Original Communications| Volume 129, ISSUE 5, P576-586, May 2001

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Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma


      Background. Muscle protein catabolism, reflected by a decrease in glutamine (GLN), a decrease in muscle protein synthesis, and a negative nitrogen balance can be reduced by either administration of GLN or growth hormone (GH). In this study, the effects of a combination of GH and GLH were studied. Methods. Patients (n = 16) undergoing abdominal operation were given total parenteral nutrition (TPN) containing either GLN alone or GLN together with GH (GH/GLN) during 3 postoperative days. The amino acid concentration and protein synthesis in muscle tissue and the nitrogen balance were measured. Results. GH/GLN reduced nitrogen losses compared with GLN alone (−5.8 ± 1.4 g nitrogen versus −10.6 ± 1.1 g nitrogen, P <.05). GH/GLN maintained muscle GLN at preoperative levels compared with a 47.5% ± 6.3% decline in the GLN group. A similar decrease was seen in the fractional synthesis rate of muscle protein postoperatively in both groups. Conclusions. GH has an additive effect given together with GLN on muscle amino acid metabolism, preventing the decrease in the GLN concentration in skeletal muscle and diminishing the loss of whole body nitrogen. However, the improvements in muscle amino acid concentrations and nitrogen loss were not associated with differences between the groups in muscle protein synthesis postoperatively. (Surgery 2001;129:576-86.)
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        • Gamrin L
        • Essén P
        • Hultman E
        • Wernerman J
        A descriptive study of skeletal muscle metabolism in critically ill patients: free amino acids, energy rich phosphates, protein, nucleic acids, fat, water and electrolytes.
        Crit Care Med. 1996; 24: 575-583
        • Jones C
        • Hussey RM
        • Griffiths RD
        A tool to measure the change in health status of selected adult patients before and after intensive care.
        Clin Intensive Care. 1993; 4: 160-165
        • Clowes Jr, GH
        • Randell HT
        • Cha CJ
        Amino acid and energy metabolism in septic and traumatized patients.
        JPEN J Parenter Enteral Nutr. 1980; 4: 195-205
        • Christensen T
        • Bendix T
        • Kehlet H
        Fatigue and cardiorespiratory function following abdominal surgery.
        Br J Surg. 1982; 69: 417-419
        • Windsor JA
        • Hill GL
        Risk factors for postoperative pneumonia: the importance of protein depletion.
        Ann Surg. 1988; 208: 209-214
        • Newsholme EA
        Metabolic control logic applied to glutamine flux between muscle and the immune system.
        Clin Nutr. 1990; 9: 113-114
        • Superina R
        • Meakins JL
        Delayed hypersensitivity, anergy and the surgical patient.
        J Surg Res. 1984; 37: 151-174
        • Ek AC
        • Larsson J
        • von Schenk H
        • Thorslund S
        • Unosson M
        • Bjurulf P
        The correlation between anergy, malnutrition, and clinical outcome in an elderly hospital population.
        Clin Nutr. 1990; 9: 185-189
        • Vinnars E
        • Bergström J
        • Fürst P
        Influence of the postoperative state on the intracellular free amino acids in human muscle tissue.
        Ann Surg. 1975; 182: 665-671
        • Essén P
        • McNurlan MA
        • Wernerman J
        • Vinnars E
        • Garlick PJ
        Uncomplicated surgery, but not general anesthesia, decreases muscle protein synthesis.
        Am J Physiol. 1992; 262: E253-E260
        • Wernerman J
        • von der Decken A
        • Vinnars E
        Protein synthesis in skeletal muscle in relation to nitrogen balance after abdominal surgery. The effect of total parenteral nutrition.
        JPEN J Parenter Enteral Nutr. 1986; 10: 578-582
        • O'Keefe SJD
        • Sender PM
        • James WPT
        “Catabolic” loss of body nitrogen in response to surgery.
        Lancet. 1974; 2: 1035-1038
        • Aulick LH
        • Wilmore DW
        Increased peripheral amino acid release following burn injury.
        Surgery. 1979; 85: 560-565
        • Wilmore DW
        • Smith RJ
        • O'Dwyer ST
        • Jacobs DO
        • Ziegler TR
        • Wang X-D
        The gut: a central organ after surgical stress.
        Surgery. 1988; 104: 917-923
        • Souba W
        • Klimberg S
        • Plumley D
        • Salloum RM
        • Flynn TC
        • Bland KI
        • et al.
        The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection.
        J Surg Res. 1990; 48: 383-391
        • Vinnars E
        • Holmström B
        • Schildt B
        • Odebäck A-C
        • Fürst P
        Metabolic effects of four intravenous nutritional regimens in patients undergoing elective surgery. II: Muscle amino acids and energy-rich phosphates.
        Clin Nutr. 1983; 2: 3-11
        • Stehle P
        • Mertes N
        • Puchstein C
        • Zander J
        • Albers S
        • Lawin P
        Effect of parenteral glutamine peptide supplements on muscle glutamine loss and nitrogen balance after major surgery.
        Lancet. 1989; 1: 231-233
        • Hammarqvist F
        • Wernerman J
        • Ali MR
        • von der Decken A
        • Vinnars E
        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. 1989; 209: 455-461
        • Hammarqvist F
        • Wernerman J
        • von der Decken A
        • Vinnars E
        Alanyl-glutamine counteracts the depletion of free glutamine and the decline in protein synthesis postoperatively in skeletal muscle.
        Ann Surg. 1990; 212: 637-644
        • Vinnars E
        • Hammarqvist F
        • von der Decken A
        • Wernerman J
        The role of glutamine and its analogues in posttraumatic muscle protein and amino acid metabolism.
        JPEN J Parenter Enteral Nutr. 1990; 14: 125S-9
        • Mjaaland M
        • Unneberg K
        • Larsson J
        • Nilsson L
        • Revhaug A
        Growth hormone after abdominal surgery attenuated forearm glutamine, alanine, 3-methylhistidine, and total amino acid efflux in patients receiving total parenteral nutrition.
        Ann Surg. 1993; 217: 413-422
        • Hammarqvist F
        • Strömberg C
        • von der Decken A
        • Vinnars E
        • Wernerman J
        Biosynthetic human growth hormone preserves both muscle protein synthesis, the decrease in muscle free glutamine and improves whole body nitrogen economy postoperatively.
        Ann Surg. 1992; 216: 184-191
        • Unneberg K
        • Mjaaland M
        • Balteskard L
        • Jenssen TG
        • Bj°ro T
        • Revhaug A
        Both growth hormone and exogenous glutamine increase gastrointestinal glutamine uptake in trauma.
        Ann Surg. 1997; 225: 97-102
        • Barle H
        • Nyberg B
        • Andersson K
        • et al.
        Growth hormone stimulates albumin synthesis in man.
        Clin Nutr. 1997; 16: O.23
        • Takala J
        • Ruokonen E
        • Webster NR
        • Nielsen MS
        • Zandstra DF
        • Vundelinckx G
        • et al.
        Increased mortality associated with growth hormone treatment in critically ill adults.
        N Engl J Med. 1999; 341: 785-792
        • McNurlan M
        • Essén P
        • Thorell A
        • Calder AG
        • Anderson SE
        • Ljungqvist O
        • et al.
        Response of protein synthesis in human skeletal muscle to insulin: an investigation with l [2H5] phenylalanine.
        Am J Physiol. 1994; 267: 102-108
        • Calder AG
        • Anderson SE
        • Grant I
        • McNurlan MA
        • Garlick PJ
        The determination of low d5-phenylalanine enrichment (0.002-0.09) atom percent excess, after conversion to phenylethylamine, in relation to protein turnover studies by gas chromatography mass spectrometry.
        Rapid Commun Mass Spectrom. 1992; 6: 421-424
        • Hammarqvist F
        • Wernerman J
        • Ali MR
        • Vinnars E
        Effects of an amino acid solution enriched with either branched chain amino acids or ornithine-alpha-ketoglutarate on the postoperative intracellular amino acid concentration of skeletal muscle.
        Br J Surg. 1990; 77: 214-218
        • Wernerman J
        • von der Decken A
        • Vinnars E
        Size distribution of ribosomes in biopsy specimens of human skeletal muscle during starvation.
        Metabolism. 1985; 34: 665-669
        • Snedecor GW
        • Cochran WG
        Statistical methods.
        in: 7th ed. : Iowa State University Press, Ames (Iowa)1980: 141-143
        • Hammarqvist F
        • Wernerman J
        • von der Decken A
        • Vinnars E
        An addition of alpha-ketoglutarate to total parenteral nutrition given following elective abdominal surgery improves nitrogen balance, counteracts the fall in protein synthesis, and spares intracellular free glutamine in skeletal muscle.
        Surgery. 1991; 109: 28-36
        • Luo J-L
        • Hammarqvist F
        • Andersson K
        • Wernerman J
        Skeletal muscle glutathione after surgical trauma.
        Ann Surg. 1996; 223: 420-427
        • Palmer TE
        • Griffiths RD
        • Jones C
        Effect of parenteral l-glutamine on muscle in the very severely ill.
        Nutrition. 1996; 12: 316-320
        • Mittendorfer B
        • Core DC
        • Herndon DN
        • Wolfe RR
        Accelerated glutamine synthesis in critically ill patients cannot maintain normal intramuscular free glutamine concentration.
        JPEN J Parenter Enteral Nutr. 1999; 23: 243-252
        • Ziegler TR
        • Young LS
        • Benfell K
        • Scheltinga M
        • Hortos K
        • Bye R
        • et al.
        Clinical and metabolic efficacy of glutamine-supplemented parenteral nutrition after bone marrow transplantation. A randomized, double-blind, controlled study.
        Ann Intern Med. 1992; 116: 821-828
        • Schloerb PR
        • Amare M
        Total parenteral nutrition with glutamine in bone marrow transplantation and other clinical applications: a randomized, double blind study.
        JPEN J Parenter Enteral Nutr. 1993; 17: 407-413
        • Griffiths RD
        • Jones C
        • Palmer A
        Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition.
        Nutrition. 1997; 13: 295-302
        • Neu J
        • Roig JC
        • Meetze WH
        • Veerman M
        • Carter C
        • Millsaps M
        • et al.
        Enteral glutamine supplementation for very low birth weight infants decreases morbidity.
        J Pediatr. 1997; 131: 691-699
        • Houdijk APJ
        • Rijnsburger ER
        • Jansen J
        • Wesdorp RI
        • Weiss JK
        • McCamish MA
        • et al.
        Randomised trial of glutamine-enriched enteral nutrition on infectious morbidity in patients with multiple trauma.
        Lancet. 1998; 352: 772-776
        • Ponting GA
        • Halliday D
        • Teale JD
        • Sim AJW
        Postoperative positive nitrogen balance with intravenous hyponutrition and growth hormone.
        Lancet. 1988; 1: 438-440
        • Soroff HS
        • Pearson E
        • Green NL
        • Artz CP
        The effect of growth hormone on nitrogen balance at various levels of intake in burned patients.
        Surg Gynecol Obstet. 1960; 111: 259-273
        • Essén P
        • McNurlan MA
        • Sonnenfeld T
        • Milne E
        • Vinnars E
        • Wernerman J
        • et al.
        Muscle protein synthesis after operation: effects of intravenous nutrition.
        Eur J Surg. 1993; 159: 195-200
        • Hammarqvist F
        Intravenous amino acid supply after trauma: the effects of glutamine on muscle protein metabolism [thesis].
        Karolinska Institute, Stockholm, Sweden1989
        • Salzman PN
        • Eagle H
        • Sebring ED
        The utilization of glutamine, glutamic acid, and ammonia for the biosynthesis of nucleic acid bases in mammalian cell cultures.
        J Biol Chem. 1958; 230: 1001-1012
        • Häussinger D
        • Lang F
        • Bauers K
        • Gerok W
        Interactions between glutamine metabolism and cell-volume regulation in perfused rat liver.
        Eur J Biochem. 1990; 188: 689-695
        • Hermansson M
        • Wickelgren R
        • Hammarqvist F
        • Bjarnason R
        • Wennstrom I
        • Wernerman J
        • et al.
        Measurement of human growth hormone receptor messenger ribonucleic acid by a quantitative polymerase chain reaction-based assay: demonstration or reduced expression after elective surgery.
        J Clin Endocrinol Metab. 1997; 82: 421-428
        • Bjarnason R
        • Wickelgren R
        • Hermansson M
        • Hammarqvist F
        • Carlsson B
        • Carlsson LM
        Growth hormone treatment prevents the decrease in insulin-like growth factor I gene expression in patients undergoing abdominal surgery.
        J Clin Endocrinol Metab. 1998; 83: 1566-1572
        • Unneberg K
        • Balteskard L
        • Mjaaland M
        • Revhaug A
        Growth hormone impaired compensation of hemorrhagic shock after trauma and sepsis in swine.
        J Trauma. 1996; 41: 775-780
        • Petersen SR
        • Holaday NJ
        • Jeevanandam M
        Enhancement of protein synthesis efficiency in parenterally fed trauma victims by adjuvant recombinant human growth hormone.
        J Trauma. 1994; 36: 726-733
        • Fleming RY
        • Rutan RL
        • Jahoor F
        • Barrow RE
        • Wolfe RR
        • Herndon DN
        Effect of recombinant growth hormone on catabolic hormones and free fatty acids following thermal injury.
        J Trauma. 1992; 32: 698-703
        • Roth E
        • Valentini L
        • Semsroth M
        • Holzenbein T
        • Winkler S
        • Blum WF
        • et al.
        Resistance of nitrogen metabolism to growth hormone treatment in the early phase after injury of patients with multiple injuries.
        J Trauma. 1995; 38: 136-141
        • Matsuda T
        • Saito H
        • Inoue T
        • Fukatsu K
        • Han I
        • Furukawa S
        • et al.
        Growth hormone inhibits apoptosis and up-regulates reactive oxygen intermediates production by human polymorphonuclear neutrophils.
        JPEN J Parenter Enteral Nutr. 1998; 22: 368-374