INVIVO HEPATIC ENERGY-METABOLISM DURING THE PROGRESSION OF ALCOHOLIC LIVER-DISEASE - A NONINVASIVE P-31 NUCLEAR MAGNETIC-RESONANCE STUDY IN RATS

We investigated serially in vivo the rations of phorylated metabolites and the intracellular PH in the livers of rats fed ethanol chronically to evaluate the relation between changes in energy metabolism and the progression of alcoholic liver disease with 31P nuclear magnetic resonance spectroscopy. 31P nuclear magnetic resonance spectra of the liver were acquired noninvasively from rats pair‐fed a nutritionally adequate liquid diet containing ethanol or an isocaloric amount of dextrose with an implanted intragastric cannula of dextrose with an implanted intragastric cannula for up to 24 wk. A high blood alcohol level was constantly maintained. The spectra were obtained using a surface coil combined with a ferrite screen to eliminate nuclear magnetic resonance signals derived from the superficial muscles. Contaminating 31P nuclear magnetic resonance signals. Contaminating 31P nuclear magnetic resonance signals arising from abdominal tissues other than the liver were climinated from the spectra by digital subtraction. Throughout the study the inorganic phosphate/β‐ ATP peak area ratio observed in alcohol‐fed rats was found to be consistently elevated in comparison with the control rats ( at 3 to 5 wk alcohol‐fed rats = 1.20 ± 0.10, control rats = 0.78 ± 0.04, p < 0.05,; at 22 to 24 wk alcohol‐fed rats = 1.23 ± 0.10, control rats = 0.81 ± 0.06, p < 0.05.; mean ± S. E.). The phosphomonoesters/β‐ATP ratio tended to be higher in alcohol‐fed rats when compared with control rats. The intracellular pH measured by the chemical shift of the inorganic phosphate peak showed no significant differences between alcohol‐fed rats and control rats. Steatosis, necrosis, inflammation and fibrosis were observed to be progressively more severe in the monthly liver biopsy speciments from alcohol‐fed rats, so that the pathological score significantly increased with the duration of feeding (r = 0.623, p <0.001). The inorganic phosphate / β‐ATP ratio was not significantly correlated with the changing pathological score, since the increased inorganci phosphate/β ‐ATP ratios remained constant over the duration of feeding. This observation suggests that the increase in the inorganic phosphate/β‐ATP rations is a primary effect of chronic ethanol feeding rather than a result of the workesening morphological changes observed in the liver. This low energy state in the liver may contribute to the pathogenesis of alcoholic liver disease. (HEPATOLOGY 1990; 11: 65–73.) Copyright © 1990 American Association for the Study of Liver Diseases