Epidural Ropivacaine versus  Epidural Morphine and the Catabolic Response to Colonic Surgery

2004 ◽  
Vol 100 (4) ◽  
pp. 973-978 ◽  
Author(s):  
Thomas Schricker ◽  
Linda Wykes ◽  
Leopold Eberhart ◽  
Ralph Lattermann ◽  
Franco Carli
Keyword(s):  
Protein Synthesis ◽  
Epidural Analgesia ◽  
Protein Oxidation ◽  
Glucose Production ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Oxidation Rates ◽  
Metabolic Substrates ◽  
Catabolic Response

Background The authors examined the hypothesis that epidural administration of local anesthetic, in contrast to epidural analgesia with morphine, inhibits postoperative protein oxidation during administration of glucose. Methods Fourteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding with 4 mg.kg(-1).min(-1) glucose) on the second day after colorectal surgery using epidural analgesia with either continuous ropivacaine or intermittent morphine. Protein synthesis, breakdown and oxidation, and glucose production were measured by L-[L-13C]leucine and [6,6-2H2]glucose. Substrate oxidation rates were determined by indirect calorimetry. Plasma concentrations of metabolic substrates and hormones were also measured. Results Whole body protein breakdown, oxidation, synthesis, and glucose production in the fasted state were similar between the two groups. Glucose administration decreased protein breakdown (P = 0.01), protein synthesis (P = 0.001), and glucose production (P = 0.001) to the same extent in both groups, whereas protein oxidation was not significantly affected. The type of epidural analgesia did not significantly influence the circulating concentrations of metabolic substrates and hormones in the fasted or in the fed state. Carbohydrate oxidation rate in the ropivacaine group was greater than in patients receiving morphine (P = 0.04), regardless of whether glucose was infused. Conclusion Epidural analgesia achieved with ropivacaine or morphine does not suppress the catabolic response to surgery, either under fasting conditions or in the presence of an energy supply.

Postoperative Infusion of Amino Acids Induces a Positive Protein Balance Independently of the Type of Analgesia Used

2006 ◽  
Vol 105 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Francesco Donatelli ◽  
Thomas Schricker ◽  
Giovanni Mistraletti ◽  
Francisco Asenjo ◽  
Piervirgilio Parrella ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Epidural Analgesia ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Protein Balance ◽  
Body Protein ◽  
Leucine Oxidation ◽  
Endogenous Glucose

Background Net loss of body protein is a prominent feature of the catabolic response to surgical tissue trauma. Epidural analgesia with hypocaloric dextrose has been demonstrated to attenuate leucine oxidation but was unable to make protein balance positive. The current study was set to determine whether an infusion of amino acids on the second day after colon surgery would revert the catabolic state and promote protein synthesis while maintaining glucose homeostasis in patients receiving epidural analgesia as compared with patient-controlled analgesia with morphine (PCA). Methods Sixteen patients undergoing colorectal surgery were randomly assigned to receive epidural blockade or PCA as analgesic techniques and underwent a 6-h stable isotope infusion study (3 h fasted, 3 h fed) on the second postoperative day. Whole body glucose kinetics and protein turnover were measured using [6,6-2H2]glucose and l-[1-13C]leucine as tracer. Results The infusion of amino acids caused a decrease in endogenous glucose rate of appearance in both groups (P < 0.05), with greater changes in the PCA group (P < 0.05). Administration of amino acids suppressed the appearance of leucine from protein breakdown in both groups (P < 0.05), although the decrease was greater in the PCA group (P < 0.05). Leucine oxidation increased in both groups (P < 0.05), with greater change in the epidural group (P < 0.05). Protein synthesis increased to the same extent in both groups (P < 0.05). Protein balance became positive after the infusion of amino acids, and the effect was greater in the PCA group (P < 0.05). Conclusions Infusion of amino acids decreased the endogenous glucose production and induced a positive protein balance independent of the type of anesthesia provided, although such effects were greater in the PCA group.

Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth

1991 ◽  
Vol 261 (1) ◽  
pp. R106-R116
Author(s):  
N. W. Istfan ◽  
P. R. Ling ◽  
G. L. Blackburn ◽  
B. R. Bistrian
Keyword(s):  
Protein Synthesis ◽  
Protein Metabolism ◽  
Whole Body ◽  
Independent Effect ◽  
Yoshida Sarcoma ◽  
Protein Breakdown ◽  
Body Protein ◽  
Breakdown Rates ◽  
Made In

To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of “whole body” protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification.

Whole-Body Protein Turnover before and after Resection of Colorectal Tumours

1983 ◽  
Vol 64 (1) ◽  
pp. 101-108 ◽  
Author(s):  
R. E. Glass ◽  
E. B. Fern ◽  
P. J. Garlick
Keyword(s):  
Protein Synthesis ◽  
Primary Tumour ◽  
Experimental Period ◽  
Whole Body ◽  
Tumour Resection ◽  
Surgical Removal ◽  
Protein Breakdown ◽  
Nitrogen Flux ◽  
Body Protein ◽  
Before And After

1. The rate of whole-body nitrogen flux; protein synthesis and protein breakdown were measured in patients with colorectal cancer (Dukes A—C) just before and 12 weeks after surgical removal of the tumour. The rates were determined from the urinary excretion of 15N in ammonia and in urea over a 9 h period after an oral dose of [15N]glycine. 2. The food intake during the 2 study days was identical for individual patients. The amount each received was determined from measurement of their intake of food ad libitum on the day preceding the pre-operative study and was consumed in six equal portions every 2 h during the experimental period. 3. No significant differences in the rates of nitrogen flux, protein synthesis and protein breakdown were found before and after tumour resection, whether calculated from the excretion of 15N in ammonia or in urea. Some changes in flux, both increases and decreases, were observed in individual patients after tumour removal but these could not be related to classification of the tumour, or to the presence of pre-operative anorexia or weight loss. 4. The results suggest that the primary tumour itself does not alter the overall rate of protein metabolism in the whole body.

Prolonged bed rest decreases skeletal muscle and whole body protein synthesis

1996 ◽  
Vol 270 (4) ◽  
pp. E627-E633 ◽  
Author(s):  
A. A. Ferrando ◽  
H. W. Lane ◽  
C. A. Stuart ◽  
J. Davis-Street ◽  
R. R. Wolfe
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Bed Rest ◽  
Whole Body ◽  
Protein Breakdown ◽  
Skeletal Muscle Protein ◽  
Model Calculations ◽  
Body Protein

We sought to determine the extent to which the loss of lean body mass and nitrogen during inactivity was due to alterations in skeletal muscle protein metabolism. Six male subjects were studied during 7 days of diet stabilization and after 14 days of stimulated microgravity (-6 degrees bed rest). Nitrogen balance became more negative (P < 0.03) during the 2nd wk of bed rest. Leg and whole body lean mass decreased after bed rest (P < 0.05). Serum cortisol, insulin, insulin-like growth factor I, and testosterone values did not change. Arteriovenous model calculations based on the infusion of L-[ring-13C6]-phenylalanine in five subjects revealed a 50% decrease in muscle protein synthesis (PS; P < 0.03). Fractional PS by tracer incorporation into muscle protein also decreased by 46% (P < 0.05). The decrease in PS was related to a corresponding decrease in the sum of intracellular amino acid appearance from protein breakdown and inward transport. Whole body protein synthesis determined by [15N]alanine ingestion on six subjects also revealed a 14% decrease (P < 0.01). Neither model-derived nor whole body values for protein breakdown change significantly. These results indicate that the loss of body protein with inactivity is predominantly due to a decrease in muscle PS and that this decrease is reflected in both whole body and skeletal muscle measures.

Effect of tumor necrosis factor on substrate and amino acid kinetics in conscious dogs

1994 ◽  
Vol 266 (6) ◽  
pp. E936-E945 ◽  
Author(s):  
Y. Sakurai ◽  
X. J. Zhang ◽  
R. R. Wolfe
Keyword(s):  
Amino Acid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Glucose Production ◽  
Conscious Dogs ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Period 2 ◽  
Necrosis Factor

Two groups of conscious dogs were studied using isotopic tracer techniques to test the hypothesis that tumor necrosis factor (TNF) affects glucose production, lipolysis, amino acid, and protein kinetics. [1-13C]leucine, [15N2]urea, [6,6-2H2]glucose, and [2H5]glycerol were infused to determine the leucine, urea, glucose, and lipid kinetics, and NaH14CO3 was infused to determine the rate of CO2 production. In one group, after a 2-h basal period (period 1), recombinant human TNF was infused (prime, 2.5 micrograms/kg; constant, 62.5 ng.kg-1.min-1) for 2 h (period 2; group 1, n = 15). Group 2 received saline rather than TNF in period 2 (n = 3). TNF infusion caused a significant increase in endogenous glucose production, a significant increase in glucose clearance rate, and a decrease in glycerol flux. Although TNF infusion did not change leucine flux, leucine oxidation increased by 49% (P < 0.0001), and nonoxidative leucine disappearance decreased during TNF infusion by 13% (P < 0.0001). TNF infusion also caused a significant increase (18%) in endogenous urea production. TNF significantly increased plasma glucagon concentration. We conclude that TNF causes a shift toward carbohydrate metabolism and stimulates the oxidation of amino acids. Whereas whole body protein breakdown is not affected by TNF, protein synthesis is impaired, leading to an increase in net protein breakdown.

Muscle wasting in emphysema

1988 ◽  
Vol 75 (4) ◽  
pp. 415-420 ◽  
Author(s):  
W. L. Morrison ◽  
J. N. A. Gibson ◽  
C. Scrimgeour ◽  
M. J. Rennie
Keyword(s):  
Protein Synthesis ◽  
Protein Turnover ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Myofibrillar Protein ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Net Protein

1. We have investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indicators of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with emphysema and in 11 healthy controls. Whole-body protein turnover was measured using l-[1-13C]leucine. 2. Leg efflux of tyrosine was increased by 47% in emphysematous patients compared with normal control subjects, but 3-methylhistidine efflux was not significantly altered. 3. In emphysema, whole-body leucine flux was normal, whole-body leucine oxidation was increased, and whole-body protein synthesis was depressed. 4. These results indicate that the predominant mechanism of muscle wasting in emphysema is a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.

Glucose and insulin administration while maintaining normoglycemia inhibits whole body protein breakdown and synthesis after cardiac surgery

2014 ◽  
Vol 117 (11) ◽  
pp. 1380-1387 ◽  
Author(s):  
Roupen Hatzakorzian ◽  
Dominique Shum-Tim ◽  
Linda Wykes ◽  
Ansgar Hülshoff ◽  
Helen Bui ◽  
...  
Keyword(s):  
Amino Acids ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Whole Body ◽  
Control Group ◽  
Protein Breakdown ◽  
Body Protein ◽  
Cabg Surgery ◽  
Insulin Group ◽  
Endogenous Glucose

We investigated the effect of insulin administered as part of a hyperinsulinemic-normoglycemic clamp on protein metabolism after coronary artery bypass grafting (CABG) surgery. Eighteen patients were studied, with nine patients in the control group receiving standard metabolic care and nine patients receiving insulin (5 mU·kg−1·min−1). Whole body glucose production, protein breakdown, synthesis, and oxidation were determined using stable isotope tracer kinetics (l-[1-13C]leucine, [6,6-2H2]glucose) before and 6 h after the procedure. Plasma amino acids, cortisol, and lactate were also measured. Endogenous glucose production (preoperatively 10.0 ± 1.6, postoperatively 3.7 ± 2.5 μmol·kg−1·min−1; P = 0.0001), protein breakdown (preoperatively 105.3 ± 9.8, postoperatively 85.2 ± 9.2 mmol·kg−1·h−1; P = 0.0005) and synthesis (preoperatively 88.7 ± 8.7, postoperatively 72.4 ± 8.4 mmol·kg−1·h−1; P = 0.0005) decreased in the presence of hyperinsulinemia, whereas both parameters remained unchanged in the control group. A positive correlation between endogenous glucose production and protein breakdown was observed in the insulin group ( r2 = 0.385). Whole body protein oxidation and balance decreased after surgery in patients receiving insulin without reaching statistical significance. In the insulin group the plasma concentrations of 13 of 20 essential and nonessential amino acids decreased to a significantly greater extent than in the control group. In summary, supraphysiological hyperinsulinemia, while maintaining normoglycemia, decreased whole body protein breakdown and synthesis in patients undergoing CABG surgery. However, net protein balance remained negative.

The Anabolic Effect of Epidural Blockade Requires Energy and Substrate Supply

2002 ◽  
Vol 97 (4) ◽  
pp. 943-951 ◽  
Author(s):  
Thomas Schricker ◽  
Linda Wykes ◽  
Leopold Eberhart ◽  
Ralph Lattermann ◽  
Louise Mazza ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Synthesis ◽  
Glucose Production ◽  
Whole Body ◽  
Body Protein ◽  
Epidural Blockade ◽  
Thoracic Epidural ◽  
Parenteral Alimentation ◽  
Infusion Study ◽  
Intravenous Analgesia

Background The authors examined the hypothesis that continuous thoracic epidural blockade with local anesthetic and opioid, in contrast to patient-controlled intravenous analgesia with morphine, stimulates postoperative whole body protein synthesis during combined provision of energy (4 mg x kg(-1) x min(-1) glucose) and amino acids (0.02 ml x kg(-1) x min(-1) Travasol 10%, equivalent to approximately 2.9 g x kg(-1) x day(-1)). Methods Sixteen patients were randomly assigned to undergo a 6-h stable isotope infusion study (3 h fasted, 3 h feeding) on the second day after colorectal surgery performed with or without perioperative epidural blockade. Protein synthesis, breakdown and oxidation, glucose production, and clearance were measured by L-[1-(13)C]leucine and [6,6-(2)H(2) ]glucose. Results Epidural blockade did not affect protein and glucose metabolism in the fasted state. Parenteral alimentation decreased endogenous protein breakdown and glucose production to the same extent in both groups. Administration of glucose and amino acids was associated with an increase in whole body protein synthesis that was modified by the type of analgesia, i.e., protein synthesis increased by 13% in the epidural group (from 93.3 +/- 16.6 to 104.5 +/- 11.1 micromol x kg(-1) x h(-1) ) and by 4% in the patient-controlled analgesia group (from 90.0 +/- 27.1 to 92.9 +/- 14.8 micromol x kg(-1) x h(-1);P = 0.054). Conclusions Epidural blockade accentuates the stimulating effect of parenteral alimentation on whole body protein synthesis.

Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise

1996 ◽  
Vol 81 (5) ◽  
pp. 2034-2038 ◽  
Author(s):  
Kevin D. Tipton ◽  
Arny A. Ferrando ◽  
Bradley D. Williams ◽  
Robert R. Wolfe
Keyword(s):  
Protein Synthesis ◽  
Resistance Training ◽  
Endurance Exercise ◽  
Protein Metabolism ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Muscle Protein Metabolism

Tipton, Kevin D., Arny A. Ferrando, Bradley D. Williams, and Robert R. Wolfe. Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise. J. Appl. Physiol. 81(5): 2034–2038, 1996.—There is little known about the responses of muscle protein metabolism in women to exercise. Furthermore, the effect of adding resistance training to an endurance training regimen on net protein anabolism has not been established in either men or women. The purpose of this study was to quantify the acute effects of combined swimming and resistance training on protein metabolism in female swimmers by the direct measurement of muscle protein synthesis and whole body protein degradation. Seven collegiate female swimmers were each studied on four separate occasions with a primed constant infusion of ring-[13C6]phenylalanine (Phe) to measure the fractional synthetic rate (FSR) of the posterior deltoid and whole body protein breakdown. Measurements were made over a 5-h period at rest and after each of three randomly ordered workouts: 1) 4,600 m of intense interval swimming (SW); 2) a whole body resistance-training workout with no swimming on that day (RW); and 3) swimming and resistance training combined (SR). Whole body protein breakdown was similar for all treatments (0.75 ± 0.04, 0.69 ± 0.03, 0.69 ± 0.02, and 0.71 ± 0.04 μmol ⋅ min−1 ⋅ kg−1for rest, RW, SW, and SR, respectively). The FSR of the posterior deltoid was significantly greater ( P< 0.05) after SR (0.082 ± 0.015%/h) than at rest (0.045 ± 0.006%/h). There was no significant difference in the FSR after RW (0.048 ± 0.004%/h) or SW (0.064 ± 0.008%/h) from rest or from SR. These data indicate that the combination of swimming and resistance exercise stimulates net muscle protein synthesis above resting levels in female swimmers.

Amino acid metabolism after intense exercise

1990 ◽  
Vol 258 (2) ◽  
pp. E249-E255 ◽  
Author(s):  
J. T. Devlin ◽  
I. Brodsky ◽  
A. Scrimgeour ◽  
S. Fuller ◽  
D. M. Bier
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Protein Degradation ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Recovery Period ◽  
Whole Body ◽  
Protein Breakdown ◽  
Body Protein ◽  
Leucine Oxidation

We studied postexercise amino acid metabolism, in the whole body and across the forearm. Seven volunteers were infused with L-[alpha-15N]lysine and L-[1-13C]-leucine twice [one time during 3 h after cycle exercise (75% VO2max), and one time in the resting state]. Whole body protein breakdown was estimated from dilution of L-[alpha-15N]lysine and L-[1-13C]ketoisocaproic acid (KIC) enrichments in plasma. Leucine oxidation was calculated from 13CO2 enrichments in expired air. Whole body protein breakdown was not increased above resting levels during the recovery period. Leucine oxidation was decreased after exercise (postexercise 13 +/- 2.3 vs. resting 19 +/- 3.2 mumol.kg-1.h-1; P less than 0.02), while nonoxidative leucine disposal was increased (115 +/- 6.1 vs. 103 +/- 5.6 micrograms.kg-1.min-1; P less than 0.02). After exercise, forearm net lysine balance was unchanged (87 +/- 25 vs. 93 +/- 28 nmol.100 ml-1.min-1), but there were decreases in forearm muscle protein degradation (219 +/- 51 vs. 356 +/- 85 nmol.100 ml-1.min-1; P less than 0.05) and synthesis (132 +/- 41 vs. 255 +/- 69 nmol.100 ml-1.min-1; P less than 0.01). In conclusion, after exercise 1) whole body protein degradation is not increased, 2) leucine disposal is directed away from oxidative and toward nonoxidative pathways, 3) forearm protein synthesis is decreased. Postexercise increases in whole body protein synthesis occur in tissues other than nonexercised muscle.

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