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 current regimens for parenteral nutrition because of its chemical instability. This study tested the hypothesis that GLN supplementation during long-term total parenteral nutrition (TPN) (3 weeks) would enhance GLN availability, thereby improving nitrogen economy and growth in a growing rat model: Standard TPN delivering 300 kcal/kg per day (lipid:carbohydrate = 1:1) including 2.1 g of nitrogen per kilogram per day in an all-in-one solution was compared with an isonitrogenous, isocaloric, and isovolemic TPN regimen with 0.29 g of nitrogen per kilogram per day substituted by GLN derived from the dipeptides glycyl-GLN and alanyl-GLN (TPN GLN). Enterally fed controls were included. Analysis was confined to nonbacteremic animals with negative blood culture, in which extracellular and intracellular amino acid concentrations including GLN, nitrogen balance, serum protein concentrations, growth, and histologic sections of liver and small-bowel mucosa (light and scanning electron microscopy) were evaluated. Hepatic intracellular GLN concentrations 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 with 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 for intracellular GLN concentrations in skeletal muscle (TPN standard 12.5 +/- 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 concentrations. GLN supplementation was associated with a significant improvement in nitrogen balance (cumulative nitrogen balance: 10.59 +/- 1.42 g of nitrogen per kilogram per 20 days) compared with animals on standard TPN (4.18 +/- 1.49). No differences were found for growth, serum proteins, and both liver and small intestinal histology. hi this rodent model, long-term standard TPN without GLN compared with GLN-supplemented TPN was associated with reduced GLN concentrations affecting skeletal muscle, liver, and plasma. The GLN- containing dipeptides were adequately used in that they counteracted the decrease of extracellular and intracellular GLN concentrations and improved the nitrogen balance compared with the GLN-free TPN regimen.