Erik Vinnars

Glutamine and ornithine-α-ketoglutarate but not branched-chain amino acids reduce the loss of muscle glutamine after surgical trauma

The concentration of free glutamine in skeletal muscle decreases characteristically after surgical trauma. In animal studies a correlation between muscle protein synthesis and the glutamine concentration is reported. For pharmaceutical reasons, commercially available amino acid solutions do not contain glutamine. Therefore, at present, postoperative total parenteral nutrition does not provide glutamine. Several modifications of the composition of the amino acid solutions given in total parenteral nutrition have been evaluated recently. Ornithine-alpha-ketoglutarate preserves muscle protein synthesis and spares nitrogen after elective surgery, and an extra supply of branched-chain amino acids improves muscle protein synthesis in animals. Patients undergoing elective abdominal surgery (n = 33) received isocaloric (135 kJ/kg body weight/24 h) and isonitrogenous (0.2 g N/kg body weight/24 h) total parenteral nutrition for three days immediately following surgery. Administration of glutamine and ornithine-alpha-ketoglutarate as part of the amino acid supply reduced the loss of muscle glutamine from 40% to 25% (P less than .05). Additional supplementation of branched-chain amino acids produced no such effect, however, as compared with the control group. Further clinical trials including glutamine and ornithine-alpha-ketoglutarate are advocated.

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.

History of parenteral nutrition

A survey is given of the development of parenteral nutrition with the beginning of William Harveys fantastic discovery of the circulation to todays discussion of what is an optimal regime of parenteral nutrition. The important and different steps of development during the 17th and 19th centuries are discussed. The modern steps during the last century leading to the concept we have today of parenteral nutrition is mentioned, with reference to all pioneers all over the world. Glucose, protein hydrolysates and crystalline amino acids, development of safe fat emulsions, and the current concepts of parenteral nutrition and future considerations are discussed.

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.

Growth hormone improves muscle protein metabolism and whole body nitrogen economy in man during a hyponitrogenous diet

Healthy male volunteers (n = 12) were given a normocaloric hyponitrogenous diet for a conditioning period of 7 days. Thereafter they were blindly randomized to receive daily injections of methionyl recombinant human growth hormone (met-hGH) 0.06 IU/kg or saline during a second week of hyponitrogenous nutrition. The met-hGH group showed a lower urinary urea excretion and a lower serum concentration of urea as compared with the control group. In skeletal muscle, the polyribosome concentration, indicative of muscle protein synthesis, as well as the concentrations of glutamine, alanine, aspartate, serine, and threonine, decreased in the control group, whereas no such changes were seen in the met-hGH-treated group. Since provision of met-hGH prevented protein catabolism in muscle and improved whole body nitrogen economy, investigations of the possible beneficial effects of met-hGH to prevent skeletal muscle vast after surgical trauma are advocated.

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.

Stress hormone and amino acid infusion in healthy volunteers : short-term effects on protein synthesis and amino acid metabolism in skeletal muscle

To study the immediate effects of stress hormones and intravenous amino acid support, healthy male volunteers were administered a stress-hormone infusion including epinephrine, cortisol, and glucagon either alone (Triple, n = 8) or combined with a balanced glutamine-free amino acid solution (Triple AA, n = 8) over a period of 6 hours. The amino acid infusion was started 2 hours after the hormone infusion. A third group (AA, n = 8) received the balanced amino acid solution alone. After 6 hours of the stress-hormone infusion, a decrease was observed in skeletal muscle protein synthesis as measured by the size distribution and concentration of ribosomes. The decrease was prevented by an infusion of the balanced amino acid solution. Following the triple-hormone infusion, a decrease was noted in the content of the total free amino acids in both muscle and plasma. After including amino acids in the infusion solution, the significant decrease in muscle glutamine caused by the triple hormones was not seen. Plasma cortisol, insulin, and glucose increased in response to the triple-hormone infusion alone or in combination with amino acids. In summary, the results show that the signs of muscle protein catabolism elicited by administration of stress hormones can be attenuated by simultaneous administration of a conventional amino acid solution, although it does not contain glutamine.

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.

Analogues to glutamine in clinical practice

Trauma is accompanied by a negative nitrogen balance and a loss of skeletal muscle proteins [1]. The changes in muscle protein metabolism are characterized by a decrease in protein synthesis [2] and a depletion of intracellular free glutamine [3]. These alterations are not prevented by postoperative TPN including conventional amino acid solutions.