Documentation of clinical benefit of specific aminoacid nutrients.
Explore the source record for details and available documents.
Arginine↗
Biomedical subjects
J Wernerman
Publications and source records attributed to J Wernerman.
[Effect of transcutaneous electric muscle stimulation on postoperative muscle mass and protein synthesis].
In an experimental study, 13 patients undergoing major elective abdominal surgery were given postoperative transcutaneous electrical muscle stimulation (TEMS) to the quadriceps femoris muscle on one leg, where the opposite leg served as a control. Changes in cross sectional area (CSA) and muscle protein synthesis were assessed by CT-scan and percutaneous muscle biopsies for ribosome analysis before surgery and on the sixth postoperative day. The percentage of polyribosomes in the ribosome suspension decreased significantly (p < 0.03) after operation in control legs, but not in stimulated legs (p > 0.16). The total concentration of ribosomes decreased significantly in TEMS legs (p < 0.03), but not in control legs (p > 0.16) CSA decreased significantly in both legs. The decrease in polyribosomes and CSA after operation was significantly less in TEMS legs than in controls (p < 0.05). TEMS may be a simple and effective method to improve muscle protein synthesis and muscle mass after abdominal surgery and should be evaluated in other catabolic states with muscle wasting.
Adult↗
Enteral nutrition in intensive care patients: a practical approach. Working Group on Nutrition and Metabolism, ESICM. European Society of Intensive Care Medicine.
Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of the management of these patients. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decisions when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements, and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.
Cost-Benefit Analysis↗
Renal effects of alpha-ketoglutarate early after coronary operations.
BACKGROUND: Alpha-ketoglutarate (alpha-KG) is a Krebs cycle intermediate and the carbon skeleton of glutamate. Alpha-ketoglutarate has provoked interest in heart surgery because of its proposed critical role in myocardial metabolism. This study investigates the role of alpha-KG in renal function after cardiac surgical procedures. METHODS: Twenty-two patients with normal preoperative renal function were included in a prospective, randomized, and controlled study. Eleven patients received intravenous infusion of 30 g alpha-KG/hour after the operation. Measurements were performed before operation, immediately after operation, and after 30 minutes of alpha-KG infusion. RESULTS: Renal blood flow was higher during alpha-KG infusion, 297% +/- 97% (of preoperative value), than in controls, 125% +/- 20% (p < 0.05). Filtration fraction was lower (12.3% +/- 0.05% versus 17.2% +/- 1.1%, p < 0.01), which prevented a significant difference in glomerular filtration rate. The renal arteriovenous differences of lactate, glutamate, glutamine, and glycine changed toward a net release during alpha-KG infusion. CONCLUSIONS: Infusion of alpha-KG enhances renal blood flow early after coronary surgical procedures in patients with normal renal function. The mechanism is unclear, but could be associated with primarily metabolic effects, and may potentially convey a beneficial effect for renal function.
Adult↗
The effect of unloading on protein synthesis in human skeletal muscle.
Atrophy of skeletal muscle is observed in response to immobilization and lack of weight-bearing. The aim of this study was to investigate the effect of immobilization on muscle protein synthesis and associated biochemical parameters in skeletal muscle of healthy volunteers employing a standardized model of lower limb unloading. One leg was unloaded for 10 days, and percutaneous muscle biopsies were taken before and at the end of the unloading period. The capacity for protein synthesis, as reflected by the concentration of RNA, decreased by 16% (P < 0.05) although the fractional synthesis rate (FSR) of protein was not significantly changed after 10 days of unloading. Furthermore there was an increase in the concentration of the free branched chain amino acids in muscle by 48% (P < 0.05).
Adult↗
Tissue protein synthesis rates in critically ill patients.
OBJECTIVES: The aims of this study were to simultaneously determine the in vivo rates of protein synthesis in skeletal muscle, peripheral blood lymphocytes, and serum albumin in critically ill patients; to establish whether a relationship between the responses of these tissues could be observed; and to demonstrate if a protein synthesis pattern characteristic of critical illness exists. DESIGN: Descriptive study. SETTING: Intensive care unit of a 1000-bed university hospital. PATIENTS: Fifteen patients treated in the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rates of tissue protein synthesis were determined in vivo once during the course of critical illness, using the flooding method with L-(2H5)phenylalanine. Protein synthesis in muscle was 1.49 +/- 0.16%/day; in circulating lymphocytes (i.e., mononuclear cells), protein synthesis was 11.10 +/- 1.82%/day. Albumin synthesis was 12.81 +/- 1.23%/day when expressed as the fractional rate, and was 184 +/- 19 mg/kg/day when expressed as the absolute rate. CONCLUSIONS: The individual tissues responded differently to trauma, and showed a wide range of values. The responses were not significantly correlated with each other and no pattern of tissue protein synthesis characteristic of critical illness was observed. However, both muscle protein and albumin synthesis rates correlated with metabolic status and clinical indices of the severity of illness.
Adult↗
Surgical trauma decreases glutathione synthetic capacity in human skeletal muscle tissue.
To gain insight into cellular metabolism underlying the glutathione (GSH) alterations induced by surgical trauma, we assessed postoperative skeletal muscle GSH metabolism and its redox status in 10 patients undergoing elective abdominal surgery. Muscle biopsy specimens were taken from the quadriceps femoris muscle before and at 24 and 72 h after surgery. GSH concentrations decreased by 40% at 24 h postoperatively compared with the paired preoperative values (P < 0.001) and remained low at 72 h (P < 0.01). The concentration of GSH disulfide (GSSG) did not significantly change throughout the study period, whereas the total GSH (as GSH equivalent) concentration decreased after surgery. Of the GSH constituent amino acids, the concentration of cysteine remained unchanged throughout the study period (from 28.2 +/- 10.1 preoperatively to 29.4 +/- 13.9 at 24 h postoperatively and to 28.3 +/- 15.6 micromol/kg wet wt at 72 h postoperatively). Despite a reduction in glutamate concentration by 40% 24 h after surgery, no correlation was established between GSH and glutamate concentrations postoperatively. Activity of gamma-glutamylcysteine synthetase did not change significantly after surgery, whereas GSH synthetase activity decreased postoperatively (from 66.4 +/- 19.1 preoperatively to 41.0 +/- 10.5 24 h postoperatively, P < 0.01, and to 46.0 +/- 11.7 microU/mg protein 72 h postoperatively, P < 0.05). The decrease of GSH was correlated to the reduced GSH synthetase activity seen at 24 h postoperatively. These results indicate that the skeletal muscle GSH pool is diminished in patients after surgical trauma. The depletion of the GSH pool is associated with a decreased activity of GSH synthetase, indicating a decreased GSH synthetic capacity in skeletal muscle tissue.
Aged↗
The synthesis rates of total liver protein and plasma albumin determined simultaneously in vivo in humans.
Although the metabolism of liver-derived plasma proteins such as albumin has been extensively studied, human hepatic protein synthesis as a whole has not been well characterized, because a reproducible model for obtaining human liver tissue has not been available. In this study, the fractional synthesis rates of total liver protein and albumin in vivo were determined simultaneously in nine subjects undergoing elective laparoscopic cholecystectomy. L-[2H5]phenylalanine (45 mg/kg body wt) was administered for 10 minutes intravenously. Blood samples were collected at regular intervals for 90 minutes and a liver biopsy specimen was taken at 35 +/- 7 minutes. The enrichments of plasma free phenylalanine, plasma albumin, and total liver protein were measured with gas chromatography mass spectrometry (GC-MS). The fractional synthesis rate (FSR) of total liver protein was 24.7 +/- 3.1 %/d (mean +/- SD), and that of albumin was 5.9 +/-1.2%/d. The amount of albumin synthesized per day (absolute synthesis rate, ASR) was 109 +/- 21 mg/kg body wt. No correlation between FSR of total liver protein and ASR of albumin was found. It is concluded that the technique of obtaining liver tissue specimens during laparoscopic surgery may serve as a human in vivo model to study total liver protein synthesis. The fractional synthesis rate of total liver proteins (stationary and exported), equals approximately 25% of the liver protein content daily. Within the range of values of this study, the absolute synthesis rate of albumin was not correlated to the fractional synthesis rate of total liver protein.
Adult↗
Addition of alpha-ketoglutarate to blood cardioplegia improves cardioprotection.
BACKGROUND: We hypothesized that myocardial content of alpha-ketoglutarate (alpha-KG), an intermediate of the Krebs cycle, can be critically low during heart operations, and that provision of alpha-KG could reduce metabolic abnormalities and lead to improved myocardial protection. METHODS: Twenty-four men aged 46 to 78 years who were undergoing heart operations participated in a prospective, controlled, randomized study. In 13 patients, an average of 28 g of alpha-KG was added to blood cardioplegia. Plasma creatine kinase isoenzyme MB and troponin T, and myocardial extraction of oxygen, substrates, and amino acids were measured. RESULTS: alpha-Ketoglutarate treatment was associated with lower creatine kinase isoenzyme MB (F = 39.6, df = 1.172, p < 0.001) and lower troponin (F = 12.9, df = 1.172, p < 0.001). The values at 4 hours were 31 +/- 2.4 microg/L versus 49 +/- 4.9 microg/L (creatine kinase isoenzyme MB) and 1.1 +/- 0.05 microg/L versus 2.0 +/- 0.34 microg/L (troponin T). Myocardial oxygen extraction was higher during alpha-KG cardioplegia (p < 0.01), but there were no significant differences in myocardial uptake or release of substrates or amino acids. Lactate release was observed in both groups during cardioplegia. Myocardial lactate release had ceased after 30 minutes of reperfusion in nearly half the alpha-KG-treated patients (6 of 13) but remained in all the control patients (11 of 11, p = 0.016). There were no other differences after 30 minutes of reperfusion. CONCLUSION: Provision of alpha-KG during blood cardioplegia improves myocardial protection in patients undergoing coronary operations. This may be linked to enhanced oxidation.
Aged↗
Insulin and amino acid infusion after cardiac operations: effects on systemic and renal perfusion.
OBJECTIVE: The purpose of this study was to answer two questions: (1) Does a mixed amino acid infusion enhance systemic and renal perfusion in the early postoperative period after heart operations? (2) Does the addition of insulin (glucose-insulin-potassium solution) provide additional effects to those of an amino acid infusion? METHODS: Thirty-three male patients undergoing coronary artery bypass grafting (mean age 65.9 +/- 1.2 years) were included in a prospective, controlled, randomized study. Eleven patients (AA group) received infusion of mixed amino acids (11.4 gm), 11 patients (AA + GIK group) received infusion of mixed amino acids (11.4 gm) and insulin solution (225 IU insulin, glucose with glucose clamp technique, and potassium), and 11 patients served as control subjects. RESULTS: Amino acid infusion alone had no effect on systemic vascular resistance or cardiac index but increased renal blood flow 51% +/- 11% (from 114 +/- 13 to 172 +/- 24 ml.min-1.m-2 in one kidney, p < 0.05 vs the control group). Insulin solution in addition to amino acid infusion reduced systemic vascular resistance 24% +/- 3% (from 1280 +/- 85 to 960 +/- 57 dyn.sec.cm-5, p < 0.05 vs the control and AA groups) and increased cardiac index 13% +/- 3% (from 2.3 +/- 0.2 to 2.6 +/- 0.2 L.min-1.m-2, p < 0.05 vs the control and AA groups). Insulin had no significant additive effect on renal blood flow. CONCLUSIONS: Our data imply that (1) infusion of mixed amino acids enhances renal blood flow after cardiac operations but has no effect on systemic perfusion and (2) the addition of insulin solution improves systemic perfusion. The combined treatment may potentially reduce the risk of renal hypoperfusion injury in the postoperative period after coronary artery bypass grafting.
Adult↗
Longitudinal changes of biochemical parameters in muscle during critical illness.
The study was undertaken to characterize the time course of biochemical parameters in skeletal muscle during critical illness to gain information for the design of a suitable protocol for interventional studies using metabolic or nutritional manipulation. Critically ill patients in our intensive care unit ([ICU] N = 9) were investigated on two separate sampling occasions with percutaneous muscle biopsies for determination of protein, nucleic acids, free amino acids, energy-rich phosphates, fat, water, and electrolytes. The first biopsy specimen was taken 3 to 11 days after admission and the second biopsy specimen 3 to 7 days later. Protein concentration, expressed as alkali-soluble protein (ASP)/DNA, decreased by 12% (P < .02) between the two biopsies. The total free amino acid content was only 50% of normal, but remained unaltered over time. In particular, the concentration of glutamine remained low, approximately 25% of normal. In contrast, branched-chain amino acid (BCAA) increased by 25% (P < .05) and phenylalanine by 55% (P < .05) between biopsies. The fat content related to fat-free solid (FFS) increased by 130% (P < .001) between the two biopsies. Muscle water did not change during the study period. The extracellular portion was double the normal value when related to FFS. Intracellular water, on the other hand, was outside the 95% confidence interval for normal values in the second biopsy. The concentrations of adenosine triphosphate (ATP), creatine, phosphocreatine, and the phosphorylated fraction of total creatine remained at the same level between the two biopsies. We conclude that in critically ill patients, there is a decrease in protein content over time and increases in BCAA, phenylalanine, and fat content, while the low glutamine level and high extracellular water content remain unaltered. The temporal alterations were well characterized after a 5-day study period.
Adult↗
Nutrition in the ICU--from overfeeding to starvation.
Explore the source record for details and available documents.
Humans↗
Skeletal muscle glutathione is depleted in critically ill patients.
OBJECTIVE: To investigate the concentrations of reduced and total glutathione in relation to the muscle free amino acid pattern in critically ill patients and matched healthy controls. DESIGN: Prospective case control. SETTING: University hospital intensive care unit (ICU). PATIENTS: Eleven critically ill patients in the intensive care unit were studied after a stay of at least 4 days. Eleven age- and gender-matched metabolically healthy patients undergoing elective surgical procedures served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Reduced and total glutathione concentrations were determined in skeletal muscle, in plasma, and in whole blood, together with muscle free amino acid concentrations. In the ICU group, reduced and total glutathione values were 57% and 62%, respectively, of the values seen in the control group (p < .001). In addition, a decreased ratio between reduced and total glutathione compared with the controls was seen (0.80 as compared with 0.91, p < .001). The glutamine concentration in skeletal muscle in the ICU group was 72% lower compared with that value seen in healthy controls (p < .001). Correlations were found between the concentrations of glutamine and the total muscle glutathione (r2 = .46, p < .001), as well as between glutamine and the ratio of reduced and total glutathione (r2 = .45, p < .001) in skeletal muscle, suggesting that the redox status of glutathione and the glutamine status of the tissue are related. CONCLUSIONS: Critical illness is associated with alterations in muscle glutathione metabolism. The muscle-reduced glutathione concentrations decrease and, in addition, the ratio between reduced and total glutathione decreases, indicating a situation of oxidative stress in this tissue. This decrease may impair the defense of muscle against oxygen free radicals and influence amino acid transport, thus contributing to the loss of balance between protein synthesis and protein degradation that is characteristic of protein catabolism.
Adult↗
Enteral or parenteral nutrition? Pro-parenteral.
Explore the source record for details and available documents.
Critical Care↗
Measurement of human growth hormone receptor messenger ribonucleic acid by a quantitative polymerase chain reaction-based assay: demonstration of reduced expression after elective surgery.
Studies of GH receptor (GHR) gene expression in human tissues have been hampered by the limited amount of tissue available for analysis and the low sensitivity of conventional methods. We have developed a quantitative reverse transcriptase-PCR assay for measurement of GHR messenger ribonucleic acid levels in small human tissue biopsies. To compensate for sample to sample variation, an internal RNA standard, which differs from the wild-type GHR transcript by only a few nucleotides, was reverse transcribed and amplified together with the GHR transcripts. PCR was carried out using one biotinylated primer to permit the purification of single stranded PCR products on streptavidin-coated microtiter plates. The ratio between the wild-type and mutated transcripts was determined by two separate minisequence reactions in which a primer, annealed immediately 3' of a variable nucleotide, was extended by a single 3H-labeled nucleotide, complementary to either the wild-type or mutated sequence. The assay range was 0.125-8 x 10(5) transcripts/sample, the mean intraassay coefficient of variation was 8.7%, and the lower limit of detection was 0.125 x 10(5) transcripts/sample. GHR messenger ribonucleic acid levels were detectable in small amounts (10-100 ng) of total RNA extracted from adipose tissue, skeletal muscle, and liver. The GHR gene expression in liver was approximately 10-fold higher than that in skeletal muscle, whereas intermediate levels were found in adipose tissue. In nine patients undergoing elective abdominal surgery, GHR gene expression in skeletal muscle was reduced on day 3 after surgery compared to the baseline level. The decrease in GHR gene expression was accompanied by a decrease in skeletal muscle glutamine. This suggests that the postoperative protein catabolism may be caused at least partly by acquired GH insensitivity due to reduced expression of the GHR gene.
Abdomen↗
Correction of acidosis in dialysis patients increases branched-chain and total essential amino acid levels in muscle.
Earlier studies have shown increased oxidation of the branched-chain amino acids (BCAA), valine, isoleucine and leucine, in experimental acidosis and low levels of valine in the muscle of acidotic HD patients. Using HPLC, free amino acids in plasma and muscle were studied before and after correction of acidosis in 9 HD patients over 6 months by dialysis with a high bicarbonate solution. The predialysis standard bicarbonate concentration in blood increased from 20.6 +/- 1.3 mmol/l (mean +/- SD) before correction of acidosis to 25.9 +/- 1.8 mmol/l after correction. Correction of acidosis resulted in a significant increase in the i.c. concentrations of valine, isoleucine and leucine by 48%, 28% and 32%, as well as for the sum of BCAA and EAA, from a level lower than controls. The intra- and extracellular gradient increased for several amino acids and for the sum of EAA and BCAA, suggesting an increased influx or reduced efflux of amino acids across the cell membrane. Anthropometric data and the levels of S-albumin and transferrin did not change after correction of acidosis. The increases in the i.c. concentrations of BCAA after correction of acidosis suggest that the catabolism of these amino acids had been reduced. The effects of correction of acidosis on the concentrations of essential amino acids could be beneficial since low concentrations in muscle may reduce protein synthesis.
Acidosis↗
Effect of transcutaneous electrical muscle stimulation on postoperative muscle mass and protein synthesis.
In an experimental study, 13 patients undergoing major elective abdominal surgery were given postoperative transcutaneous electrical muscle stimulation (TEMS) to the quadriceps femoris muscle on one leg; the opposite leg served as control. Changes in cross-sectional area (CSA) and muscle protein synthesis were assessed by computed tomography and ribosome analysis of percutaneous muscle biopsies before surgery and on the sixth postoperative day. The percentage of polyribosomes in the ribosome suspension decreased significantly (P < 0.03) after operation in control legs, but not in stimulated legs (P > 0.16). The total concentration of ribosomes decreased significantly in legs treated with TEMS (P < 0.03) but not in control legs (P > 0.16). CSA decreased significantly in both legs. The decrease in polyribosomes and CSA after operation was significantly less in stimulated legs than in controls (P < 0.05). TEMS may be a simple and effective method for improving muscle protein synthesis and muscle mass after abdominal surgery and should be evaluated in other catabolic states with muscle wasting.
Abdomen↗
Protein synthesis rates of skeletal muscle, lymphocytes, and albumin with stress hormone infusion in healthy man.
The rate of protein synthesis was assessed in muscle, lymphocytes, and albumin in healthy volunteers administered an infusion of 6.0 micrograms cortisol +3.0 ng glucagon +0.5 nmol epinephrine min-1.kg-1. Protein synthesis in muscle tissue was not sensitive to the immediate effects of hormone infusion, but decreased significantly by 18 hours after the infusion had ceased (1.77% +/- 0.12% per day v 1.29% +/- 0.10%, P < .05). The rate of protein synthesis in lymphocytes was acutely sensitive to the effect of the hormone infusion, decreasing from 7.15% +/- 1.02% per day to 2.47% +/- 0.5% (P < .05). However, measurements made 18 hours after the end of the hormone infusion indicated that lymphocyte protein synthesis returned to the preinfusion rates. The rate of albumin synthesis was unaltered during infusion of the stress hormones, but was significantly increased when measured 18 hours after ending the hormone infusion (6.84% +/- 0.43% per day v 7.99% +/- 0.45%, P < .05). Thus, tissues respond differently to stress hormone infusion, demonstrating the importance of studying multiple organ systems when assessing the regulation of protein metabolism.
Adult↗