Inhibition of bile flow in the isolated perfused rat liver by a synthetic parenteral amino acid mixture: associated net amino acid fluxes.
To identify a role for amino acids in cholestasis associated with total parenteral nutrition, we measured bile formation by the isolated perfused rat liver in the presence and absence of added amino acids. All livers were infused constantly with sodium [14C]taurocholate (0.28 mumoles per min) for 90 min. At 40 min, a primed-constant infusion of a synthetic L-amino acid mixture (121 + 19.3 mumoles of N per min) was administered for an additional 50 min. Mean bile flow rates during the amino acid infusion were reduced from 15.4 microliter per min per 10 gm liver weight to 10.4 microliter per min per 10 gm (p less than 0.005). There was no significant change during saline infusion of control livers, and there was no significant difference in perfusate osmolalities in the two groups. Although biliary recovery of infused taurocholate was slightly lower in the experimental perfusions than in controls (95.3% vs. 101.7%, p less than 0.05), there was no significant reduction in taurocholate excretion rate during the infusion in either group. Bile flow changes were related to ambient concentrations and net fluxes of individual amino acids in the perfusate. Of the 14 infused amino acids, glycine and arginine achieved levels greater than 3 times greater than reported physiological postprandial portal venous concentrations in the rat, and together constituted about 25% of the 90-min perfusate amino acids (8.3 mM). The highest net hepatic uptake was for glycine (125 mumoles per hr per 10 gm), which was almost 50% of its infusion rate.(ABSTRACT TRUNCATED AT 250 WORDS)
D000596:Amino Acids / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D002779:Cholestasis / Q000209:etiology* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010288:Parenteral Nutrition / Q000009:adverse effects*; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids