E. Vinnars

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.

Twenty-two patients undergoing elective abdominal surgery were given total parenteral nutrition (TPN) after the operation. The TPN contained either a conventional amino acid solution supplemented with glutamine or a conventional amino acid solution without supplementation. To study amino acid and protein metabolism, muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decrease in the intracellular concentration of free glutamine was less pronounced in the glutamine group (21.8 +/- 5.5%) than in the control group (38.7 +/- 5.1%; p less than 0.05). The protein synthesis was reflected in the concentration and size distribution of ribosomes. No significant changes in these parameters were seen in the glutamine group after the operation. In the control group, the total concentration of ribosomes fell by 27.2 +/- 8.5% (p less than 0.05), and the relative proportion of polyribosomes fell by 10.6 +/- 2.9% (p less than 0.01). Although there were significant changes in the control group, no significant differences in the changes of these parameters between the two groups were detected. The cumulative nitrogen loss was significantly less in the glutamine group as compared to the control group during the period studied--2.3 +/- 1.4 g versus 8.5 +/- 1.5 g, respectively (p less than 0.01). Administration of glutamine to catabolic patients is advocated.

Biosynthetic human growth hormone preserves both muscle protein synthesis and the decrease in muscle-free glutamine, and improves whole-body nitrogen economy after operation.

As a reproducible human trauma model, patients (n = 17) undergoing elective cholecystectomy were studied for 3 postoperative days. They were randomly allocated to receive either recombinant human growth hormone (hGH; 0.3 U/kg/24 hours) or placebo together with total parenteral nutrition, including 0.2 gN/kg/24 hours and 135 kJ/kg/24 hours. Before operation and on the third postoperative day, percutaneous muscle biopsies were performed to determine the concentration and size distribution of ribosomes and the free amino acid concentrations. The significant postoperative decrease in the total ribosome concentration (15.3 ± 6.4%) and the polyribosome concentration (20.9 ± 6.5%) in the control group was impeded in the group receiving synthetic hGH. Muscle free glutamine decreased by 35.6 ± 4.2% in the control group and to a lesser extent in the group that was given hGH after operation (p < 0.05). The protein content of skeletal muscle was unchanged. The cumulated nitrogen balance for the study period was negative in the control group (-7.09 ± 0.71 gN), but was not different from zero in the hGH group (-2.32 ± 1.66 gN). It is concluded that synthetic hGH administered after operation has beneficial effects on the whole-body nitrogen economy, as indicated by the unchanged capacity for protein synthesis in skeletal muscle, the preserved levels of muscle free glutamine, and improvement in the whole-body nitrogen balance. The effects of hGH on skeletal muscle protein and amino acid metabolism can explain the postoperative nitrogen-sparing effect attributed to hGH.

α-ketoglutarate and postoperative muscle catabolism

The hypothesis that muscle protein catabolism after trauma is associated with a shortage of alpha-ketoglutarate, rather than glutamine, was tested. Addition of alpha-ketoglutarate to postoperative total parenteral nutrition prevented the decrease in muscle protein synthesis and free glutamine that usually occurs after surgery. alpha-ketoglutarate supplementation may improve recovery after trauma.

Alanyl-glutamine counteracts the depletion of free glutamine and the postoperative decline in protein synthesis in skeletal muscle.

Skeletal muscle protein and amino acid metabolism change after surgical trauma during a period characterized by skeletal muscle protein catabolism. Available total parenteral nutrition (TPN) not containing glutamine does not prevent these changes, while TPN enriched with glutamine has been shown to have beneficial effects on postoperative skeletal muscle protein metabolism. Glutamine, in the form of a dipeptide, alanyl-glutamine, was added to TPN. Patients undergoing elective cholecystectomy were given postoperative TPN. Two groups received isocaloric and isonitrogenous conventional TPN, one group with (n = 8) and the other without an addition of alanyl-glutamine (n = 8). Skeletal muscle protein metabolism was studied in muscle biopsy specimens from which the muscle free amino acid pattern and the concentration and size distribution of ribosomes, serving as a measure of protein synthesis, were determined. In the control group, muscle free glutamine decreased by 38.8% +/- 6.6% and the polyribosome concentration per mg of DNA decreased by 21% +/- 5.2% after operation. In the group given TPN supplemented with alanyl-glutamine, these two parameters of muscle protein and amino acid metabolism did not change significantly. Compared to the control group, whole-body nitrogen balance was improved after operation by the addition of alanyl-glutamine to TPN (p less than 0.01). Muscle free glutamine and muscle protein synthesis were preserved after operation and the whole-body nitrogen balance was improved by adding glutamine in the form of alanyl-glutamine to TPN. The dipeptide alanyl-glutamine seems to be a suitable means of providing glutamine in a stable form.

Role of Glutamine and Its Analogs in Posttraumatic Muscle Protein and Amino Acid Metabolism

Skeletal muscle protein catabolism following trauma has until recently not been possible to counteract by intravenous nutritional means. The obligatory loss of nitrogen with concomitant reduction of skeletal muscle protein synthesis is also accompanied by a decrease of muscle free glutamine, the extent of which is proportional to the muscle protein catabolism. Serving as a human model of surgical trauma, patients undergoing elective cholecystectomy were given total parenteral nutrition including additions of either glutamine or its analogs (ornithine-alpha-ketoglutarate, alpha-ketoglutarate, or alanylglutamine) during 3 postoperative days. The polyribosome concentration and the intracellular glutamine concentration in skeletal muscle, as well as nitrogen balance, showed a less pronounced skeletal muscle catabolism in these groups than when conventional total parenteral nutrition was given. It is concluded that a support of either glutamine or its carbon skeleton, alpha-ketoglutarate, counteracts the postoperative fall of muscle free glutamine and of muscle protein synthesis. Furthermore, statistical correlations could be shown between the changes of muscle glutamine and muscle protein synthesis and the postoperative nitrogen losses.

Ornithine-alpha-ketoglutarate improves skeletal muscle protein synthesis as assessed by ribosome analysis and nitrogen use after surgery.

Total parenteral nutrition (TPN) was given for 3 days after elective abdominal surgery. The control group (N = 9) received TPN only and one group of patients (N = 6) received TPN supplemented with ornithine-alpha-ketoglutarate (0.35 g/kg bw/day). Protein synthesis in skeletal muscle was assessed from the total ribosome concentration and the percentage of polyribosomes. In the control group the total concentration of ribosomes decreased after surgery by 23% (p less than 0.05) and the percentage of polyribosomes decreased by 21% (p less than 0.01), whereas in the ornithine-alpha-ketoglutarate group both variables remained unaffected. The cumulative urinary urea excretion was significantly larger in the control group than in the ornithine-alpha-ketoglutarate group (p less than 0.05). The calculated nitrogen balance was negative in the control group on each day of the study (p less than 0.05), but that of the ornithine-alpha-ketoglutarate group was not statistically different from zero. The results show that postoperative maintenance of muscle protein synthesis and a more effective nitrogen use was achieved by supplementing TPN with ornithine-alpha-ketoglutarate, 0.35 g/kg bw/day.

The effects of branched chain amino-acids upon postoperative muscle protein synthesis and nitrogen balance

Abstract Patients undergoing elective cholecystectomy were given total parenteral nutrition containing adequate amounts of calories and nitrogen postoperatively. One group (n=8) received a solution enriched with branched chain amino-acids (BCAA) and a control group (n=9) was given a balanced amino-acid solution. Muscle biopsy specimens were taken before surgery and on the third postoperative day. Muscle protein synthesis was assessed by comparing the concentration and size distribution of ribosomes between these two occasions. The total ribosome concentration per mg of DNA was decreased by 24% postoperatively at 3 days in both groups as compared with the preoperative value (p

The diurnal pattern of protein synthesis in human skeletal muscle

The diurnal pattern of protein synthesis in skeletal muscle was studied in relation to the serum concentrations of glucose, insulin and cortisol. Twelve healthy volunteers were given an ordinary hospital diet at 4-hourly intervals. The concentration of insulin showed peaks in response to food intake, and that of cortisol decreased over the day. Muscle biopsies were taken 30 min before the first food intake and 1.5 or 3.5 h after a meal. Irrespective of the time intervals after food intake, the total ribosome concentration, percentage amount of polyribosomes and polyribosome concentrations remained unaltered, indicating that there were no alterations in the capacity for protein synthesis accompanying the feeding schedule. The results suggest that a muscle sample taken in the morning after an overnight fast is representative of the protein synthesis during the day as assessed by the ribosome concentration and the size distribution of ribosomes.

The Interpretation of Ribosome Determinations to Assess Protein Synthesis in Human Skeletal Muscle

A survey is given on the determination and interpretation of ribosomal concentration and size distribution in animal and human muscle biopsy samples as a means to assess protein synthesis under various physiological and pathological conditions.