GLUTAMINE PEPTIDE - SUPPLEMENTED LONG-TERM TOTAL PARENTERAL-NUTRITION- EFFECTS ON INTRACELLULAR AND EXTRACELLULAR AMINO-ACID PATTERNS, NITROGEN ECONOMY, AND TISSUE MORPHOLOGY IN GROWING RATS

Glutamine (GLN) is a nonessential amino acid that is not included in c urrent regimens for parenteral nutrition because of its chemical insta bility. This study tested the hypothesis that GLN supplementation duri ng long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a g rowing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:c arbohydrate = 1:1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocalori c, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and ala nyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in whic h extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histo logic sections of liver and small-bowel mucosa (light and scanning ele ctron microscopy) were evaluated. Hepatic intracellular GLN concentrat ions were significantly lower in animals receiving GLN-free TPN (11.7 +/- 1.6 nmol/mg fat-free dry and solid tissue mass, n = 9) compared wi th both GLN-supplemented TPN (16.0 +/- 3.0, n = 7) and enteral feeding (18.2 +/- 1.8, n = 6) ( p < .001). Corresponding results were found f or intracellular GLN concentrations in skeletal muscle (TPN standard 1 2.5 +/- 3.1, TPN GLN 14.7 +/- 3.1, enteral control 17.3 +/- 2.3, p < . 05), intestinal mucosa, and spleen as well as for plasma concentration s. GLN supplementation was associated with a significant improvement i n nitrogen balance (cumulative nitrogen balance: 10.59 +/- 1.42 g of n itrogen per kilogram per 20 days) compared with animals on standard TP N (4.18 +/- 1.49). No differences were found for growth, serum protein s, and both liver and small intestinal histology. hi this rodent model , long-term standard TPN without GLN compared with GLN-supplemented TP N was associated with reduced GLN concentrations affecting skeletal mu scle, liver, and plasma. The GLN- containing dipeptides were adequatel y used in that they counteracted the decrease of extracellular and int racellular GLN concentrations and improved the nitrogen balance compar ed with the GLN-free TPN regimen.