphate was observed in the region of the thigh served by the femoral artery, intracellular pH decreased, and subsequently the proton relaxation time T, reached a broad maximum at 18-28 hr. When T, obtained at this time was plotted against the volume of cells trapped, an increase of T, over the control value of411 ± 48 msec was found that was proportional to the number of cells trapped. We conclude that the densest SS cells are most effective at producing vasoocclusion. The extent of the change detected by 'H magnetic resonance imaging is dependent on the amount ofcells trapped in the microcirculation and the magnitude of the initial increase of inorganic phosphate.

No abstract