Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo

Lorenzo Rossaro, Vincenzo Mazzaferro, Carlo L. Scotti-Foglieni, Donald S. Williams, Elena Simplaceanu, Virgil Simplaceanu, Antonio Francavilla, Thomas E. Starzl, Chien Ho, David H. Van Thiel

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12 Scopus citations

Abstract

The effect of cyclosporin A on the hepatic energy status and intracellular pH of the liver and its response to a fructose challenge has been investigated using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in dogs. Three experimental groups were studied: (a) control dogs (n = 5), (b) dogs 4 days after the creation of an end-to-side portacaval shunt (n = 5), and (c) dogs 4 days after portacaval shunt and continuous infusion of cyclosporin A (4 mg/kg/day) by way of the left portal vein (portacaval shunt plus cyclosporin A, n = 5). The phosphorus-31 nuclear magnetic resonance spectra were obtained at 81 MHz using a Bruker BIOSPEC II 4.7-tesla nuclear magnetic resonance system equipped with a 40-cm horizontal bore superconducting solenoid. The phosphomonoesters (p < 0.01), inorganic phosphate and ATP levels (p < 0.05) were decreased significantly in portacaval shunt-treated and in portacaval shunt-plus-cyclosporin A-treated dogs compared with unshunted control dogs. After a fructose challenge (750 mg/kg body wt, intravenously), fructose-1-phosphate metabolism was reduced in portacaval shunt-treated dogs compared with either the normal or portacaval shunt-plus-cyclosporin A-treated dogs (p < 0.05). Both portacaval shunt- and portacaval shunt-plus-cyclosporin A-treated dogs demonstrated a reduced decline in ATP levels after fructose infusion when compared with the controls (p < 0.05). Immediately after the fructose challenge, the intracellular pH decreased from 7.30 ± 0.03 to 7.00 ± 0.05 in all animals (p < 0.01) and then gradually returned to normal over 60 min. These data, obtained in vivo using phosphorus-31 nuclear magnetic resonance spectroscopy of the liver after a portacaval shunt, suggest that: (a) the energy status of the liver is reduced in dogs with a portacaval shunt compared with that of normal controls and (b) cyclosporin A treatment ameliorates the reduction in hepatic metabolism normally observed after a fructose challenge to the liver with a portacaval shunt.

Original languageEnglish (US)
Pages (from-to)780-785
Number of pages6
JournalHepatology
Volume13
Issue number4
StatePublished - Apr 1991
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

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    Rossaro, L., Mazzaferro, V., Scotti-Foglieni, C. L., Williams, D. S., Simplaceanu, E., Simplaceanu, V., Francavilla, A., Starzl, T. E., Ho, C., & Van Thiel, D. H. (1991). Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo. Hepatology, 13(4), 780-785.