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Biomedical subjects

E Vinnars

Publications and source records attributed to E Vinnars.

At least 37 records · Page 2Linked to original sources

Effects of insulin on myocardial uptake of branched chain amino acids soon after cardiac operations.

Infusion of insulin-glucose-potassium is used to support the failing heart after cardiac operations. Although the effects on myocardial uptake of carbohydrates and lipids have been described, the effects on myocardial extraction of amino acids are unknown. This study was undertaken to clarify the effect of insulin-glucose-potassium on the pattern of amino acid uptake/release in myocardial and skeletal muscle after coronary operations. The amino acid uptake/release of the heart and of the leg was studied in 18 patients 1 hour after coronary bypass operations. The patients were randomized to treatment with 25 U of fast-acting insulin as a bolus injection followed by a continuous infusion of 1 U/kg body weight for 1 hour, or to serve as control patients. The hyperinsulinemic "clamp" technique was used to keep blood glucose unchanged during the study. In the insulin-treated group, the arterial concentration of 17 of 22 individual amino acids, including the three branched chain amino acids, decreased, the remainder being unchanged. The amino acid uptake/release of the leg was unchanged. The net myocardial uptake of leucine and isoleucine shifted to a no-uptake/no-release in the insulin-treated group, whereas the no-uptake/no-release of tyrosine and phenylalanine turned into a significant release. A positive correlation was observed between arterial concentration and myocardial uptake/release of the three branched chain amino acids. It is suggested that insulin, by lowering the arterial concentration of leucine and isoleucine, inhibited the myocardial uptake of these amino acids. This may have a negative effect on postoperative myocardial protein balance suggested by the release of tyrosine and phenylalanine.

Amino Acids, Branched-Chain↗

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.

Amino Acids↗

Ribosome and free amino acid content in muscle during hemodialysis.

Patients (N = 8) with chronic renal failure and uremia treated with hospital hemodialysis were in a pilot study investigated before and after a single hemodialysis session. The extracorporeal dialysis circuit was flushed regularly with saline to avoid clotting and the use of heparin. Percutaneous skeletal muscle biopsies were taken before and after the dialysis to determine the content of free amino acids together with the concentration and size distribution of ribosomes before and after dialysis. After dialysis the alanine concentration in muscle decreased by 20% (P less than 0.05), while all other amino acids were unaffected. The total ribosome concentration per mg of DNA decreased by 31% (P less than 0.01) and the relative proportion of polyribosomes by 7% (P less than 0.05) after the dialysis compared to predialytic values. All individual plasma amino acids decreased during the dialysis procedure except for threonine and arginine, which were unaltered, and leucine and isoleucine, which increased. The decline in ribosome and polyribosome content together with the changes in amino acid levels indicate a low capacity for protein synthesis and increased catabolism in muscle of hemodialyzed patients.

Adolescent↗

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↗

Nitrogen requirements in severely injured patients.

The study was designed to evaluate nitrogen needs in severely injured patients during the first week after trauma. Thirty-nine patients aged from 18 to 65 years with a burn or fractures of more than two long bones were studied. Energy requirements were given parenterally as fat and glucose in isocaloric amounts. The patients were randomized into five groups receiving different amounts of nitrogen from zero to 0.3 g kg body-weight-1 24 h-1. Daily and cumulative nitrogen balance, urinary 3-methylhistidine excretion and nitrogen retention were calculated on days 2-8 after trauma. With no nitrogen, the mean(s.e.m.) daily nitrogen balance after the trauma was -13.8(0.5) gN. The balance improved markedly in groups with a nitrogen intake of up to 0.2 g kg body-weight-1 (P less than 0.001) compared with the no-nitrogen group. The 3-methylhistidine excretion increased because of the trauma in all groups with no statistically significant difference between the groups. Nitrogen retention decreased with increase in nitrogen supply and with time after injury. It is suggested that a nitrogen supply of 0.20 kg bodyweight-1 24 h-1 is optimal for severely injured patients during the first week after trauma.

Adolescent↗

Elective abdominal surgery depresses muscle protein synthesis and increases subjective fatigue: effects lasting more than 30 days.

Ten patients without metabolic disease undergoing elective cholecystectomy were studied before surgery and on days 3, 10, 20 and 30 after operation. Percutaneous muscle biopsies were taken and protein synthesis was determined from the total concentration and size distribution of ribosomes. The subjective feeling of fatigue was estimated using a visual analogue scale. The nitrogen balance was calculated at 20 days following surgery. The mean (s.e.m.) total concentration of ribosomes per milligram of DNA decreased by 27.5(6.6) per cent (P less than 0.01), 44.5(6.5) per cent (P less than 0.001), 48.3(8.9) per cent (P less than 0.001) and 45.0(8.2) per cent (P less than 0.01) on days 3, 10, 20 and 30, respectively. By 30 days after surgery no sign of restoration of normality was seen. The relative proportion of polyribosomes had decreased by 20.4(6.4) per cent (P less than 0.05) on the third postoperative day and by 20.4(3.9) per cent (P less than 0.01) on the tenth postoperative day and was restored to the preoperative level by day 20. The subjective fatigue score increased after operation and five of nine patients had not regained their preoperative scores 30 days after surgery. The daily nitrogen balance was negative for 5 days. The cumulated nitrogen losses were not restored until after 18 days following surgery. Elective abdominal surgery caused a sustained depression of protein synthesis for over 30 days, a longer period than previously presumed. These results show that long-term follow-up is required when the effect of different postoperative nutritional regimens are to be evaluated.

Cholecystectomy↗

Effect of a test meal, without and with protein, on muscle and plasma free amino acids.

1. The effect of a protein-free meal and a protein-rich meal on the concentration of free amino acids in plasma and muscle tissue was studied in eight healthy subjects. The energy content of the protein-free meal was 3800 kJ. The protein-rich meal was identical in composition except that 50 g of bovine serum albumin was added. Plasma and samples from the quadriceps femoris muscle (percutaneous muscle biopsy) for amino acid determination were collection before and at 1, 3, 5 and 7 h after the meal. 2. After the protein-free meal the concentrations of most essential amino acids and of some non-essential amino acids in plasma decreased continuously below basal levels at 5-7 h. The muscle concentration of essential amino acids fell too, reaching its nadir 3-5 h after the meal. The decrease in plasma amino acid concentration was smaller than the decrease in muscle concentration for all essential amino acids except phenylalanine. 3. The concentrations of most amino acids in plasma increased transiently 1 and 3 h after the protein-rich meal; histidine and several non-essential amino acids fell below the basal levels at 5-7 h after the meal. In muscle, threonine, valine, leucine, lysine and alanine were increased at 1 and 3 h after the protein-rich meal; isoleucine, serine and glycine fell below the basal level after 5 and 7 h. For the essential amino acids except threonine and lysine, the increase in plasma concentration was greater than the increase in muscle concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Trauma metabolism and the heart: studies of heart and leg amino acid flux after cardiac surgery.

Flux of plasma amino acids was measured across the heart and the leg (reflecting mainly skeletal muscle) in 18 patients 1 hour after completion of aorto-coronary bypass surgery. There was a net loss of amino acids from the leg (-324.9 +/- 39 nmol/min/100 ml tissue) while amino acid flux across the heart was not statistically different from zero. There were however positive intertissue correlations between leg and myocardial flux of tyrosine and most other amino acids, suggesting that protein metabolism of both tissues were affected in the same catabolic direction by the trauma response. Alanine and glutamine accounted for 50% of the amino acid release from the leg, which is in accordance with observations in association with other types of trauma. Alanine and glutamine also dominated amino acid release from the heart. Glutamate and aspartate were taken up by both tissues. The principal difference between the tissues was a myocardial uptake of leucine and isoleucine, in contrast to a leg release.

Adult↗

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↗

Water and electrolytes in muscle tissue and free amino acids in muscle and plasma in connection with transurethral resection of the prostate. I. Distilled water as an irrigating fluid.

10 patients undergoing transurethral resection of the prostate using sterile distilled water as an irrigating fluid were studied. The extra- and intracellular distribution of water, the total content of water and electrolytes and the free amino acid concentrations in muscle tissue were determined together with the concentrations of free amino acids in plasma preoperatively, immediately postoperatively and 2 hours postoperatively. The content of water and concentrations of electrolytes in skeletal muscle did not change significantly from the preoperative to the postoperative period with the exception of the potassium concentration, which decreased 2 hours postoperatively. The following free amino acid concentrations in muscle tissue showed significantly decreased values 2 hours postoperatively compared with the preoperative values: taurine, serine, glutamate, proline and leucine. The concentrations of non-essential amino acids in muscle decreased significantly 2 hours postoperatively. This may be interpreted as a dilution effect. An increased concentration of some amino acids in plasma postoperatively may be explained as a haemoconcentration effect due to the use of a postoperative diuretic.

Aged↗

Water and electrolytes in muscle tissue and free amino acids in muscle and plasma in connection with transurethral resection of the prostate. II. Isotonic 2.2% glycine solution as an irrigating fluid.

Seventeen patients undergoing transurethral resection of the prostate using isotonic 2.2% glycine solution as an irrigating fluid were studied. The extra- and intracellular distribution of water, the total content of water, and the concentrations of electrolytes and free amino acids in muscle tissue were determined together with the concentrations of free amino acids in plasma preoperatively, immediately postoperatively and 2, 6, 24 and 48 hours postoperatively in two groups with separate sampling periods. There were no significant changes in water content and sodium or chloride concentrations in muscle tissue postoperatively. Potassium and magnesium concentrations decreased late in the postoperative phase. In plasma there was a fifty-fold increase immediately postoperatively in the glycine concentration (mean fluid absorption 0.71) followed by a six-fold increase in muscle tissue 6 hours postoperatively. The glycine metabolite serine also increased in plasma and muscle. Other muscle amino acid concentrations decreased immediately postoperatively probably due to the massive glycine entrance into the cells. Later postoperative changes in some muscle amino acids (glutamine, glutamate, alanine, tyrosine and arginine) may be explained more by the operative trauma than by the influence of glycine. Two different types of metabolic effects are seen in this material. The first is that of the glycine infusion and the metabolic effects of glycine. The second is the catabolic influence of the surgical trauma. Accumulation of glycine in tissues in some patients with the possible production of ammonia and the effects of glycine as an inhibitory neurotransmitter must be considered as risk factors when choosing glycine as an irrigating fluid.

Aged↗

Glutamine and ornithine-alpha-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.

Abdomen↗

Availability of amino acids supplied by constant intravenous infusion of synthetic dipeptides in healthy man.

1. A commercial amino acid solution supplemented with two synthetic dipeptides, L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-tyrosine (Gly-Tyr), or alternatively with isonitrogenous amounts of free alanine and glycine has been continuously infused over 4 h in six apparently healthy volunteers. 2. The infusion of the solutions was not accompanied by any side effects and the volunteers reported no complaints. 3. Infusion of the alanine- and glycine-supplemented control solution resulted in an increase of the concentration of these amino acids, while no appreciable change in free glutamine concentration was observed and free tyrosine revealed a steady decrease throughout the infusion. 4. Infusion of the peptide-supplemented solution resulted in a prompt equimolar liberation of the constituent free amino acids (glutamine, alanine, tyrosine and glycine), approaching steady state after about 30 min infusion, while only trace but stable concentrations of the two dipeptides were measured throughout the infusion. No peptides were detectable in urine. The findings suggest a nearly quantitative extracellular hydrolysis of the infused dipeptides and indicate a subsequent utilization of the liberated free amino acids. 5. The estimated metabolic clearance rates and total body plasma clearances were very similar for the two dipeptides (Ala-Gln 35.9 +/- 9.5 ml min-1 kg-1 and 2.9 +/- 0.9 l/min, respectively; Gly-Tyr 33.7 +/- 9.5 ml min-1 kg-1 and 2.7 +/- 0.9 l/min, respectively); thus there is little difference in the metabolic handling of these dipeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurement of the rate of protein synthesis in muscle of postabsorptive young men by injection of a 'flooding dose' of [1-13C]leucine.

1. The 'flooding dose' technique for measuring the rate of protein synthesis in tissues in vivo involves the injection of a large amount of unlabelled amino acid together with the tracer to minimize differences in isotopic enrichment of the free amino acid in plasma and tissue compartments. This approach has been investigated in human muscle by taking biopsies from postabsorptive male volunteers given [1-13C]leucine. 2. Intravenous injection of 4 g of unlabelled leucine resulted in a rapid rise in free leucine concentration of seven- to eleven-fold in plasma and five-fold in muscle. Values were still elevated by two-fold after 2 h. 3. Five minutes after injection of [1-13C]leucine (0.05 g/kg) the isotopic enrichment of plasma leucine was 82% that of the injected material, falling to 44% at 120 min. The enrichment of free leucine in sequential muscle biopsies was close to that in plasma and almost identical to that for plasma alpha-ketoisocaproate. 4. The rate of protein synthesis was determined from the increase in leucine enrichment in protein of muscle biopsies taken before and 90 min after injection of [1-13C]leucine (0.05 g/kg; 19 or 39 atom% excess) and the average plasma alpha-ketoisocaproate enrichment over this period (taken to represent muscle free leucine). The mean rate of muscle protein synthesis in 10 subjects was 1.95 (SEM 0.12) %/day. Rates of protein synthesis calculated from plasma leucine as precursor enrichment were only 5% lower than those calculated from plasma alpha-ketoisocaproate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗