Alanyl-Glutamine-Supplemented Total Parenteral Nutrition Improves Survival and Protein Metabolism in Rat Protracted Bacterial Peritonitis Model

Abstract

Background: The effects of glutamine-enriched total parenteral nutrition (TPN) solution on survival, and protein turnover in the whole body and in individual organs were investigated in a rat protracted peritonitis model. Methods: Twenty-three rats underwent venous catheter insertion. Osmotic pumps were implanted in the peritoneal cavity to allow continuous delivery of Escherichia coli (4 × 10⁸ CFU/d). The conventional TPN group received a conventional amino acid solution. The Ala-Gln TPN group received an alanyl-glutamine-enriched TPN solution. The two TPN solutions were isocaloric and isonitrogenous. Results: Over the 5 days of TPN treatment, the survival rate of the Ala-Gln group was significantly higher than that of the conventional group. The Ala-Gln group tended to have increased whole-body protein turnover compared with the conventional group. Fractional protein synthetic rates (FSR) in the liver and gastrocnemius muscle of the Ala-Gln group were significantly higher than those of the conventional group. The serum glutamine concentration correlated positively with the FSR of both liver and muscle. The Ala-Gln group showed significantly greater mucosal height and mitoses per crypt, in the small intestine, than did the conventional group. Conclusions: Our results suggested that, in comparison with standard glutamine-free TPN, Ala-Gln-supplemented TPN increases protein synthesis in the liver and skeletal muscle, protects the morphology of the intestinal mucosa, and improves survival in protracted bacterial peritonitis. Ala-Gln supplementation may be useful in septic patients. (Journal of Parenteral and Enteral Nutrition 20:417-423, 1996)

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References

Souba WW , Smith RJ , Wilmore DW : Glutamine metabolism by the intestinal tract. JPEN 9:608-617, 1985

Calder PC : Glutamine and the immune system. Clin Nutr 13:2-8, 1994

Hammarqvist F. , Wernerman J. , Ali R. , et al: Addition of glutamine to total parenteral nutrition after elective abdominal surgery spares free glutamine in muscle, counteracts the fall in muscle protein synthesis, and improves nitrogen balance . Ann Surg 209:455-461, 1989

Stehle P. , Zander J. , Mertes N. , et al: Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery. Lancet 1:231-233, 1989

Wernerman J. , Hammarqvist F. , Ali MR , et al: Glutamine and ornithinealpha-ketoglutarate but not branched-chain amino acids reduce the loss of muscle glutamine after surgical trauma. Metabolism 38(8 Suppl 1):63-66, 1989

Sgana G. , Siegel JH , Brown G. , et al: Reprioritization of hepatic plasma protein release in trauma and sepsis. Arch Surg 120:187-199, 1985

Hasselgren PO , Jagenburg R. , Karlstrom K. , et al: Changes of protein metabolism in liver and skeletal muscle following trauma complicated by sepsis . J Trauma 24:224-228, 1984

Millward DJ , Jepson MM , Omer A. : Muscle glutamine concentration and protein turnover in vivo in malnutrition and in endotoxemia. Metabolism 38(8 Suppl 1):6-13, 1989

Souba WW , Herskowitz K. , Klimberg VS , et al: The effects of sepsis and endotoxemia on gut glutamine metabolism . Ann Surg 211:543-551, 1990

10.

Salloum RM , Copeland EM , Souba WW : Brush border transport of glutamine and other substrates during sepsis and endotoxemia. Ann Surg 213:401-410, 1991

11.

Austgen TR , Chen MM , Salloum RM , et al: Glutamine metabolism by endotoxin-injured lung. J Trauma 31:1068-1075, 1991

12.

Ardawi MS , Majzoub MF , Kateilah SM , et al: Maximal activity of phosphate-dependent glutaminase and glutamine metabolism in septic rats. J Lab Clin Med 118:26-32, 1991

13.

Adrawi MS : Hepatic glutamine metabolism in the septic rat. Clin Science 82:709-716,1992

14.

Austgen TR , Chakrabarti R. , Chen MM , et al: Adaptive regulation in skeletal muscle glutamine metabolism in endotoxin-treated rats. J Trauma 32:600-607. 1992

15.

Inoue Y. Pacitti AJ Souba WW : Endotoxin increases hepatic glutamine transport activity. J Surg Res 54:39.3-400. 1993

16.

Ardawi MS : Effect of glutamine-enriched total parenteral nutrition on septic rats. Clin Science 81:215-222, 1991

17.

Ardawi MS : Effects of xylitol- and/or glutamine-supplemented parenteral nutrition on septic rats. Clin Sci 82:-119-427. 1992

18.

Adrawi MS : Effect of glutamine-supplemented total parenteral nutrition on the small bowel of septic rats. Clin Nutr 11:207-215. 1992

19.

Yoshida S. , Leskiw MJ , Schluter MD , et al: Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats. Am J Physiol 263:E368-373, 1992

20.

Inoue Y. , Grant JP , Snyder PJ : Effect of glutamine-supplemented intravenous nutrition on survival after Escherichia coli-induced peritonitis. JPEN 17:41-46, 1993

21.

Fink MP , Heard SO : Laboratory models of sepsis and septic shock. J Surg Res 49:186-196, 1990

22.

Alexander JW , Gonce SJ , Miskell PW , et al: A new model for studying nutrition in peritonitis. The adverse effect of overfeeding. Ann Surg 209:334-340, 1989

23.

Furst P. , Albers S. , Stehle P. : Glutamine-containing dipeptides in parenteral nutrition. JPEN 14:1185-1245, 1990

24.

Picou D. , Taylor-Roberts T. : The measurement of total protein synthesis and catabolism and nitrogen turnover in infants in different nutritional states and receiving different amounts of dietary protein. Clin Sci 36:283-296, 1969

25.

Garlick PJ , Millward DJ , James WP : The diurnal response of muscle and liver protein synthesis in vivo in meal-fed rats. Biochem J 136:935-945. 1973

26.

Long CL Nelson KM DiRienzo DB , et al: Glutamine supplementation of enteral nutrition: Impact on whole body protein kinetics and glucose metabolism in critically ill patients. JPEN 19:470-476. 1995

27.

Hammarqvist F. Wernerman J. von der Decken A. et al: Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle. Ann Surg 212:637-644. 1990

28.

Jepson MM Bates PC Broadbent P. et al: Relationship between glutamine concentration and protein synthesis in rat skeletal muscle. Am J Physiol 255:E166-172, 1988

29.

Rennie MJ , Hundal HS Babij P. , et al: Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection, and chronic disease. Lancet 2:1008-1012, 1986

30.

Vente JP , Von Meyenfeldt M. , Van Eijk HMH , et al: Plasma-amino acid profiles in sepsis and stress. Ann Surg 209:57-62, 1989

31.

Robinson MK , Kobayashi T. , Rounds JD , et al: Glutamine enhances hepatocellular energetics during sepsis. Surg Forum 43:171-174, 1992

32.

Ogle CK , Ogle JD , Mao JX , et al: Effect of glutamine on phagocytosis and bacterial killing by normal and pediatric burn patient neutrophils. JPEN 18:128-133, 1994

33.

Schroder J. , Wardelmann E. , Winkler W. , et al: Glutamine dipeptide-supplemented parenteral nutrition reverses gut atrophy, disaccharidase enzyme activity, and absorption in rats. JPEN 19:502-506, 1995

34.

Burke DJ , Alverdy JC , Aoys E. , et al: Glutamine-supplemented total parenteral nutrition improves gut immune function. Arch Surg 124:1396-1399, 1989