Skeletal muscle myofibrillar protein metabolism in heart failure: relationship to immune activation and functional capacity

Chronic heart failure is characterized by changes in skeletal muscle that contribute to physical disability. Most studies to date have investigated defects in skeletal muscle oxidative capacity. In contrast, less is known about how heart failure affects myofibrillar protein metabolism. Thus we examined the effect of heart failure on skeletal muscle myofibrillar protein metabolism, with a specific emphasis on changes in myosin heavy chain (MHC) protein content, synthesis, and isoform distribution in 10 patients with heart failure (63 +/- 3 yr) and 11 controls (70 +/- 3 yr). In addition, we examined the relationship of MHC protein metabolism to inflammatory markers and physical function. Although MHC and actin protein content did not differ between groups, MHC protein content decreased with increasing disease severity in heart failure patients (r = -0.748, P < 0.02), whereas actin protein content was not related to disease severity. No difference in MHC protein synthesis was found between groups, and MHC protein synthesis rates were not related to disease severity. There were, however, relationships between C-reactive protein and both MHC protein synthesis (r = -0.442, P = 0.05) and the ratio of MHC to mixed muscle protein synthesis (r = -0.493, P < 0.03). Heart failure patients showed reduced relative amounts of MHC I (P < 0.05) and a trend toward increased MHC IIx (P = 0.06). In regression analyses, decreased MHC protein content was related to decreased exercise capacity and muscle strength in heart failure patients. Our results demonstrate that heart failure affects both the quantity and isoform distribution of skeletal muscle MHC protein. The fact that MHC protein content was related to both exercise capacity and muscle strength further suggests that quantitative alterations in MHC protein may have functional significance.     

Aging, muscle fiber type, and contractile function in sprint-trained athletes.

Biopsy samples were taken from the vastus lateralis of 18- to 84-yr-old male sprinters (n = 91). Fiber-type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content were identified using ATPase histochemistry and SDS-PAGE. Specific tension and maximum shortening velocity (V(o)) were determined in 144 single skinned fibers from younger (18-33 yr, n = 8) and older (53-77 yr, n = 9) runners. Force-time characteristics of the knee extensors were determined by using isometric contraction. The cross-sectional area of type I fibers was unchanged with age, whereas that of type II fibers was reduced (P < 0.001). With age there was an increased MHC I (P < 0.01) and reduced MHC IIx isoform content (P < 0.05) but no differences in MHC IIa. Specific tension of type I and IIa MHC fibers did not differ between younger and older subjects. V(o) of fibers expressing type I MHC was lower (P < 0.05) in older than in younger subjects, but there was no difference in V(o) of type IIa MHC fibers. An aging-related decline of maximal isometric force (P < 0.001) and normalized rate of force development (P < 0.05) of knee extensors was observed. Normalized rate of force development was positively associated with MHC II (P < 0.05). The sprint-trained athletes experienced the typical aging-related reduction in the size of fast fibers, a shift toward a slower MHC isoform profile, and a lower V(o) of type I MHC fibers, which played a role in the decline in explosive force production. However, the muscle characteristics were preserved at a high level in the oldest runners, underlining the favorable impact of sprint exercise on aging muscle.     

The influence of 5 weeks of ULLS and resistance exercise on vastus lateralis and soleus myosin heavy chain distribution

We examined the distribution of the myosin heavy chain (MHC) isoforms (I, IIa, IIx) of the leg muscles of three groups of men and women (40 +/- 8y) that completed unilateral lower limb suspension only (ULLS), ULLS plus resistance exercise (ULLS+RE), or RE only (RE) for 5 weeks. Muscle biopsies were obtained pre and post from the vastus lateralis of all three groups and the soleus of the ULLS group. Distributions of all three MHC isoforms in the vastus lateralis were unchanged (p<0.05) from pre to post with ULLS. The soleus muscle, which contained no measurable IIx isoform, was also unchanged (p< 0.05) from pre to post ULLS. These results suggest that the percent distribution of the MHC isoforms per unit muscle protein in both the vastus lateralis and soleus does not change during the first five weeks of simulated microgravity. Further, resistance exercise during five weeks of ULLS or ambulation does not appear to alter the MHC distribution per unit muscle protein of the vastus lateralis.     

Human soleus and vastus lateralis muscle protein metabolism with an amino acid infusion

The calf muscles, compared with the thigh, are less responsive to resistance exercise in ambulatory and bed-rested individuals, apparently due to muscle-specific differences in protein metabolism. We chose to evaluate the efficacy of using amino acids to elevate protein synthesis in the soleus, because amino acids have been shown to have a potent anabolic effect in the vastus lateralis. Mixed muscle protein synthesis in the soleus and vastus lateralis was measured before and after infusion of mixed amino acids in 10 individuals (28 +/- 1 yr). Phosphorylation of ribosomal protein p70 S6 kinase (p70S6K; Thr389) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1; Thr37/46) was also evaluated at rest and after 3 h of amino acid infusion. Basal protein synthesis was similar (P = 0.126), and amino acids stimulated protein synthesis to a similar extent (P = 0.004) in the vastus lateralis (0.043 +/- 0.011%/h) and soleus (0.032 +/- 0.017%/h). Phosphorylation of p70S6K (P = 0.443) and 4E-BP1 (P = 0.192) was not increased in either muscle; however, the soleus contained more total (P = 0.002) and phosphorylated (P = 0.013) 4E-BP1 than the vastus lateralis. These data support the need for further study of amino acid supplementation as a means to compensate for the reduced effectiveness of calf resistance exercise in ambulatory individuals and those exposed to extended periods of unloading. The greater 4E-BP1 in the soleus suggests that there is a muscle-specific distribution of general translational initiation machinery in human skeletal muscle.     

Stimulation of myofibrillar synthesis by exercise is mediated by more efficient translation of mRNA.

Resistance exercises stimulate protein synthesis in human muscle, but the roles of changes in mRNA concentrations and changes in the efficiency of mRNA translation have not been defined. The present study was done to determine whether resistance exercise affects concentrations of total RNA, total mRNA, actin mRNA, or myosin heavy-chain mRNA (total and isoform specific). Eight subjects, 62-75 yr old, performed unilateral knee extensions at 80% of their one-repetition-maximum capacity on days 1, 3, and 6 of the study. On day 7, biopsies of exercised and nonexercised vastus lateralis muscles were obtained. Myofibrillar synthesis was determined by stable- isotope incorporation, and mRNA concentrations were determined by membrane hybridization and PCR-based methods. The exercise stimulated myofibrillar synthesis [30 +/- 6 (SE)%] without affecting RNA or mRNA concentrations. The effect of exercise on protein synthesis in individual subjects did not correlate with the effect on total RNA and mRNA concentrations. These data suggest that the stimulation of myofibrillar synthesis by resistance exercise is mediated by more efficient translation of mRNA.     

No effect of menstrual cycle on myofibrillar and connective tissue protein synthesis in contracting skeletal muscle

We tested the hypothesis that acute exercise would stimulate synthesis of myofibrillar protein and intramuscular collagen in women and that the phase of the menstrual cycle at which the exercise took place would influence the extent of the change. Fifteen young, healthy female subjects were studied in the follicular (FP, n=8) or the luteal phase (LP, n=7, n=1 out of phase) 24 h after an acute bout of one-legged exercise (60 min of kicking at 67% W(max)), samples being taken from the vastus lateralis in both the exercised and resting legs. Rates of synthesis of myofibrillar and muscle collagen proteins were measured by incorporation of [(13)C]leucine. Myofibrillar protein synthesis (means+/-SD; rest FP: 0.053+/-0.009%/h, LP: 0.055+/-0.013%/h) was increased at 24-h postexercise (FP: 0.131+/-0.018%/h, P<0.05, LP: 0.134+/-0.018%/h, P< 0.05) with no differences between phases. Similarly, muscle collagen synthesis (rest FP: 0.024+/- 0.017%/h, LP: 0.021+/- 0.006%/h) was elevated at 24-h postexercise (FP: 0.073+/- 0.016%/h, P<0.05, LP: 0.072+/- 0.015%/h, P<0.05), but the responses did not differ between menstrual phases. Therefore, there is no effect of menstrual cycle phase, at rest or in response to an acute bout of exercise, on myofibrillar protein synthesis and muscle collagen synthesis in women.     

Effects of resistance training on myosin function studied by the in vitro motility assay in young and older men.

It is generally believed that the maximum shortening velocity (V(o)) of a skeletal muscle fiber type does not vary unless a change in myosin heavy chain (MHC) isoform composition occurs. However, recent findings have shown that V(o) of a given fiber type can change after training, suggesting the hypothesis that the function of myosin can vary without a change in isoform. The present study addressed the latter hypothesis by studying the function of isolated myosin isoforms by the use of the in vitro motility assay (IVMA) technique. Four young (age 23-29 yr, YO) and four elderly men (age 68-82 yr, EL) underwent a 12-wk progressive resistance training program of the knee extensor muscles and to one pre- and one posttraining biopsy of the vastus lateralis muscle. The significant increase in one-repetition maximum posttraining in both YO and EL indicated that training was effective. After training, MHC isoform composition showed a shift from MHC(2X) toward MHC(2A) in YO and no shift in EL. The velocity of sliding (V(f)) of actin filaments on pure myosin isoforms extracted from single fibers was studied in IVMA. One hundred sixty IVMA samples were prepared from 480 single fibers, and at least 50 filaments were analyzed in each experiment. Whereas no training-induced change was observed in V(f) of myosin isoform 1 either in YO or in EL, a significant increase in V(f) of myosin isoform 2A after training was observed in both YO (18%) and EL (19%). The results indicate that resistance training can change the velocity of the myosin molecule.     

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.     

Effects of exercise on plasma myosin heavy chain fragments and MRI of skeletal muscle.

The effects of a single series of high-force eccentric contractions involving the quadriceps muscle group (single leg) on plasma concentrations of muscle proteins were examined as a function of time, in the context of measurements of torque production and magnetic resonance imaging (MRI) of the involved muscle groups. Plasma concentrations of slow-twitch skeletal (cardiac beta-type) myosin heavy chain (MHC) fragments, myoglobin, creatine kinase (CK), and cardiac troponin T were measured in blood samples of six healthy male volunteers before and 2 h after 70 eccentric contractions of the quadriceps femoris muscle. Screenings were conducted 1, 2, 3, 6, 9, and 13 days later. To visualize muscle injury, MRI of the loaded and unloaded thighs was performed 3, 6, and 9 days after the eccentric exercise bout. Force generation of the knee extensors was monitored on a dynamometer (Cybex II+) parallel to blood sampling. Exercise resulted in a biphasic myoglobin release profile, delayed CK and MHC peaks. Increased MHC fragment concentrations of slow skeletal muscle myosin occurred in late samples of all participants, which indicated a degradation of slow skeletal muscle myosin. Because cardiac troponin T was within the normal range in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for an injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Muscle action revealed delayed reversible increases in MRI signal intensities on T2-weighted images of the loaded vastus intermedius and deep parts of the vastus lateralis. We attributed MRI signal changes due to edema in part to slow skeletal muscle fiber injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contractile and connective tissue protein content of human skeletal muscle: effects of 35 and 90 days of simulated microgravity and exercise countermeasures

We examined the effects of 35 and 90 days of simulated microgravity with or without resistance-exercise (RE) countermeasures on the content of the general skeletal muscle protein fractions (mixed, sarcoplasmic, and myofibrillar) and specific proteins that are critical for muscle function (myosin, actin, and collagen). Subjects from two studies, using either unilateral lower limb suspension (ULLS) or bed rest (BR), comprised four separate groups: 35 days ULLS (n =11), 35 days ULLS+RE (n = 10), 90 days BR (n = 9), and 90 days BR+RE (n = 8). RE consisted of four sets of seven maximal concentric and eccentric repetitions of the quadriceps femoris muscles that were performed 2 or 3 times per week. Pre- and post-simulated weightlessness muscle biopsies were analyzed from the vastus lateralis of all groups and the soleus of the 35-day ULLS and 90-day BR groups. The general protein fractions and the specific proteins myosin, actin, and collagen of the vastus lateralis were unchanged (P > 0.05) in both control and countermeasures groups over 35 and 90 days, despite large changes in quadriceps femoris muscle volume (35 days ULLS: -9%, 35 days ULLS+RE: +8%; and 90 days BR: -18%, 90 days BR+RE: -1%). The soleus demonstrated a decrease in mixed (35 days ULLS: -12%, P = 0.0001; 90 days BR: -12%, P = 0.004) and myofibrillar (35 days ULLS: -12%, P = 0.009; 90 days BR: -8%, P = 0.04) protein, along with large changes in triceps surae muscle volume (35 days ULLS: -11%; 90 days BR: -29%). Despite the loss of quadriceps femoris muscle volume or preservation with RE countermeasures during simulated microgravity, the quadriceps femoris muscles are able to maintain the concentrations of the general protein pools and the main contractile and connective tissue elements. Soleus muscle protein composition appears to be disproportionately altered during long-duration simulated weightlessness.     

Neuromuscular electrical stimulation training induces atypical adaptations of the human skeletal muscle phenotype: a functional and proteomic analysis

The aim of the present study was to define the chronic effects of neuromuscular electrical stimulation (NMES) on the neuromuscular properties of human skeletal muscle. Eight young healthy male subjects were subjected to 25 sessions of isometric NMES of the quadriceps muscle over an 8-wk period. Needle biopsies were taken from the vastus lateralis muscle before and after training. The training status, myosin heavy chain (MHC) isoform distribution, and global protein pattern, as assessed by proteomic analysis, widely varied among subjects at baseline and prompted the identification of two subgroups: an "active" (ACT) group, which performed regular exercise and had a slower MHC profile, and a sedentary (SED) group, which did not perform any exercise and had a faster MHC profile. Maximum voluntary force and neural activation significantly increased after NMES in both groups (+～30% and +～10%, respectively). Both type 1 and 2 fibers showed significant muscle hypertrophy. After NMES, both groups showed a significant shift from MHC-2X toward MHC-2A and MHC-1, i.e., a fast-to-slow transition. Proteomic maps showing ～500 spots were obtained before and after training in both groups. Differentially expressed proteins were identified and grouped into functional categories. The most relevant changes regarded 1) myofibrillar proteins, whose changes were consistent with a fast-to-slow phenotype shift and with a strengthening of the cytoskeleton; 2) energy production systems, whose changes indicated a glycolytic-to-oxidative shift in the metabolic profile; and 3) antioxidant defense systems, whose changes indicated an enhancement of intracellular defenses against reactive oxygen species. The adaptations in the protein pattern of the ACT and SED groups were different but were, in both groups, typical of both resistance (i.e., strength gains and hypertrophy) and endurance (i.e., a fast-to-slow shift in MHC and metabolic profile) training. These training-induced adaptations can be ascribed to the peculiar motor unit recruitment pattern associated with NMES.     

Muscle-specific atrophy of the quadriceps femoris with aging.

We examined the size of the four muscles of the quadriceps femoris in young and old men and women to assess whether the vastus lateralis is an appropriate surrogate for the quadriceps femoris in human studies of aging skeletal muscle. Ten young (24 +/- 2 yr) and ten old (79 +/- 7 yr) sedentary individuals underwent magnetic resonance imaging of the quadriceps femoris after 60 min of supine rest. Volume (cm3) and average cross-sectional area (CSA, cm2) of the rectus femoris (RF), vastus lateralis (VL), vastus intermedius (VI), vastus medialis (VM), and the total quadriceps femoris were decreased (P < 0.05) in older compared with younger women and men. However, percentage of the total quadriceps femoris taken up by each muscle was similar (P > 0.05) between young and old (RF: 10 +/- 0.3 vs. 11 +/- 0.4; VL: 33 +/- 1 vs. 33 +/- 1; VI: 31 +/- 1 vs. 31 +/- 0.4; VM: 26 +/- 1 vs. 25 +/- 1%). These results suggest that each of the four muscles of the quadriceps femoris atrophy similarly in aging men and women. Our data support the use of vastus lateralis tissue to represent the quadriceps femoris muscle in aging research.     

Temporal response of desmin and dystrophin proteins to progressive resistance exercise in human skeletal muscle.

We have investigated the adaptations of the cytoskeletal proteins desmin and dystrophin in relationship to known muscular adaptations of resistance exercise. We measured desmin, dystrophin, and actin protein contents, myosin heavy chain (MHC) isoform distribution, muscle strength, and muscle cross-sectional area (CSA) during 8 wk of progressive resistance training or after a single bout of unaccustomed resistance exercise. Muscle biopsies were taken from the vastus lateralis of 12 untrained men. For the single-bout group (n=6) biopsies were taken 1 wk before the single bout of exercise (week 0) and 1, 2, 4, and 8 wk after this single bout of exercise. For the training group (n=6), biopsies were taken 1 wk before the beginning of the program (week 0) and at weeks 1, 2, 4, and 8 of the progressive resistance training program. Desmin, dystrophin, and actin protein levels were determined with immunoblotting, and MHC isoform distribution was determined using SDS-PAGE at each time point for each group. In the training group, desmin was significantly increased compared with week 0 beginning at week 4 (182% of week 0; P<0.0001) and remained elevated through week 8 (172% of week 0; P<0.0001). Desmin did not change at any time point for the single-bout group. Actin and dystrophin protein contents were not changed in either group at any time point. The percentage of MHC type IIa increased and MHC type IIx decreased at week 8 in the training group with no changes occurring in the single-bout group. Strength was significantly increased by week 2 (knee extension) and week 4 (leg press), and it further increased at week 8 for both these exercises in the training group only. Muscle CSA was significantly increased at week 4 for type II fibers in the training group only (5,719+/-382 and 6,582+/-640 microm2, weeks 0 and 4, respectively; P<0.05). Finally, a significant negative correlation was observed between the desmin-to-actin ratio and the percentage of MHC IIx (R=-0.31; P<0.05, all time points from both groups). These data demonstrate a time course for muscular adaptation to resistance training in which desmin increases shortly after strength gains and in conjunction with hypertrophy, but before changes in MHC isoforms, whereas dystrophin remains unchanged.     

Age and aerobic exercise training effects on whole body and muscle protein metabolism

Aging in humans is associated with loss of lean body mass, but the causes are incompletely defined. Lean tissue mass and function depend on continuous rebuilding of proteins. We tested the hypotheses that whole body and mixed muscle protein metabolism declines with age in men and women and that aerobic exercise training would partly reverse this decline. Seventy-eight healthy, previously untrained men and women aged 19-87 yr were studied before and after 4 mo of bicycle training (up to 45 min at 80% peak heart rate, 3-4 days/wk) or control (flexibility) activity. At the whole body level, protein breakdown (measured as [13C]leucine and [15N]phenylalanine flux), Leu oxidation, and protein synthesis (nonoxidative Leu disposal) declined with age at a rate of 4-5% per decade (P < 0.001). Fat-free mass was closely correlated with protein turnover and declined 3% per decade (P < 0.001), but even after covariate adjustment for fat-free mass, the decline in protein turnover with age remained significant. There were no differences between men and women after adjustment for fat-free mass. Mixed muscle protein synthesis also declined with age 3.5% per decade (P < 0.05). Exercise training improved aerobic capacity 9% overall (P < 0.01), and mixed muscle protein synthesis increased 22% (P < 0.05), with no effect of age on the training response for either variable. Fat-free mass, whole body protein turnover, and resting metabolic rate were unchanged by training. We conclude that rates of whole body and muscle protein metabolism decline with age in men and women, thus indicating that there is a progressive decline in the body's remodeling processes with aging. This study also demonstrates that aerobic exercise can enhance muscle protein synthesis irrespective of age.     

Functional impact of high protein intake on healthy elderly people

Decline in muscle mass, protein synthesis, and mitochondrial function occurs with age, and amino acids are reported to enhance both muscle protein synthesis and mitochondrial function. It is unclear whether increasing dietary protein intake corrects postabsorptive muscle changes in aging. We determined whether a 10-day diet of high [HP; 3.0 g protein x kg fat-free mass (FFM)(-1) x day(-1)] vs. usual protein intake (UP; 1.5 g protein x kg FFM(-1) x day(-1)) favorably affects mitochondrial function, protein metabolism, and nitrogen balance or adversely affects insulin sensitivity and glomerular filtration rate (GFR) in 10 healthy younger (24+/-1 yr) and 9 older (70+/-2 yr) participants in a randomized crossover study. Net daily nitrogen balance increased equally in young and older participants, but postabsorptive catabolic state also increased, as indicated by higher whole body protein turnover and leucine oxidation with no change in protein synthesis. Maximal muscle mitochondrial ATP production rate was lower in older people, with no change occurring in diet. GFR was lower in older people, and response to HP was significantly different between the two groups, with a significant increase occurring only in younger people, thus widening the differences in GFR between the young and older participants. In conclusion, a short-term high-protein diet increased net daily nitrogen balance but increased the postabsorptive use of protein as a fuel. HP did not enhance protein synthesis or muscle mitochondrial function in either young or older participants. Additionally, widening differences in GFR between young and older patients is a potential cause of concern in using HP diet in older people.     

Fiber type composition of the vastus lateralis muscle of young men and women.

This study presents data collected over the past 10 years on the muscle fiber type composition of the vastus lateralis muscle of young men and women. Biopsies were taken from the vastus lateralis muscle of 55 women (21.2+/-2.2 yr) and 95 men (21.5+/-2.4 yr) who had volunteered to participate in various research projects. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were classified using mATPase histochemistry, and cross-sectional area was measured for the major fiber types (I, IIA, and IIB). Myosin heavy chain (MHC) content was determined electrophoretically on all of the samples from the men and on 26 samples from the women. With the exception of fiber Type IC, no significant differences were found between men and women for muscle fiber type distribution. The vastus lateralis muscle of both the men and women contained approximately 41% I, 1% IC, 1% IIC, 31% IIA, 6% IIAB, and 20% IIB. However, the cross-sectional area of all three major fiber types was larger for the men compared to the women. In addition, the Type IIA fibers were the largest for the men, whereas the Type I fibers tended to be the largest for the women. Therefore, gender differences were found with regard to the area occupied by each specific fiber type: IIA>I>IIB for the men and I>IIA>IIB for the women. These data establish normative values for the mATPase-based fiber type distribution and sizes in untrained young men and women.     

Functional properties of human muscle fibers after short-term resistance exercise training

The aim of this study was to assess the relationships between human muscle fiber hypertrophy, protein isoform content, and maximal Ca(2+)-activated contractile function following a short-term period of resistance exercise training. Six male subjects (age 27 +/- 2 yr) participated in a 12-wk progressive resistance exercise training program that increased voluntary lower limb extension strength by >60%. Single chemically skinned fibers were prepared from pre- and posttraining vastus lateralis muscle biopsies. Training increased the cross-sectional area (CSA) and peak Ca(2+)-activated force (P(o)) of fibers containing type I, IIa, or IIa/IIx myosin heavy chain by 30-40% without affecting fiber-specific force (P(o)/CSA) or unloaded shortening velocity (V(o)). Absolute fiber peak power rose as a result of the increase in P(o), whereas power normalized to fiber volume was unchanged. At the level of the cross bridge, the effects of short-term resistance training were quantitative (fiber hypertrophy and proportional increases in fiber P(o) and absolute power) rather than qualitative (no change in P(o)/CSA, V(o), or power/fiber volume).     

Essential amino acids and muscle protein recovery from resistance exercise

This study tests the hypothesis that a dose of 6 g of orally administered essential amino acids (EAAs) stimulates net muscle protein balance in healthy volunteers when consumed 1 and 2 h after resistance exercise. Subjects received a primed constant infusion of L-[(2)H(5)]phenylalanine and L-[1-(13)C]leucine. Samples from femoral artery and vein and biopsies from vastus lateralis were obtained. Arterial EAA concentrations increased severalfold after drinks. Net muscle protein balance (NB) increased proportionally more than arterial AA concentrations in response to drinks, and it returned rapidly to basal values when AA concentrations decreased. Area under the curve for net phenylalanine uptake above basal value was similar for the first hour after each drink (67 +/- 17 vs. 77 +/- 20 mg/leg, respectively). Because the NB response was double the response to two doses of a mixture of 3 g of EAA + 3 g of nonessential AA (NEAA) (14), we conclude that NEAA are not necessary for stimulation of NB and that there is a dose-dependent effect of EAA ingestion on muscle protein synthesis.