Effects of therapeutic percutaneous electrical stimulation of atrophic human quadriceps on muscle composition, protein synthesis and contractile properties

The effects of percutaneous electrical stimulation (70 V, 300 microseconds pulses at 30 Hz) on muscle composition and rate of protein synthesis were studied in seven patients with quadriceps atrophy secondary to unilateral osteoarthritis of the knee (stimulated group). Quadriceps were stimulated on the affected side for 1 h per day. The results were compared to those from seven patients who did not use a muscle stimulator (control group), in whom muscle biopsy at surgery provided evidence of wasting of tissue protein on the side of osteoarthritis (normal leg 608 +/- 266 micrograms protein micrograms-1 DNA, affected leg 256 +/- 100 micrograms protein micrograms-1 DNA, means +/- SD, P less than 0.05; type I fibre diameters: normal 53.2 +/- 6.7 microns, affected 43.8 +/- 4.0 microns, P less than 0.05). In patients who had received stimulation there was no residual difference between the legs in either muscle protein concentration (normal 411 +/- 168 micrograms protein micrograms-1 DNA, affected 373 +/- 112 micrograms protein micrograms-1 DNA) or fibre diameter (type I diameters: normal 56.1 +/- 7.8 microns, affected 58.0 +/- 10.7 microns). Stimulation did not influence the ratios of muscle force elicited by acute stimulation at 20 and 50 Hz (normal 75 +/- 15%, affected 79 +/- 15%), or rates of muscle relaxation (percentage losses of tetanic force 10 ms-1: normal 7.66 +/- 1.2%, affected 8.67 +/- 2.2%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle protein synthesis in patients with rheumatoid arthritis: effect of chronic corticosteroid therapy on prostaglandin F2α availability

Using stable-isotope techniques, we measured rates of quadriceps muscle protein synthesis in twelve women with sero-positive rheumatoid arthritis. The results were compared to those from the normal limb of seven women with unilateral osteoarthritis of the knee. Six patients had never received corticosteroid immuno-suppression, but the other six had taken an average of 8 mg Prednisolone per day for 9 years. Quadriceps atrophy was present in both sets of patients with rheumatoid arthritis (normal legs 444 +/- 182, rheumatoid 190 +/- 40, rheumatoid + steroid 300 +/- 110 micrograms protein/micrograms DNA, means +/- SD, both P less than 0.001). Muscle protein synthesis, calculated by comparing the incorporation of 13C-leucine into biopsy samples taken after an 8 h L-[1-13C] leucine infusion with the time averaged enrichment of blood alpha-ketoisocaproate, was 0.056 +/- 0.005% h-1 in the patients not receiving steroids compared with 0.050 +/- 0.02% h-1 in normals (P greater than 0.05) indicating that muscular atrophy was primarily due to an increase in rate of muscle protein breakdown. Intra-muscular PGE2 concentration was increased in these patients (rheumatoid 0.12 +/- 0.06 ng mg-1 tissue, normals 0.06 +/- 0.03 ng mg-1 tissue, P less than 0.05). Patients taking corticosteroids had a markedly depressed rate of muscle protein synthesis (0.035 +/- 0.008% h-1, P less than 0.05) and reduced intra-muscular PGF 2 alpha concentration (P less than 0.01). We conclude that steroid therapy significantly influences the mechanism of skeletal muscle atrophy in patients with rheumatoid arthritis.     

Rate of protein synthesis in skeletal muscle of normal man and patients with muscular dystrophy: a reassessment

1. Quadriceps muscle protein synthetic rate has been determined in healthy subjects in the post-absorptive (n = 18) and fed (n = 10) states and in patients with a variety of myopathies, by analysis of the enrichment of serial muscle biopsies taken during primed continuous infusion of L-[1-13C]leucine. 2. Quadriceps protein synthetic rates in normal subjects were (mean +/- SD) 0.046 +/- 0.012 and 0.075 +/- 0.014%/h in the post-absorptive and fed states respectively. These results are significantly lower than we previously reported (M. J. Rennie et al., Clinical Science, 1982, 63, 519-523 [1]) but show the same relative differences of direction and magnitude, confirming the effects of feeding previously reported. In patients with muscular dystrophy, muscle protein synthetic rate was, as previously reported [1], much lower in the fed state than in normal subjects. A new finding is that for patients with myotonic dystrophy the rate is also depressed in the post-absorptive state. 3. We suggest that the present estimates in post-absorptive and fed normal subjects be used as reference values for quadriceps mixed muscle protein synthetic rate.     

Long-lasting unilateral muscle wasting and weakness following injury and immobilisation

Quadriceps strength and size was measured in a small group of subjects (n = 7) 1 to 5 years after full mobilisation following some form of unilateral lower limb trauma. The mean maximum voluntary isometric force (MVC) was significantly lower for the injured (I) compared to the uninjured (UI) leg (369 N +/- 139 vs. 535 N +/- 131, p less than 0.01). Electrical stimulation superimposed on the voluntary contractions demonstrated that all subjects were able to maximally activate the quadriceps of both legs. Mean quadriceps cross-sectional area (CSA) was significantly lower in the I (64 cm2 +/- 12.8) compared to the UI leg (80 +/- 12.8, p less than 0.01). One subject with marked unilateral weakness and wasting took part in a 3-month strength training study for the injured leg. After training the I/UI ratio had been restored to nearly 100% (94% MVC; 88% CSA). These results would suggest that longer and more intensive physiotherapy is required in the immediate post-injury period to restore muscle strength and size to severely atrophied muscle.     

Muscle and bone in paraplegic patients, and the effect of functional electrical stimulation

1. Four paraplegic men volunteered for an exercise programme in which their paralysed quadriceps muscles were stimulated by means of computer-regulated electrical impulses applied through external electrodes. The first exercise regimen consisted of leg raising against a graded load, and during the second regimen exercise took the form of cycling on a modified bicycle ergometer. Each subject exercised five times weekly for 10 weeks during the first regimen and 32 weeks during the second regimen. 2. Whole-body protein turnover determined by L-[1-13C]leucine during feeding remained constant during both exercise regimens, when expressed either in terms of body weight or fat-free mass derived from measurements of total body potassium. 3. Quadriceps muscle protein synthetic rate increased during the study, from 0.0712 to 0.0985%/h (P less than 0.05), as did quadriceps muscle area assessed by computed tomography. 4. Bone mineral content for lumbar vertebrae was normal in all four patients, but for the femoral mid-shaft bone mineral content averaged only 66% of normal for three of the patients. Trabecular bone density in the distal tibia ranged from normal to 2% of normal for the men with the shortest and longest periods of disability, respectively. No changes in bone mineral content or bone density occurred during the exercise period.     

The effect of amino acid infusion on leg protein turnover assessed by L-[15N]phenylalanine and L-[1-13C]leucine exchange

A stable isotope technique depending on the use of [15N]phenylalanine and [1-13C]leucine to assess exchange was utilized to measure the components of protein turnover of the human leg and the effects of amino acid infusion. Eight healthy subjects (28.5 +/- 2.5 years) were studied when post-absorptive in the basal state and again during infusion of a mixed amino acid solution (55 g l-1, 1.52 ml kg-1 h-1). During the basal period leucine oxidation by the leg was 4.4 +/- 2.0 nmol 100 g-1 min-1 and this increased threefold during amino acid infusion (13.6 +/- 3.1 nmol 100 g-1 min-1, mean +/- SEM, P = 0.003). Amino acid infusion abolished the net negative balance between incorporation of leucine into, and release from, protein (basal, -31.8 +/- 5.8; during infusion, +3.1 +/- 7.1 nmol 100 g-1 P = 0.001). Phenylalanine exchange showed a similar pattern (basal, -13.7 +/- 1.8; during infusion, -0.8 +/- 3.0 nmol 100 g-1 min-1, P = 0.003). Basal entry of leucine into leg protein (i.e. protein synthesis) was 70.0 +/- 10.8 nmol 100 g-1 min-1 and this increased during amino acid infusion to 87.3 +/- 14.1 nmol 100 g-1 min-1 (P = 0.11). Phenylalanine entry to protein also increased with amino acid infusion (29.1 +/- 4.5 vs. 38.3 +/- 5.8 nmol 100 g-1 min-1, P = 0.09). Release from protein of leucine (101.8 +/- 9.1 vs. 84.2 +/- 9.1 nmol 100 g-1 min-1, P = 0.21) and of phenylalanine (42.8 +/- 4.2 vs. 39.1 +/- 4.2 nmol 100 g-1 min-1, P = 0.50) was unchanged by amino acid infusion. The results suggest that, in the post-absorptive state in man, infusion of mixed amino acids, without additional energy substrates; reverses negative amino acid balance by a mechanism which includes stimulation of muscle protein synthesis but which does not alter protein breakdown. Interpretation of the results obtained concurrently on whole-body protein turnover suggests that the increase in muscle protein synthesis contributes substantially to the whole-body increase, but the fall in whole-body breakdown with exogenous amino acids is independent of changes in muscle.     

Small-intestinal mucosal protein synthesis and whole-body protein turnover in alcoholic liver disease

We used stable-isotope-labelled amino acids to measure the effects of alcoholic liver disease (ALD) on whole-body protein turnover and small-intestinal mucosal protein synthesis. Groups comprising eight patients with ALD and eight healthy control subjects were studied. They received primed, continuous intravenous infusions of L-[1-(13)C]leucine after an overnight fast; after 4 h, duodenal biopsies were obtained via endoscopy. Protein synthesis was calculated from protein labelling relative to intracellular leucine enrichment. Rates of duodenal mucosal protein synthesis were 2. 58+/-0.32%.h(-1) (mean+/-S.D.) in the normal subjects and 2.04+/-0. 18%.h(-1) in the ALD patients (P<0.003), despite the fact that the protein synthetic capacity (microgram of RNA/mg of protein) was higher in ALD patients (160+/-14 compared with 137+/-6 microgram/mg; P<0.003). The mucosal cell size (protein/DNA ratio) was lower in ALD patients (9.23+/-0.91 compared with 13+/-2.2 microgram/mg; P<0.002). Although the mean rates of whole-body protein turnover were not significantly different between the two groups (204+/-18 and 196+/-44 micromol leucine.h(-1).kg(-1) for ALD and control subjects respectively), there was, in the ALD patients, an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the severity of ALD; furthermore, there was a direct relationship between the rate of whole-body protein turnover and the severity of ALD. Thus there was an inverse relationship between the rate of small-intestinal mucosal protein synthesis and the rate of whole-body protein turnover in ALD patients, which was not seen in the normal subjects.     

Increase in anterior tibialis muscle protein synthesis in healthy man during mixed amino acid infusion: studies of incorporation of [1-13C]leucine

1. Anterior tibial muscle protein synthesis in seven healthy postabsorptive men was determined from increases in muscle protein bound leucine enrichment during a primed continuous infusion of L-[1-13C]leucine. Biopsies were taken 30 min after the beginning of leucine infusion (when plasma 13C enrichment was steady), 240 min later during continued fasting and again after 240 min of infusion of a mixed amino acid solution which increased plasma total amino acid concentrations by 37%. The mean enrichment of 13C in plasma alpha-ketoisocaproate was used as an index of the enrichment of the precursor pool for leucine metabolism. 2. Anterior tibial muscle mixed protein synthetic rate during fasting was 0.055 (SD 0.008)%/h and this increased by an average of 35% during infusion of mixed amino acid to 0.074 (SD 0.021)%/h (P less than 0.05). 3. Whole-body protein breakdown (expressed as the rate of endogenous leucine appearance in plasma) was 121 (SD 8) mumol h-1 kg-1 during fasting and decreased (P less than 0.01) by an average of 12% during amino acid infusion. Leucine oxidation was 18 (SD 3) mumol h-1 kg-1 during fasting and increased (P less than 0.001) by 89% during amino acid infusion. Whole-body protein synthesis (non-oxidative leucine disappearance) was 104 (SD 6) mumol h-1 kg-1 during fasting and rose by 13% (P less than 0.001) during mixed amino acid infusion. 4. 13C enrichment of muscle free leucine was only 61 (SD 19)% of that in plasma alpha-ketoisocaproate and this increased to 74 (SD 16)% (P less than 0.02) during mixed amino acid infusion. 5. The results suggest that increased availability of amino acids reverses whole-body protein balance from negative to positive and a major component of this is the increase in muscle protein synthesis.     

Thigh composition in young and elderly men determined by computed tomography

Summary. Computed tomography (CT) was used to quantify components of the thigh in young (n= 13) and elderly (n= 11) men. Cross-sectional areas (CSA) of the total limb, total muscle plus bone, quadriceps compartment, hamstring compartment and bone were measured at each of five scan sites along the length of the thigh. Non-muscle tissue (NMT) areas within the muscle compartments were measured using changes in density based on Hounsfield units. Skin plus subcutaneous fat areas and quadriceps and hamstring lean muscle areas were calculated by subtraction. Geometric formulae were used to calculate related volumes for each thigh component. Volumes were also predicted from regression equations employing thigh length and component CSA from single mid-limb CT scans. The results showed that while total thigh CSA was not different in elderly men, they had significantly smaller total muscle plus bone (13-0%), and quadriceps (26.4%), and hamstring (17.9%) muscle areas. The elderly men also had significantly greater CSA for skin plus subcutaneous fat (37-6%), and for NMT in the quadriceps (59.4%) and hamstring (127.3%) muscle compartments. These results suggest that comparisons of relative leg muscle strength between young and elderly men may be misleading due to the decrease in actual muscle tissue associated with ageing. Appropriate quantification of muscle size and CSA must be carried out before such comparisons can be meaningful.     

Component characteristics of thigh muscle volume in young and older healthy men

The purpose of this study was to compare the component characteristics of thigh muscle volume in Japanese young and older men. The subjects in both young (YM, n = 15) and older (OM, n = 13) men were physically active (performed aerobic-type exercise 1-3 times per week), but none of the subjects had regularly participated in resistance training for a minimum of 3 years prior to the study. Contiguous transverse magnetic resonance imaging (1.5-T scanner) images were obtained from the thigh, and total and individual (quadriceps, hamstrings and adductors) muscle volumes were calculated by multiplying the muscle cross-sectional area (CSA) by slice thickness and the total number of slices. Muscle length and average muscle CSA (muscle volume divided by muscle length) were determined for each muscle. Maximum voluntary isometric (MVC) knee extension and flexion strength were measured, and muscle quality was defined as MVC per unit average muscle CSA (MVC/CSA). Quadriceps muscle volume and average CSA were, respectively, 20% and 16% lower (P < 0.05) in the OM than in the YM, while hamstrings and adductors muscle volumes and average CSA were similar in both groups. Knee extension and flexion MVC were lower (P < 0.05) in the OM than in the YM. Knee extensor MVC/CSA was similar in the two groups, while knee flexor MVC/CSA was lower (P < 0.05) in the OM than in the YM. Our results suggest that age-related thigh muscle volume loss is muscle specific, in that greater quadriceps muscle loss was found in the older group.     

Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.

Because intravenous infusion of beta-hydroxybutyrate (beta-OHB) has been reported to decrease urinary nitrogen excretion, we investigated in vivo metabolism of leucine, an essential amino acid, using L-[1-13C]leucine as a tracer during beta-OHB infusion. Leucine flux during beta-OHB infusion did not differ from leucine flux during normal saline infusion in nine normal subjects, whereas leucine oxidation decreased 18-41% (mean = 30%) from 18.1 +/- 1.1 mumol.kg-1.h-1 (P less than 0.01), and incorporation of leucine into skeletal muscle protein increased 5-17% (mean = 10%) from 0.048 + 0.003%/h (P less than 0.02). Since blood pH during beta-OHB infusion was higher than the pH during saline infusion, we performed separate experiments to study the effect of increased blood pH on leucine kinetics by infusing sodium bicarbonate intravenously. Blood pH during sodium bicarbonate infusion was similar to that observed during the beta-OHB infusion, but bicarbonate infusion had no effect on leucine flux or leucine oxidation. We conclude that beta-OHB decreases leucine oxidation and promotes protein synthesis in human beings.     

Progressive resistance exercise training of the hypotrophic quadriceps muscle in man. The effects on morphology, size and function as well as the influence of duration of effort

The effects of progressive resistance exercise (PRE) training for 4 weeks on the hypotrophic quadriceps muscle were investigated in 23 young healthy male soccer players, who had been immobilized in a plaster cast 4-6 weeks after knee ligament injuries. The subjects were allocated to two training regimes where the injured leg was trained for periods of varying duration, whereas the intensity and frequency of exercise were alike in the two groups. However no significant differences were detected between the two training groups. In the whole material the lean thigh volume of the injured leg increased from 4.09 to 4.47 litres (p less than 0.001), whereas the fat component of the thigh was unchanged. The dynamic strength (1 RM) of the injured leg increased from 14.0 kg to 27.0 kg and amounted to 87% of the control leg after 4 weeks of training. At this time the maximum isometric strength amounted to 114 Nm, which was 63% of strength in the control leg. Succinate dehydrogenase (SDH) in homogenates of muscle biopsy sample increased (i.e. 20%, p less than 0.05) to the same level as found in the control leg. No changes in phosphofructokinase (PFK) were observed. The type I fibre distribution was lower in the immobilized leg than in the control leg. These results indicate that, following muscular hypotrophy resulting from 4-6 weeks of immobilization, dynamic exercise can restore the oxidative potential, whereas the size and strength are only partly recovered.     

Skeletal muscle and whole-body protein turnover in cirrhosis

1. We investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indices of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with cirrhosis and in 11 healthy control subjects. Whole-body protein turnover was also measured using L-[1-13C]leucine. 2. Leg efflux of tyrosine was 45% greater in cirrhotic patients than in normal control subjects [-6.5(1.4 to -19.1) vs -4.2(-2.2 to -7.7) mumol min-1 100 mg-1 of leg, median (range), P less than 0.025]. 3-Methylhistidine efflux was not significantly altered. 3. In cirrhosis, whole-body leucine flux was normal but whole-body leucine oxidation was elevated so that whole-body protein synthesis was depressed by 17%. 4. The results indicate the predominant mechanism of muscle wasting in cirrhosis to be a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.     

Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man.

Although insulin stimulates protein synthesis and inhibits protein breakdown in skeletal muscle in vitro, the actual contribution of these actions to its anabolic effects in man remains unknown. Using the forearm perfusion method together with systemic infusion of L-[ring-2,6-3H]phenylalanine and L-[1-14C]leucine, we measured steady state amino acid exchange kinetics across muscle in seven normal males before and in response to a 2-h intraarterial infusion of insulin. Postabsorptively, the muscle disposal (Rd) of phenylalanine (43 +/- 5 nmol/min per 100 ml forearm) and leucine (113 +/- 13) was exceeded by the concomitant muscle production (Ra) of these amino acids (57 +/- 5 and 126 +/- 9 nmol/min per dl, respectively), resulting in their net release from the forearm (-14 +/- 4 and -13 +/- 5 nmol/min per dl, respectively). In response to forearm hyperinsulinemia (124 +/- 11 microU/ml), the net balance of phenylalanine and leucine became positive (9 +/- 3 and 61 +/- 8 nmol/min per dl, respectively (P less than 0.005 vs. basal). Despite the marked increase in net balance, the tissue Rd for both phenylalanine (42 +/- 2) and leucine (124 +/- 9) was unchanged from baseline, while Ra was markedly suppressed (to 33 +/- 5 and 63 +/- 9 nmol/min per dl, respectively, P less than 0.01). Since phenylalanine is not metabolized in muscle (i.e., its only fates are incorporation into or release from protein) these results strongly suggest that in normal man, physiologic elevations in insulin promote net muscle protein anabolism primarily by inhibiting protein breakdown, rather than by stimulating protein synthesis.     

The effect of high-resistance training on the strength and cross-sectional area of the human quadriceps

Seventeen volunteers performed unilateral strength-training of the quadriceps with high-resistance, low-repetition, dynamic exercise, thrice weekly for an average of 5 weeks. Both before and after the training period, bilateral measurements were made of isometric quadriceps strength, quadriceps cross-sectional area (by ultrasound scanning), and thigh circumference. There were no significant changes in the untrained thighs. The trained quadriceps increased their isometric strength by more than they changed their cross-sectional area (mean increments = 15% and 6% respectively). Quadriceps hypertrophy was underestimated by measurements of thigh circumference and could not be predicted from them. We conclude that studies of localized muscle growth require direct measurements of the size of the muscle(s) concerned. Nevertheless, these may still underestimate the improvements in strength produced by high-resistance training.     

Comparison of two electrical stimulation protocols on quadriceps muscle after anterior cruciate ligament surgery. Feasability study]

OBJECTIVES: To evaluate the feasibility of a study comparing the effects of two protocols of electrical stimulation of the quadriceps femoris after anterior cruciate ligament surgery. MATERIAL: Seven sportsmen with a mean age of 26 yrs were randomly grouped in two: a 20 Hz stimulated group (4 patients) and a 80 Hz stimulated group (3 patients). After surgery all patients received electrical stimulation of the quadriceps femoris, five days a week, for 12 weeks, and had a standard program of voluntary contractions. The main outcome assessed before and three months after surgery were: quadriceps and hamstring peak torque at 90, 180 and 240 degrees /second, maximal isometric quadriceps at 75 degrees of flexion and muscle and subcutaneous fat volumes of the thigh using MRI. RESULTS: After 12 weeks of rehabilitation, the thigh muscle volume deficit of the operated limb was between 3 and 9% in the 20 Hz stimulated group and between 1 and 2% in the 80 Hz stimulated group. Quadriceps peak torque deficit was less than 30% except for two patients in the 20 Hz stimulated group. Maximal isometric quadriceps deficit of the operated limb was higher than 30% except for two patients in the 20 Hz stimulated group. CONCLUSION: The study showed that comparison of two protocols of electrical stimulation of the quadriceps femoris after anterior cruciate ligament surgery is possible if stimulation period is not more than four weeks.     

Skeletal muscle and whole body protein turnover in thyroid disease

The effects of disturbances of thyroid hormone secretion on leg and whole body amino acid and protein metabolism have been investigated in seven patients with untreated thyrotoxicosis and eight patients with untreated hypothyroidism; the results were compared to those obtained in 11 normal control subjects. After treatment, the patients were restudied. Arterio-venous exchanges of tyrosine and 3-methylhistidine across leg tissue in the post-absorptive state were used as indices of net protein balance and myofibrillar protein breakdown, respectively. Whole body protein turnover was measured using stable isotope labelling techniques with 1-[1-13C] leucine. Efflux of tyrosine from leg tissues was six-fold greater in patients with untreated thyrotoxicosis than in normal control subjects (-19.39 +/- 2.21 vs. -4.20 +/- 0.31 nmol 100 g-1 leg tissue min-1, P less than 0.005, mean +/- SEM), but 3-methyl-histidine efflux was not significantly different (-0.11 +/- 0.03 nmol 100 g-1 leg tissue min-1 vs. 0.14 +/- 0.02 nmol 100 g-1 leg tissue min-1). After treatment, when the thyrotoxic patients became euthyroid, tyrosine efflux was normalized (at -4.94 +/- 0.84 nmol 100 g-1 leg tissue min-1) and 3-methylhistidine efflux was unchanged. In hypothyroid patients, neither tyrosine nor 3-methylhistidine effluxes were significantly different from those in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Skeletal muscle and whole body protein turnover in cardiac cachexia: influence of branched-chain amino acid administration

Muscle protein wasting commonly accompanies severe heart failure. The mechanism of this so-called cardiac cachexia has been investigated in eight patients with an average body weight decrement of 19%, whose results have been compared with those from 11 healthy control subjects. Exchanges of tyrosine and 3-methylhistidine across leg tissue were used as specific indicators of net protein balance and myofibrillar protein breakdown, respectively. Whole body protein turnover was measured using a stable isotope labelling technique with L-[1-13C]leucine as tracer. In patients with cardiac cachexia there were greater values, relative to those values in normal control subjects, of leg efflux of tyrosine (-8.1 +/- 0.6 nmol 100 ml leg tissue-1 min-1 vs. -4.2 +/- 0.3 nmol 100 ml-1 min-1 (P less than 0.01) and of 3-methylhistidine (-0.8 +/- 0.1 nmol 100 ml leg tissue-1 min-1 vs. -0.1 +/- 0.02 nmol 100 ml-1 min-1 (P less than 0.005), mean +/- SEM). The results suggest that in patients with cardiac cachexia the state of net negative protein balance across leg tissue is associated with an increased rate of myofibrillar protein breakdown. In cardiac cachexia, neither efflux of tyrosine (-8.4 +/- 0.7 nmol 100 ml leg tissue-1 min-1) nor of 3-methylhistidine (-1.0 +/- 0.2 nmol 100 ml leg tissue-1 min-1) were significantly altered by branched-chain amino acid (BCAA) infusion to plasma concentrations of 1300 +/- 14 mumol ml-1, i.e., four times normal plasma values (282 +/- 11 mumol ml-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of insulin and exercise on muscle lipoprotein lipase activity in man and its relation to insulin action.

The effects of exercise and a physiological increase in plasma insulin concentration on muscle lipoprotein lipase activity (mLPLA), leg exchange of glucose, and serum lipoprotein levels were investigated in healthy young men. During euglycemic hyperinsulinemia (n = 7) at 44 mU.liter-1, m-LPLA in non-exercised muscle decreased from 30 +/- 7.4 mU.g-1 wet weight (w.w.) (mean +/- SE) to 19 +/- 3.3 (P less than 0.05). Furthermore, the decrease in m-LPLA correlated closely (r = 0.97, P less than 0.05) with the increase in leg glucose uptake. Moreover, basal m-LPLA correlated with the insulin-induced increase in leg glucose uptake (r = 0.93, P less than 0.05). In the control group (n = 6) in which saline was infused in place of insulin and glucose, m-LPLA in nonexercised muscle did not change with time. No change in m-LPLA was observed immediately after one-legged knee extension exercise, but 4 h after exercise m-LPLA was higher (P less than 0.05) in the exercised thigh (47 +/- 17.8 mU.g-1 w.w.) compared with the contralateral nonexercised thigh (29 +/- 6.3 mU.g-1 w.w.). This difference was not found 8 h after exercise. The triacylglycerol content of serum lipoproteins decreased during insulin infusion. It is concluded that in contrast to the effect on adipose tissue, physiological concentrations of insulin decrease m-LPLA in proportion to the effect of insulin on muscle glucose uptake, while muscle contractions cause a local, delayed, and transient increase in m-LPLA. Further-more, basal m-LPLA is an indicator of muscle insulin sensitivity.     

Measurement of protein synthesis in human skeletal muscle: further investigation of the flooding technique.

1. The rate of protein synthesis in quadriceps muscle of healthy subjects estimated from the incorporation of L-[1-13C]leucine given by continuous infusion was 1.1%/day. The estimate of protein synthesis from the incorporation of a flooding amount of labelled leucine was 1.8%/day (SD 0.65). The possibility that the higher rate obtained with the flooding technique arose from stimulation of protein synthesis by the large amount of leucine is unlikely. 2. The same rate of protein synthesis (1.7%/day, SD 0.3) was obtained with a flooding amount (0.05 g/kg) of a different amino acid, L-[1-13C]phenylalanine, as was obtained with leucine. 3. Incorporation of L-[1-13C]phenylalanine was not affected by simultaneous injection of leucine (1.7%/day, SD 0.7) or valine (1.6%/day, SD 0.4). 4. Protein synthesis, assessed in a completely different way from the proportion of polyribosomes isolated from the skeletal muscle, was unaltered by the injection of 0.05 g of L-leucine/kg (44.6%, SD 8.5 versus 43.8%, SD 7.7). 5. Good agreement in estimates of protein synthesis was observed in subjects in whom both legs were measured with both L-[1-13C]leucine (mean difference 0.16%/day) and L-[1-13C]phenylalanine (mean difference 0.2%/day).