Biomedical subjects

L Wykes

Publications and source records attributed to L Wykes.

10 recordsLinked to original sources

PubMed2005

Randomized clinical trial of the anabolic effect of hypocaloric parenteral nutrition after abdominal surgery.

BACKGROUND: The observed failure of hypocaloric nutrition to establish an anabolic state after surgery may reflect inadequate control for the type and quality of analgesia in the studies performed. This study was designed to test the hypothesis that hypocaloric nutrition induces anabolism in patients who receive effective segmental pain relief using perioperative epidural analgesia. METHODS: Sixteen patients who underwent colorectal surgery and received epidural analgesia were randomly assigned to receive intravenous glucose either without (glucose only) or with amino acids (nutrition). Feeding was administered over 48 h from surgical skin incision until the second day after operation. Glucose provided 50 per cent of the patient's resting energy expenditure (REE). Amino acids were infused at rates that provided 20 per cent of REE. Leucine rate of appearance (Ra), leucine oxidation and non-oxidative leucine disposal (NOLD) were assessed by measuring L-[1-13C]leucine kinetics. A positive leucine balance, that is the difference between NOLD and leucine Ra, indicated anabolism. RESULTS: After surgery, leucine Ra in the nutrition group was lower than that in the glucose only group (mean(s.d.) 88(25) versus 131(22) micromol per kg per h). The leucine balance remained negative in the glucose only group, whereas it became positive in the nutrition group (mean(s.d.) -24(3) versus 38(12) micromol per kg per h; P < 0.001). CONCLUSION: Patients who receive hypocaloric parenteral nutrition can be rendered anabolic after colorectal surgery in the presence of epidural analgesia.

Amino Acids↗

PubMed2004

Effect of desflurane/remifentanil anaesthesia on glucose metabolism during surgery: a comparison with desflurane/epidural anaesthesia.

BACKGROUND: The aim of this study was to investigate the effect of general anaesthesia combined with remifentanil or epidural blockade on glucose metabolism during surgery. METHODS: We randomly assigned patients undergoing elective colorectal surgery to receive either desflurane anaesthesia supplemented with intravenous remifentanil (n = 7) or desflurane anaesthesia supplemented with epidural bupivacaine (n = 7). Plasma concentrations of glucose, lactate, free fatty acids (FFA), insulin, glucagon and cortisol were measured before and after 2 h of surgery. Pre- and intraoperative whole body glucose production and glucose clearance, an indicator of glucose uptake, were determined by an isotope dilution technique using [6,6-2H2]glucose. RESULTS: In both groups intraoperative glucose production ( P< 0.05) and uptake ( P< 0.05) decreased. Plasma glucose concentrations ( P< 0.05) increased during surgery but did not exceed the normal range (remifentanil group: 5.7 +/- 0.7 mmol l-1, epidural group: 5.8 +/- 0.4 mmol l-1). The plasma concentrations of lactate, FFA, insulin and glucagon remained unchanged during the operation. The plasma cortisol concentration in both groups increased intraoperatively (P< 0.05). CONCLUSION: Both desflurane/remifentanil and desflurane/epidural anaesthesia decrease the intraoperative rate of whole body glucose production, thereby attenuating the hyperglycaemic response to colorectal surgery.

Adult↗

PubMed2001

Integrated analysis of protein and glucose metabolism during surgery: effects of anesthesia.

The aim of this study was to assess dynamic changes in protein and glucose metabolism during surgery. Twelve patients undergoing colorectal surgery received either intravenous propofol anesthesia (n = 6) or inhalational anesthesia with desflurane (n = 6). Pre- and intraoperative protein and glucose kinetics were analyzed by an isotope dilution technique using L-[1-(13)C]leucine and [6,6-(2)H(2)]glucose. Plasma concentrations of glucose, lactate, free fatty acids, insulin, glucagon, and cortisol were measured before and after 2 h of surgery. The rates of appearance of leucine and glucose, leucine oxidation, protein synthesis, and glucose clearance decreased during surgery, independent of the type of anesthesia (P < 0.05). A correlation between the rate of appearance of leucine and glucose was observed (r = 0.755, P < 0.001). Intraoperative plasma cortisol and glucose concentrations increased (P < 0.05), whereas plasma concentrations of lactate, free fatty acids, insulin, and glucagon did not change. Surgery causes a depression of whole body protein and glucose metabolism, independent of the anesthetic technique. There is a correlation between perioperative glucose production and protein breakdown.

Adult↗

PubMed2000

Effect of epidural blockade on protein, glucose, and lipid metabolism in the fasted state and during dextrose infusion in volunteers.

BACKGROUND: To interpret correctly the results from studies performed during surgery and anesthesia it is necessary to dissect the separate effect of the anesthetic technique itself. The purpose of this study was to investigate the metabolic effects of epidural blockade (T7-S1) with bupivacaine 0.25% after 12 h fasting and during administration of 4 mg x kg(-1) x min(-1) dextrose in six healthy volunteers. METHODS: Each volunteer was assigned to randomly undergo a 6-h multiple stable isotope infusion study (3 h fasted, 3 h dextrose infusion) with or without epidural blockade. L-[1-13C]leucine, [6,6-2H2]glucose, and [1,1,2,3,3-2H5]glycerol were infused to measure protein synthesis, breakdown, and amino acid oxidation; glucose production and clearance; and lipolysis. Plasma concentrations of glucose, lactate, glycerol, free fatty acids, insulin, and glucagon were determined. RESULTS: Epidural blockade with bupivacaine had no influence on protein oxidation, breakdown and synthesis, glucose production, glucose clearance and lipolysis in the fasted state. Plasma concentrations of metabolic substrates and hormones also were not affected. Dextrose infusion significantly increased glucose clearance and plasma concentrations of glucose and insulin, while endogenous glucose production and lipolysis decreased to a similar degree in both groups. Protein synthesis, breakdown, and oxidation did not change during dextrose infusion. CONCLUSIONS: Epidural blockade with bupivacaine in the absence of surgery has no effect on fasting protein, glucose, and lipid metabolism. Epidural blockade does not modify the inhibitory influence of dextrose administration on endogenous glucose production and lipolysis.

Adult↗

PubMed2000

Epidural blockade improves substrate utilization after surgery.

The purpose of this study was to test the hypothesis that epidural blockade with local anesthetic improves the anticatabolic effects of glucose after colorectal surgery. Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h glucose infusion at 4 mg. kg(-1). min(-1)) on the second postoperative day with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, and glucose production and clearance were assessed by L-[1-(13)C]leucine and [6, 6-(2)H(2)]glucose. Epidural blockade did not affect protein and glucose metabolism in the fasted state. Glucose infusion increased glucose clearance (P < 0.05), accompanied by an increase in the respiratory quotient (P < 0.05) and a decrease in leucine oxidation (P < 0.05) only in the presence of epidural blockade. An inverse correlation (r = -0.74, P < 0.05) between changes in glucose clearance and leucine oxidation was observed. In conclusion, epidural blockade facilitates whole body glucose uptake and inhibits endogenous protein oxidation after abdominal surgery, indicating a shift from a protein to a more glucose-dominated substrate utilization.

Aged↗

PubMed1999

Chronic protein undernutrition and an acute inflammatory stimulus elicit different protein kinetic responses in plasma but not in muscle of piglets.

The changes in protein metabolism of severe childhood malnutrition are generally perceived as a metabolic adaptation to chronic protein undernutrition. However, severe malnutrition is invariably accompanied by infections which also have profound effects on protein metabolism. This study aimed to distinguish the effect of protein undernutrition from that of an inflammatory stimulus on muscle and plasma protein synthesis rates. Two groups of five piglets consumed diets containing either 23% or 3% protein for 4 wk. They then were infused intravenously with 2H3-leucine before and 48 h after subcutaneous injections of turpentine to measure the fractional synthesis rates (FSR) of muscle protein and both the FSR and the absolute synthesis rates (ASR) of albumin and fibrinogen. Prior to turpentine injection, compared to control piglets, protein-deficient piglets had significantly lower muscle FSR and plasma concentrations of both albumin and fibrinogen, although only albumin had lower FSR and ASR. Turpentine injection decreased muscle FSR but increased the FSR, ASR and plasma concentrations of both albumin and fibrinogen in control piglets. In protein-deficient piglets, the inflammatory stress caused a further decrease in muscle protein FSR and in plasma albumin concentration despite marked increases in albumin FSR and ASR. Fibrinogen FSR, ASR and plasma concentration were increased. We conclude that protein undernutrition and inflammation elicit the same kinetic response in muscle protein but different kinetic responses in plasma proteins. Furthermore, whereas protein deficiency reduces the plasma albumin pool via a reduction in albumin synthesis, inflammation reduces it through a stimulation of catabolism and/or loss from the intravascular space.

Animals↗

PubMed1997

Lactase phlorizin hydrolase synthesis is decreased in protein-malnourished pigs.

We have examined the effect of protein malnutrition on brush border (BB) lactase phlorizin hydrolase (LPH) synthesis in young pigs. Two groups of four 3-wk-old pigs were fed diets containing either 19 g soy protein, 63 g carbohydrate and 5 g fat per 100 g diet (a protein-sufficient diet) or 3 g soy protein, 85 g carbohydrate and 5 g fat per 100 g diet (a protein-deficient diet). After 8 wk of consuming the diets, pigs were infused intravenously with 2H3-leucine for 8 h, then killed. The jejunum was collected for measurement of lactase activity, LPH mRNA abundance and the rate of LPH post-translational synthesis. Lactase activities did not differ between groups (mean 8.1 +/- 1.2 micromol x min(-1) x g mucosa(-1)). LPH mRNA abundance relative to elongation factor-1alpha mRNA (the constitutive/reference mRNA) was significantly (P < 0.05) higher in well-nourished pigs (0.36 +/- 0.03%) than in protein-malnourished pigs (0.21 +/- 0.02%). The rate constants of BB LPH post-translational synthesis were also significantly higher in the well-nourished (103 +/- 9% x d(-1)) than in the protein-malnourished pigs (66 +/- 8% x d(-1)). Further, the absolute synthesis rate of BB LPH, a measure of the amount of enzyme synthesized per gram of tissue, was significantly higher in well-nourished than in protein-malnourished pigs (in arbitrary units, 892 +/- 90 vs. 450 +/- 34, respectively). Thus, protein malnutrition affects both LPH mRNA abundance and post-translational processing in young pigs.

Animals↗

PubMed1997

Enteral glutamate is the preferential source for mucosal glutathione synthesis in fed piglets.

To measure the source and rate of mucosal glutathione (GSH) synthesis, fed piglets (28 days old; 7.7 kg) received a 6-h infusion of intragastric [U-13C]glutamate (n = 11) either with (n = 5) or without (n = 6) an intragastric infusion of [1-13C]glycine (0-6 h) and [1,2-13C2(U-13C)]glycine (3-6 h). Eighty-four percent of the labeled mucosal GSH-glutamate and 86% of the luminal GSH-glutamate was 13C5. The tracer-to-tracee ratio of GSH-[U-13C]glutamate was 75% of that of mucosal glutamate. Sixty percent of the labeled mucosal glutamate was 13C1, 13C2, or 13C3, but the tracer-to-tracee ratios of these isotopomers in GSH-glutamate were not significantly different from zero. After 3 h of infusion, the tracer-to-tracee ratio of GSH-[U-13C]glycine was 46%, and after 6 h of infusion GSH-[13C1]glycine was 82% of that of mucosal glycine. This suggested that the half-life of mucosal GSH was 2.7 +/- 0.1 h. We concluded that, in fed piglets, mucosal GSH-glutamate derived largely from the direct metabolism of enteral glutamate rather than from glutamate that was metabolized within the mucosa.

Animals↗

PubMed1996

Chronic protein deficiency differentially affects the kinetics of plasma proteins in young pigs.

The use of plasma protein concentrations to assess protein-nutritional status has been questioned because concentrations and kinetics are affected by factors other than protein intake. To determine the effect of protein deficiency on plasma protein concentration and synthesis, two groups of four piglets consumed diets containing either 20 or 3% protein. After 8 wk, 2H3-leucine was infused intravenously to measure the fractional and absolute synthesis rates (FSR and ASR) of albumin, transferrin, retinol binding protein (RBP), transthyretin (TTR), a new peptide called TTR2, the high density apolipoprotein (HDL-apoA-1), fibrinogen, and haptoglobin. Compared with controls, protein-deficient pigs had significantly lower (P < 0.05) plasma albumin, RBP and TTR2 concentrations, significantly slower (P < 0.05) FSR of fibrinogen, HDL-apoA-1, transferring and TTR2, significantly lower (P < 0.05) ASR of albumin, fibrinogen, transferrin, and TTR2, and a significantly higher (P < 0.05) ASR of TTR. Fibrinogen and transferrin concentrations did not differ between groups, but transthyretin concentration was higher in protein-deficient pigs. These results suggest that protein-nutritional status cannot be predicted from the concentrations of all plasma proteins, that chronic protein deficiency affects the rate of synthesis of only some plasma proteins, and that the kinetic response of plasma proteins to protein restriction cannot be predicted from measurements of plasma concentrations.

Aging↗

PubMed1996

Enteral glutamate is almost completely metabolized in first pass by the gastrointestinal tract of infant pigs.

We studied the absorption of enteral glutamate and phenylalanine using isotopic tracer and arteriovenous difference techniques. Six piglets, implanted with portal, carotid, and gastric catheters and an ultrasonic portal flow probe received a 6-h intragastric infusion of [U-13C] glutamate and [2H] phenylalanine, with a high-protein diet offered one time each hour. Amino acid concentrations and the isotopic enrichments of all mass isotopomers of glutamate, glutamine, and phenylalanine were measured in portal and arterial blood over the last hour. There was significant (P<0.025) net absorption of the indispensable amino acids as well as arginine, proline, serine, and alanine. There was no portal uptake of glutamate, aspartate, and glycine, and arterial glutamine was removed by the portal drained viscera (P<0.05). At isotopic steady state, 72% of the [2H] phenylalanine but only 5% of the [U-13C] glutamate tracer appeared in the portal blood. We conclude that, in fed infant pigs, the gut metabolizes virtually all of the enteral glutamate during absorption. Therefore, glutamate and glutamine in the body as a whole must derive almost entirely from synthesis de novo.

Amino Acids↗