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F Hammarqvist

Publications and source records attributed to F Hammarqvist.

11 recordsLinked to original sources

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 less than 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.

Adult

Alpha-ketoglutarate preserves protein synthesis and free glutamine in skeletal muscle after surgery.

Serving as a reproducible human trauma model, patients (n = 21) undergoing elective cholecystectomy received postoperative total parenteral nutrition with (n = 9) or without (n = 12) alpha-ketoglutarate (AKG) supplementation. Skeletal muscle biopsy specimens were taken before surgery and on the third postoperative day. The postoperative decreases in the concentrations of free glutamine and basic amino acids seen in the control group were counteracted in the AKG group (p less than 0.05). Muscle protein synthesis was estimated by ribosome analysis. On the third postoperative day the control group showed a decline in the polyribosome concentration (25.8% +/- 4.5%; p less than 0.001). No significant change was observed in the AKG group. On each postoperative day the nitrogen balance was negative in the control group but not in the AKG group. In the control group the cumulative nitrogen balance amounted to -9.9 +/- 1.8 gm of nitrogen and in the AKG group -2.6 +/- 2.6 gm of nitrogen, which was significantly different (p less than 0.05). Administration of AKG, the carbon skeleton corresponding to glutamine, produced results similar to those seen when glutamine is added to postoperative total parental nutrition. The results suggest that the availability of precursors for glutamine synthesis in skeletal muscle is crucial for the degree of muscle protein catabolism after surgical trauma.

Adult

Alpha-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.

Cholecystectomy

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.

Patients undergoing elective cholecystectomy provide a highly reproducible model of the effects of trauma on intermediary metabolism. Three parenteral nutrition regimens were given to groups of eight such patients. An isonitrogenous total parenteral nutrition, including a commercially available amino acid solution, an amino acid solution enriched with branched chain amino acids or one supplemented with ornithine-alpha-ketoglutarate, was given after operation. The intra cellular free amino acid concentrations of skeletal muscle were determined in tissue specimens obtained before operation and on the third postoperative day using a percutaneous needle biopsy technique. The mean (s.e.m.) decrease in the concentrations of free intracellular glutamine on the third postoperative day was less pronounced (P less than 0.05) in the ornithine-alpha-ketoglutarate group (18.8(7.5)per cent) than in the control group (39.4(5.1)per cent) or the branched chain amino acid group (45.3(6.1)per cent). In conclusion, in the immediate postoperative period total parenteral nutrition supplemented with ornithine-alpha-ketoglutarate countered the decline in the muscle free glutamine. No difference in this parameter was seen between the control group and the branched chain amino acid group.

Amino Acids

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.

Cholecystectomy

Stress hormones given to healthy volunteers alter the concentration and configuration of ribosomes in skeletal muscle, reflecting changes in protein synthesis.

1. The influence of elevated concentrations of stress hormones on the concentration of ribosomes and the relative proportion of polyribosomes, reflecting protein synthesis in vivo, in human skeletal muscle was investigated. Healthy volunteers were given a 6 h infusion of adrenaline (n = 8), cortisol (n = 8), a triple-hormone combination of adrenaline, cortisol and glucagon (n = 8), or saline (n = 8). 2. The total ribosome concentration declined by 30.4 +/- 7.2% in the triple-hormone group (P less than 0.01), by 26.9 +/- 8.6% in the cortisol group (P less than 0.05) and by 24.8 +/- 11.2% in the adrenaline group (P less than 0.05). The proportion of polyribosomes to total ribosomes decreased by 8.5 +/- 2.2% in the triple-hormone group (P less than 0.05). 3. During hormone infusion the serum glucose levels were enhanced. The insulin concentrations in serum were elevated in the adrenaline group and the triple-hormone group, but not in the cortisol group. Serum insulin decreased in the control group. 4. The results indicate an effect of the combined stress hormone infusion on the total ribosome concentration as well as on the relative abundance of polyribosomes. The single hormones influenced the total ribosome concentration only. The results suggest a critical role for stress hormones in producing the decline in muscle protein synthesis seen after trauma.

Adult

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.

Cholecystectomy

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.

Amino Acids