Maintenance of Skeletal Muscle Intracellular Glutamine during Standard Surgical Trauma

Abstract

Skeletal muscle glutamine (GLN) concentration falls following injury and infection. In an attempt to prevent this decline and to characterize its influence on the efflux of amino acid (AA) from skeletal muscle, we administered varying quantities of AA (0,2, and 4 g/kg X day) as saline or AA solutions with or without GLN enrichment to 22 postoperative dogs. Plasma and muscle AA were determined before and 24 hr after standard laparotomy. Hindquarter AA efflux was measured at 6 and 24 hr. Skeletal muscle nitrogen declined in saline controls (69.8 +/- 8.5 vs 52.8 +/- 8.4 mmol/liter; p less than 0.01), largely due to the fall in intracellular GLN (21.48 +/- 3.21 vs 15.86 +/- 3.80; p less than 0.05). Similar alterations were seen in the animals receiving 2 g/kg. However, both intracellular nitrogen and GLN were maintained in animals receiving 4 g/kg, whether the AA solutions contained GLN or not (skeletal muscle nitrogen before 64.3 +/- 8.6 mmol/l vs 65.4 +/- 7.0 after, GLN 19.2 +/- 3.4 vs 19.9 +/- 3.0). Hindquarter AA efflux was reduced in those animals at 6 hr compared with saline-treated animals (-6.52 +/- 1.8 and -7.70 +/- 5.90 vs -19.05 +/- 4.06 mumol/kg X min; p less than 0.05). Intracellular GLN can be maintained during operative stress with adequate nitrogen infusion. Replacing 50% of the balanced AA solution with GLN resulted in equally effective maintenance of intracellular GLN levels and a comparable reduction in skeletal muscle AA efflux. Preservation of normal intracellular GLN levels with adequate AA nutrition may be essential for the conservation of muscle protein.

Glutamine kinetics and protein turnover in end-stage renal disease

“…Similarly, the alanine and glutamine concentration in the artery (29.8 vs.28.8%) declined more than that in the vein (12.3 vs. 19.1%) and muscle compartments (4.1 vs. 4.7%). Human and animal studies have suggested that the muscle glutamine pool positively influences protein synthesis (24,27). Furthermore, it is claimed that this correlation is specific for glutamine and has not been observed with any other amino acid (32).…”

Human Amino Acid and Protein Requirements: Current Dilemmas and Uncertainties

“…There is a striking direct correlation between glutamine concentration and the rate of protein synthesis in rat skeletal muscle in vivo (Jepson et al 1988). Glutamine infusions can reduce the post-operative efflux of amino acids for dog hind limb (Kapadia et al 1985) and can directly stimulate protein synthesis (MacLennon ef al. 1987) and inhibit protein degradation (MacLennon et al 1988) in muscle.…”

Glutamine Enhances Selectivity of Chemotherapy Through Changes in Glutathione Metabolism

“…[1][2][3][4][5][6][7][8] Toxicity to the tumorbearing host is seen from the disease and from chemotherapy treatment-related injury. Dose intensification of chemotherapy is thought to increase survival.9"'0 However, the limitation of intensifying chemotherapeutic regimens has become the severity of toxicity to the normal host tissues.'…”

“…'7 Glutathione is a potent ubiquitous antioxidant that also is an important factor in the metabolism of many drugs and endogenous substances. 8 '9 An important function of GSH is protection of critical cellular molecules. Toxicity of target tissue is a result of depletion oftissue GSH concentration and protein alkylation.…”