Metabolism and nutrition in trauma.
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Energy Metabolism↗
Biomedical subjects
J Wernerman
Publications and source records attributed to J Wernerman.
Enzymatic capacity and protein synthesis in human muscle postoperatively.
The glycolytic and aerobic oxidative capacity in skeletal muscle was investigated to reveal if the decrease seen in muscle protein synthesis is accompanied by a fall in the enzymatic capacity to oxidize substrates. Six patients undergoing elective abdominal surgery were investigated by percutaneous muscle biopsies taken before surgery and on the first and third postoperative days. Protein synthesis as assessed by the polyribosome concentration was 40% lower on the third day postoperatively than before surgery (p less than 0.01). The glycolytic and oxidative capacity was evaluated by determining the activity of eight key enzymes in the intracellular oxidative metabolism, namely total creatine kinase (CK), the isozymes CK-MB and mitochondrial CK, lactate dehydrogenase, citrate synthase, aspartate aminotransferase, and phosphofructokinase, and also the concentration of myoglobin. None of these parameters were affected in the immediate postoperative period independently of the provision of nutritional support. It was concluded that the decrease in protein synthesis is not accompanied by a concomitant decline in the enzymatic oxidative capacity in skeletal muscle in the period immediately following elective surgery.
Adult↗
Protein synthesis in skeletal muscle of rats following starvation and refeeding.
Determination of protein synthesis in individual tissues is important to understand the changes in protein metabolism during catabolic states. Three methods based on different underlying assumptions were compared in assessing muscle protein synthesis during nutritional manipulation. Rats were nonstarved, starved for 1 or 3 days, or refed for 2 days after 3 days of starvation. The extensor digitorum longus (EDL) muscles from the two hindlegs were used for analysis. In one EDL muscle the concentration and size distribution of ribosomes as well as the incorporation of [14C]leucine into protein in a cell-free system were determined. The other EDL muscle was incubated as such and the incorporation of [14C]phenylalanine into protein was measured. The total ribosome concentration per milligram of DNA decreased to 65% on the third day of starvation and remained low after refeeding. The amount of polyribosomes in the percentage of total ribosomes fell to 90% on the first day of starvation, regained the initial level on the third day, and reached 110% upon refeeding. During refeeding amino acid incorporation into protein in a cell-free system decreased to 40% and that in intact muscle to 64% of the prestarvation level. Upon refeeding, the activity increased to or above the original values. The use of several different techniques in parallel to assess protein synthesis in skeletal muscle is recommended since it gives information about the factors involved in regulation of the translational process in intact mammalian tissues.
Animals↗
The effect of trauma and surgery on interorgan fluxes of amino acids in man.
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Amino Acids↗
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.
Cholecystectomy↗
Polyribosome concentration in human skeletal muscle after starvation and parenteral or enteral refeeding.
Posttraumatic and septic states cause a loss of body proteins resulting in a negative nitrogen balance. The major part of the excreted nitrogen is derived from the proteins of skeletal muscle. The loss in proteins is due to a decrease in protein synthesis rather than an increase in protein degradation. Nutritional support may increase protein synthesis, and determination of its activity in skeletal muscle will give information on the utilization of nutrients in catabolic patients. The effect of nutritional support on healthy subjects was studied to achieve a background for future clinical studies. Male volunteers between 20 and 40 years old were refed parenterally or enterally after three days of starvation. Muscle biopsies (50 mg) were analyzed for the size distribution of ribosomes in a sucrose density gradient, and the ribosome concentration was determined per mg of DNA. Changes in the percentage content of polyribosomes preceded those of the total ribosome concentration. The total polyribosome concentration per gram wet weight of skeletal muscle decreased significantly during starvation. After one and two days of refeeding, a significant increase was observed, but the original level of the nonstarved subjects was not reached. The total ribosome concentration increased upon refeeding, but was not significantly different from that of the starved condition. The nitrogen balance was negative during starvation but attained equilibrium after two days of refeeding. Nutrition administered by the parenteral or enteral route were equally effective in restoring protein synthesis.
3-Hydroxybutyric Acid↗
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.
Amino Acids↗
Size distribution of ribosomes in biopsy specimens of human skeletal muscle during starvation.
The changes in the poly- and monoribosome distribution and in the total ribosome concentration in muscle during short term starvation were investigated. Transcutaneous muscle biopsies of 50 mg wet wt were taken from healthy human subjects, nonstarved and after one, two, and three days of total starvation. The percentage amount of polyribosomes was significantly lower (P less than 0.02) on days 2 and 3 of starvation than on day 0 (nonstarved). No significant sex-dependent differences were observed between the group of five females and six males. Ribosome concentration per g wet wt of muscle tissue was significantly lower on day 3 than on each preceding day (P less than 0.05). The reproducibility of the polyribosome analyses, together with the changes observed, suggest a future application of this method for evaluation of the effects of nutritional support in patients with posttraumatic and septic conditions.
Acetoacetates↗
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.
Journal Article↗
The effect of stress hormones on the interorgan flux of amino acids and on the concentration of free amino acids in skeletal muscle.
Plasma concentrations of free amino acids have previously been found to decrease posttraumatically and this decrease can be reproduced by infusion of stress hormones. The mechanisms underlying this effect has not been investigated and therefore 14 healthy subjects were studied by infusing adrenaline alone or a combination of adrenaline, glucagon, and cortisol, in dosages giving pathophysiological plasma concentrations of the hormones. The influence on the interorgan fluxes of free amino acids and on the concentrations of free amino acids in skeletal muscle were determined. During hormone infusion splanchnic oxygen consumption doubled, indicating an increase in metabolic activity. There was a significant decrease in the arterial plasma level of all amino acids except alanine. Significant increases in alanine flux was noted, the release from one leg doubled and the splanchnic uptake increased by 60%. After only 1 h all essential amino acids showed a significantly decreased concentration in muscle while the level of alanine was increased. There were no differences between the two hormone groups. The results indicate that stress hormones can initiate an increased formation of alanine in skeletal muscle and an increase in alanine transport from the periphery to the splanchnic area.
Journal Article↗
Protein synthesis in skeletal muscle in relation to nitrogen balance after abdominal surgery: the effect of total parenteral nutrition.
Protein synthesis in skeletal muscle was studied in patients after elective abdominal surgery, using the concentration and size distribution of ribosomes. The patients were given either an electrolyte solution or total parenteral nutrition postoperatively. The analyses were performed on muscle biopsy specimens taken prior to surgery and on days 1 and 3 following surgery. The percentage content of polyribosomes, total ribosome concentration and the polyribosome concentrations per milligram of tissue DNA were determined. Elective abdominal surgery caused a significant decrease (p less than 0.05) in the three variables. Total parenteral nutrition did not prevent the decrease. The negative nitrogen balance was significantly improved by total parenteral nutrition, but it did not reach equilibrium. The results show that total parenteral nutrition given postoperatively did not maintain protein synthesis activity in skeletal muscle. The improvement in nitrogen balance suggests that amino acids are utilized by tissues other than skeletal muscle.
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↗
Long-term effect of glycyl-glutamine after elective surgery on free amino acids in muscle.
In order to evaluate the long-term effect of total parenteral nutrition supplemented with glutamine after surgery, patients (n = 17) undergoing elective abdominal surgery were randomized into two groups and studied for 30 days after surgery. During the 3 days immediately after surgery, one group (n = 8) was given total parenteral nutrition including a conventional amino acid solution (control group). The other group (n = 9) was given isocaloric and isonitrogenous total parenteral nutrition including the same amino acid solution supplemented with the dipeptide, glycyl-glutamine (GLN group). Oral food intake started on the third postoperative day and was gradually increased at will. The concentration of free amino acids in percutaneous muscle biopsy specimens was determined preoperatively and on days 3, 10, 20, and 30 after the operation. Free glutamine decreased in skeletal muscle in the control group on days 3 and 10 by 32.2 +/- 5.4% (p < .01) and 20.1 +/- 6.9% (p < .05), respectively. In the glycyl-glutamine group, the decrease in glutamine was delayed until day 10 when it was 22.1 +/- 8.1% (p < .05). The glutamine levels were restored on days 20 and 30 in both groups. Total parenteral nutrition supplemented with glutamine maintained the free glutamine levels in skeletal muscle after surgery, but when treatment was discontinued, the glutamine concentration in muscle dropped, despite a normal enteral dietary intake.
Amino Acids↗
Intestinal amino acid content in critically ill patients.
BACKGROUND: The purpose of the study was to determine the concentrations of free amino acids and the total protein content of the human intestinal mucosa during critical illness. METHODS: The free amino acid and protein concentrations in endoscopically obtained biopsy specimens from the duodenum and the distal colonic segments were determined on 19 critically ill patients. The free amino acids were separated by ion exchange chromatography and detected by fluorescence, and the protein content was quantified by the method of Lowry. RESULTS: In general, the typical amino acid pattern of the intestinal mucosa was seen, with very high levels of taurine, aspartate and glutamic acid. The main difference, as compared to a reference series of healthy subjects, was the elevated glutamine concentration of the duodenal mucosa. This amino acid was unaltered in the descending colon and depressed in the rectum. At the same time, the glutamatic acid concentrations were unaltered, suggesting that the degradation of glutamine was not increased in the septic state of the majority of the patients studied. Phenylalanine and the two branched-chain amino acids, valine and leucine, were elevated in the duodenal mucosa, and in the colonic mucosa, methionine and phenylalanine were elevated; otherwise, all the other individual amino acids were unaltered or depressed. CONCLUSIONS: The alterations seen in mucosal free amino acid and protein concentrations in connection with critical illness are different in many respects and contrast with the findings seen after starvation or moderate surgical trauma.
Adult↗
Muscle protein synthesis rate decreases 24 hours after abdominal surgery irrespective of total parenteral nutrition.
BACKGROUND: Muscle protein synthesis rate is known to decrease postoperatively as a part of the catabolic response to trauma. Conventional total parenteral nutrition (TPN) in the postoperative period does not seem to counteract the decrease in protein synthesis. However, it is still unclear if ongoing TPN given continuously after surgery would inhibit this fall in muscle protein synthesis. METHODS: The rate of protein synthesis in skeletal muscle was determined before and 24 hours after open cholecystectomy, used as a standardized human model of trauma. Patients (n = 14) were randomized to receive either TPN continuously throughout the postoperative period or saline as postoperative fluid therapy. The protein synthesis rate was calculated from the increase in enrichment of labeled phenylalanine in protein after an IV flooding dose of [2H5] phenylalanine, 45 mg/kg body weight. RESULTS: The fractional synthesis rate decreased by 31% from 1.74 +/- 0.13% to 1.15 +/- 0.10% per 24 hours in the saline group (p < .02) and by 23% from 1.59 +/- 0.10% to 1.22 +/- 0.07% per 24 hours in the group receiving TPN (p < .01), showing no significant difference between the two groups. CONCLUSION: A continuous and ongoing infusion of conventional TPN started immediately after surgery did not counteract the obligatory decline of muscle protein synthesis, observed 24 hours postoperatively.
Adult↗
The effects of short-term parenteral nutrition on human liver protein and amino acid metabolism during laparoscopic surgery.
BACKGROUND: This study was undertaken to elucidate the specific effects of short-term artificial nutrition on human liver protein metabolism. METHODS: Thirty patients undergoing elective laparoscopic cholecystectomy were studied: a control group (n = 16) and a group that received total parenteral nutrition (TPN; n = 14). The nutrition consisted of a balanced i.v. solution of nutrients (17.5 nonprotein kcal/kg body wt, 50% fat, 50% carbohydrates, and 0.1 gN/kg) that was discontinued when the investigation was finished, after a total infusion time of 8.6 +/- 1.0 hours. A liver biopsy specimen was taken as soon as possible after surgery was started, for the determination of the free hepatic amino acid concentrations. In 16 of the patients, L[2H5]phenylalanine was given by i.v. to determine the fractional synthesis rate of total liver protein in a second liver biopsy specimen taken approximately 30 minutes later. RESULTS: The fractional synthesis rate of total liver protein was 15.2% +/- 4.7%/d in the TPN group (n = 7), which was not different from that of the control group (17.7% +/- 3.8%/d, n = 9). However, the free hepatic concentrations of alanine (p < .05) and the essential amino acids increased (p < .001) in the TPN group, whereas the total hepatic amino acid concentrations were comparable between the groups. CONCLUSION: Thus short-term TPN induced specific changes of the free hepatic amino acid concentrations, whereas total liver protein synthesis remained unaffected by the nutrition.
Adult↗
Clinical experiences with glutamine supplementation.
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Glutamine↗