Force depression and relaxation kinetics after active shortening and deactivation in mouse soleus muscle.

After active shortening, isometric force production capacity of muscle is reduced (force depression, FD). The mechanism is incompletely understood but increasing cross-bridge detachment and/or decreasing attachment rate might be involved. Therefore we aimed to investigate the relation between work delivered during shortening (W), and change in half-relaxation time (Δ0.5RT) and change in the slow phase of muscle relaxation (Δkslow), considered as a marker for cross-bridge detachment rate, after shortening and after a short (0.7s) interruption of activation (deactivation). We hypothesized that shortening induces an accelerated relaxation related to W which is, similar to FD, largely abolished by a short deactivation. In 10 incubated supra-maximally stimulated mouse soleus muscles, we varied the amount of FD at L0 by varying shortening amplitude (0.6, 1.2 and 2.4mm). We found that W not only induces FD (R(2)=0.92) but also a dose dependent accelerated relaxation (R(2)=0.88 and R(2)=0.77 for respectively Δkslow and Δ0.5RT). In cyclic movements this is of functional significance, because the loss in force generating capacity might be (partially) compensated by faster relaxation. After a short deactivation, both FD and Δkslow were largely abolished but Δ0.5RT remained largely present. Under the assumption that Δkslow reflects a change in cross-bridge detachment rate, these results support the idea that FD is an intrinsic sarcomeric property originating from a work induced reduction of the number of force generating cross-bridges, however not via decreased attachment but via increased detachment rate.

Alpha-actinin-3 deficiency does not significantly alter oxidative enzyme activity in fast human muscle fibres.

AIM: In Western European populations, about 18% of all individuals have a complete deficiency of the alpha-actinin-3 protein owing to homozygosity for a stop codon mutation (R577X) in the ACTN3 gene. Actn3(-/-) knock-out mice show increased activity of multiple enzymes in the aerobic metabolic pathway in fast muscle fibres. Whether this observation is also present in human XX genotype carriers compared to RR carriers has not been studied in a fibre-type-specific approach in humans. The purpose of this study was therefore to compare fibre-type-specific oxidative enzyme activity in humans with a different ACTN3 R577X genotype. METHODS: Vastus lateralis muscle biopsy samples of 17 XX and 16 RR subjects were used to measure markers of oxidative capacity [cytochrome c oxidase (CYTOX) and succinate dehydrogenase (SDH)] in a fibre-type-specific assay using enzyme histochemistry. RESULTS: Cytochrome c oxidase staining showed no significant genotype group differences in type I or type II muscle fibres. Also, we found no significant differences in SDH staining of fast fibres comparing XX and RR carriers. CONCLUSION: In conclusion, the increase in oxidative enzyme activity of fast muscle fibres, as reported in an Actn3(-/-) knock-out mouse, was not observed in our human samples. Known differences in metabolic characteristics of muscle fibres in rodents compared to humans may in part explain this discrepancy in findings.

Creatine supplementation in Huntington's disease: a placebo-controlled pilot trial.

OBJECTIVE: To evaluate the effect of creatine (Cr) supplementation (5 g/day) in Huntington's disease (HD). METHODS: A 1-year double-blind placebo-controlled study was performed in 41 patients with HD (stage I through III). At baseline and after 6 and 12 months, the functional, neuromuscular, and cognitive status of the patients was assessed by a test battery that consisted of 1) the Unified Huntington's Disease Rating Scale (UHDRS), 2) an exercise test on an isokinetic dynamometer to assess strength of the elbow flexor muscles, 3) a maximal exercise test on a bicycle ergometer to evaluate cardiorespiratory fitness, and 4) a test to assess bimanual coordination ability. Following the baseline measurements, the subjects were assigned to either a creatine (n = 26) or a placebo group (n = 15). RESULTS: Scores on the functional checklist of the UHDRS (p < 0.05), maximal static torque (p < 0.05), and peak oxygen uptake (p < 0.05) decreased from the start to the end of the study, independent of the treatment received. Cognitive functioning, bimanual coordination ability, and general motor function (total motor scale, UHDRS) did not change from baseline to 1 year in either group. CONCLUSION: One year of Cr intake, at a rate that can improve muscle functional capacity in healthy subjects and patients with neuromuscular disease (5 g/day), did not improve functional, neuromuscular, and cognitive status in patients with stage I to III HD.

Effects of oral creatine-pyruvate supplementation in cycling performance.

A double-blind study was performed to evaluate the effects of oral creatine-pyruvate administration on exercise performance in well-trained cyclists. Endurance and intermittent sprint performance were evaluated before (pretest) and after (posttest) one week of creatine-pyruvate intake (Cr(pyr), 2 x 3.5 g x d-1, n = 7) or placebo (PL, n = 7). Subjects first performed a 1-hour time trial during which the workload could be adjusted at 5-min intervals. Immediately they did five 10-sec sprints interspersed by 2-min rest intervals. Tests were performed on an individual race bicycle that was mounted on an ergometer. Steady-state power production on average was about 235-245 W, which corresponded to blood lactate concentrations of 4-5 mmol x l -1 and heart rate in the range of 160-170 beats x min -1. Power outputs as well as blood lactate levels and heart rates were similar between Cr(pyr) and PL at all times. Total work performed during the 1-h trial was 872 +/- 44 KJ in PL versus 891 +/- 51 KJ in CR pyr. During the intermittent sprint test power peaked at about 800-1000 watt within 2-3 sec, decreasing by 15-20 % towards the end of each sprint. Peak and mean power outputs were similar between groups at all times. Peak lactate concentrations after the final sprint were approximately 11 mmol x l -1 in both groups during both the pretest and the posttest. It is concluded that one week of creatine-pyruvate supplementation at a rate of 7 g x d -1 does not beneficially impact on either endurance capacity or intermittent sprint performance in cyclists.

Effect of immobilization and retraining on torque-velocity relationship of human knee flexor and extensor muscles.

The effect of 2 weeks immobilization of the uninjured right knee and 10 weeks of retraining on muscle torque-velocity characteristics was investigated in nine young subjects. Left and right knee extension and flexion maximal voluntary isometric torque (Tmax) and dynamic torque at 60 degrees s(-1) (T60) and 180 degrees x s(-1) (T180) were measured before (PRE) and after immobilization (POST) and after 3 (R3) and 10 (R10) weeks of dynamic retraining. The torque-velocity relationship was quantified by expressing T60 and T180 relative to Tmax (NT60 and NT180, respectively). For the right extensor muscles, percutaneous biopsy samples were obtained from the vastus lateralis muscle and fibre type distribution was measured. POST extension and flexion torque (mean of Tmax, T60 and T180) decreased by 27% and 11%, respectively. During the course of the experiment, the changes in NT60 and NT180 were similar. POST extensor muscle NTV (mean of NT60 and NT180) was decreased significantly (12%, P<0.05), but no significant change was found for flexor muscle NTV (+ 3%). At R3 Tmax, dynamic torque and NTV were restored to normal. Unlike isometric torque, NTV did not change from R3 to R10. No changes in fibre type distribution were found. The adaptation of muscle length is suggested as the mechanism to explain the change in NTV.

Opposite actions of caffeine and creatine on muscle relaxation time in humans.

The effect of creatine and caffeine supplementation on muscle torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (T(max)), contraction time (CT) from 0.25 to 0.75 of T(max), and relaxation time (RT) from 0.75 to 0.25 of T(max) were measured during an exercise test consisting of 30 intermittent contractions of musculus quadriceps (2 s stimulation, 2 s rest) that were induced by electrical stimulation. According to a double-blind randomized crossover design, subjects (n = 10) performed the exercise test before (pretest) and after (posttest) creatine supplementation (Cr, 4 x 5 g/day, 4 days), short-term caffeine intake (Caf, 5 mg x kg(-1) x day(-1), 3 days), creatine supplementation + short-term caffeine intake (Cr+Caf), acute caffeine intake (ACaf, 5 mg/kg) or placebo. Compared with placebo, Cr shortened RT by approximately 5% (P < 0.05). Conversely, Caf increased RT (+ approximately 10%, P < 0.05), in particular as RT increased because of fatigue. RT was not significantly changed by either Cr+Caf or ACaf. T(max) and CT were similar during all experimental conditions. Initial T(max) was approximately 20% of voluntary maximal isometric contraction force, which was not different between treatments. It is concluded that Caf intake (3 days) prolongs muscle RT and by this action overrides the shortening of RT due to creatine supplementation.

Oral creatine supplementation facilitates the rehabilitation of disuse atrophy and alters the expression of muscle myogenic factors in humans.

1. We investigated the effect of oral creatine supplementation during leg immobilization and rehabilitation on muscle volume and function, and on myogenic transcription factor expression in human subjects. 2. A double-blind trial was performed in young healthy volunteers (n = 22). A cast was used to immobilize the right leg for 2 weeks. Thereafter the subjects participated in a knee-extension rehabilitation programme (3 sessions x week(-1), 10 weeks). Half of the subjects received creatine monohydrate (CR; from 20 g down to 5 g daily), whilst the others ingested placebo (P; maltodextrin). 3. Before and after immobilization, and after 3 and 10 weeks of rehabilitation training, the cross-sectional area (CSA) of the quadriceps muscle was assessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee-extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters. 4. Immobilization decreased quadriceps muscle CSA (approximately 10 %) and Wmax (approximately 25 %) by the same magnitude in both groups. During rehabilitation, CSA and Wmax recovered at a faster rate in CR than in P (P < 0.05 for both parameters). Immobilization changed myogenic factor protein expression in neither P nor CR. However, after rehabilitation myogenin protein expression was increased in P but not in CR (P < 0.05), whilst MRF4 protein expression was increased in CR but not in P (P < 0.05). In addition, the change in MRF4 expression was correlated with the change in mean muscle fibre diameter (r = 0.73, P < 0.05). 5. It is concluded that oral creatine supplementation stimulates muscle hypertrophy during rehabilitative strength training. This effect may be mediated by a creatine-induced change in MRF4 and myogenin expression.

No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis.

A double-blind randomized study was performed to evaluate the effect of oral ribose supplementation on repeated maximal exercise and ATP recovery after intermittent maximal muscle contractions. Muscle power output was measured during dynamic knee extensions with the right leg on an isokinetic dynamometer before (pretest) and after (posttest) a 6-day training period in conjunction with ribose (R, 4 doses/day at 4 g/dose, n = 10) or placebo (P, n = 9) intake. The exercise protocol consisted of two bouts (A and B) of maximal contractions, separated by 15 s of rest. Bouts A and B consisted of 15 series of 12 contractions each, separated by a 60-min rest period. During the training period, the subjects performed the same exercise protocol twice per day, with 3-5 h of rest between exercise sessions. Blood samples were collected before and after bouts A and B and 24 h after bout B. Knee-extension power outputs were approximately 10% higher in the posttest than in the pretest but were similar between P and R for all contraction series. The exercise increased blood lactate and plasma ammonia concentrations (P < 0.05), with no significant differences between P and R at any time. After a 6-wk washout period, in a subgroup of subjects (n = 8), needle-biopsy samples were taken from the vastus lateralis before, immediately after, and 24 h after an exercise bout similar to the pretest. ATP and total adenine nucleotide content were decreased by approximately 25 and 20% immediately after and 24 h after exercise in P and R. Oral ribose supplementation with 4-g doses four times a day does not beneficially impact on postexercise muscle ATP recovery and maximal intermittent exercise performance.

Predictive power of individual genetic and environmental factor scores.

This study explores the use of an individual's genetic (IGFS) and environmental factor score (IEFS), constructed using genetic model fitting of a multivariate strength phenotype. Maximal isometric and dynamic strength measures, one maximal repetition load (1RM) and muscle cross-sectional area (MCSA) were measured in 25 monozygotic and 16 dizygotic twin pairs. The use of IGFS and IEFS in predicting the sensitivity to environmental stress was evaluated by the association of the scores with strength training gains after a 10-week high resistance strength training programme. Results show a high contribution of genetic factors to the covariation between maximal strength and muscle cross-sectional area (84-97%) at pre-training evaluation. Individual factor scores explained the largest part of the variation in IRM and other strength measures at pre-training and post-training evaluation respectively. Genes that are switched on due to training stress (gene-environment interaction) could explain the decrease in explained variation over time. A negative correlation was found between IGFS and strength training gains (-0.24 to -0.51, P < 0.05); individuals with a high IGFS tend to gain less strength than individuals with low IGFS. Individual environmental factor scores have lower differential power. The predictive value of the IGFS has potential utility in identifying an individual's susceptibility to environmental stress in a variety of multifactorial characteristics, eg diseases and impairments, and for selection of sib pairs for QTL analyses.

Shortening of muscle relaxation time after creatine loading.

The effect of creatine (Cr) supplementation on muscle isometric torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmax were measured during 12 maximal isometric 3-s elbow flexions interspersed by 10-s rest intervals. Between the pretest and the posttest, subjects ingested Cr monohydrate (4 x 5 g/day; n = 8) or placebo (n = 8) for 5 days. Pretest Tmax, CT, and RT were similar in Cr and placebo groups. Also in the posttest, Tmax and CT were similar between groups. However, posttest RT was decreased consistently by approximately 20% (P < 0.05) in the Cr group from the first to the last of the 12 contractions. In addition, the mean decrease in RT after Cr loading was positively correlated with pretest RT (r = 0.82). It is concluded that Cr loading facilitates the rate of muscle relaxation during brief isometric muscle contractions without affecting torque production.

Phosphocreatine resynthesis is not affected by creatine loading.

PURPOSE: Oral creatine supplementation has been shown to improve power output during high intensity intermittent muscle contractions. Facilitated muscle phosphocreatine (PCr) resynthesis, by virtue of elevated intracellular PCr concentration, might contribute to this ergogenic action. Therefore, the effect of creatine loading (C: 25 g X d(-1) for 5 d) on muscle PCr breakdown and resynthesis and muscle performance during high intensity intermittent muscle contractions was investigated. METHODS: A double-blind randomized cross-over study was performed in young healthy male volunteers (N = 9). 31P-NMR spectroscopy of the m. gastrocnemius and isokinetic dynamometry of knee-extension torque were performed before and after 2 and 5 d of either placebo (P) or C administration. RESULTS: Compared with P, 2 and 5 d of C increased (P < 0.05) resting muscle PCr concentration by 11% and 16%, respectively. Furthermore, torque production during maximal intermittent knee extensions, including the first bout of contractions, was increased (P < 0.05) by 5-13% by either 2 or 5 d of C. However, compared with P, the rate of PCr breakdown and resynthesis during intermittent isometric contractions of the calf was not significantly affected by C. CONCLUSION: Creatine loading raises muscle PCr concentration and improves performance during rapid and dynamic intermittent muscle contractions. Creatine loading does not facilitate muscle PCr resynthesis during intermittent isometric muscle contractions.

Inheritance of static and dynamic arm strength and some of its determinants.

Maximal static, eccentric and concentric torques and arm components estimated by anthropometry and measured by computed tomography were evaluated in 25 male monozygotic twins and 16 dizygotic twins (22.4 +/- 3.7 years). The importance of genetic and environmental factors in the observed variation in these measurements was estimated by genetic model-fitting techniques. In this sample of young adult male twins, genetic factors were significant in most of the strength measurements, arm muscle components and muscle activation variables. The contribution of genetic factors in strength measures depended on the angle, contraction type and to some extent on contraction velocity. For isometric strength, angle-specificity in genetic and environmental variation could be attributed to the degree of variability in muscle activation and performance discomfort at each specific angle, with the highest unique environmental impact at extreme angles. The high genetic contribution at 170 degrees, but not at 50 degrees, possibly expressed different contributions of genetic factors in the muscle-length factor and moment arm in torques at both angles. The importance of genetic factors in eccentric arm flexor strength (62-82%) was larger than for concentric flexion (29-65%), as the pattern of genetic determination followed the torque-velocity curve. Genetic variations in contractile and elastic components, contributing differently to eccentric and concentric torques, together with velocity-dependent actin-myosin binding factors, could account for the observed differences. The broad heritability was very high for all anthropometric and arm cross-sectional area measurements (> 85%) and common environmental factors were only significant for anthropometrically estimated mid-arm muscle tissue are (48%). Heritability estimates of different arm muscularity measurements were comparable.

Strength training: importance of genetic factors.

PURPOSE: This study focuses on the quantification of genetic and environmental factors in arm strength after high-resistance strength training. METHODS: Male monozygotic (MZ, N = 25) and dizygotic (DZ, N = 16) twins (22.4 +/- 3.7 yr) participated in a 10-wk resistance training program for the elbow flexors. The evidence for genotype*training interaction, or association of interindividual differences in training effects with the genotype, was tested by a two-way ANOVA in the MZ twins and using a bivariate model-fitting approach on pre- and post-training phenotypes in MZ and DZ twins. One repetition maximum (1RM), isometric strength, and concentric and eccentric moments in 110 degree arm flexion at velocities of 30 degrees x s(-1), 60 degrees x s(-1), and 12 degrees x s(-1) were evaluated as well as arm muscle cross-sectional area (MCSA). RESULTS: Results indicated significant positive training effects for all measures except for maximal eccentric moments. Evidence for genotype*training interaction was found for 1RM and isometric strength, with MZ intra-pair correlations of 0.46 and 0.30, respectively. Bivariate model-fitting indicated that about 20% of the variation in post-training 1RM, isometric strength, and concentric moment at 120 degrees x s(-1) was explained by training-specific genetic factors that were independent from genetic factors that explained variation in the pretraining phenotype (30-77%). CONCLUSIONS: Genetic correlations between measures of pre- and post-training strength were indicative for high pleiotropic gene action and minor activation of training-specific genes during training.

Multivariate genetic analysis of maximal isometric muscle force at different elbow angles.

The maximal isometric moment at five different elbow joint angles was measured in 25 monozygotic and 16 dizygotic male adult twin pairs (22.4 +/- 3.7 yr). Genetic model fitting was used to quantify the genetic and environmental contributions to individual differences in isometric strength. Additive genetic factors explained 66-78% of the variance in maximal torque at 170-140-110 and 80 degrees flexion (extension = 180 degrees). At 50 degrees flexion, common and subject-specific environmental factors contributed equally to the variation. The contribution of unique environmental factors concurs with the level of variability in muscle activation and (dis)-comfort of torque production in the specific angle. The relative contribution of lever arm and force-length relationship in torque varies according to the angle. Because these factors might be genetic, this variability is reflected in the genetic contribution at the extreme angles of 170 and 50 degrees. Multivariate analyses suggested a general set of genes that control muscle area and isometric strength, together with a more specific strength factor. Genetic correlations were high (0.82-0.99). Genes responsible for arm-segment lengths did not contribute to muscle area nor to isometric strength.

Long-term creatine intake is beneficial to muscle performance during resistance training.

The effects of oral creatine supplementation on muscle phosphocreatine (PCr) concentration, muscle strength, and body composition were investigated in young female volunteers (n = 19) during 10 wk of resistance training (3 h/wk). Compared with placebo, 4 days of high-dose creatine intake (20 g/day) increased (P < 0.05) muscle PCr concentration by 6%. Thereafter, this increase was maintained during 10 wk of training associated with low-dose creatine intake (5 g/day). Compared with placebo, maximal strength of the muscle groups trained, maximal intermittent exercise capacity of the arm flexors, and fat-free mass were increased 20-25, 10-25, and 60% more (P < 0. 05), respectively, during creatine supplementation. Muscle PCr and strength, intermittent exercise capacity, and fat-free mass subsequently remained at a higher level in the creatine group than in the placebo group during 10 wk of detraining while low-dose creatine was continued. Finally, on cessation of creatine intake, muscle PCr in the creatine group returned to normal within 4 wk. It is concluded that long-term creatine supplementation enhances the progress of muscle strength during resistance training in sedentary females.

Caffeine counteracts the ergogenic action of muscle creatine loading.

This study aimed to compare the effects of oral creatine (Cr) supplementation with creatine supplementation in combination with caffeine (Cr+C) on muscle phosphocreatine (PCr) level and performance in healthy male volunteers (n = 9). Before and after 6 days of placebo, Cr (0.5 g x kg-1 x day-1), or Cr (0.5 g x kg-1 x day-1) + C (5 mg x kg-1 x day-1) supplementation, 31P-nuclear magnetic resonance spectroscopy of the gastrocnemius muscle and a maximal intermittent exercise fatigue test of the knee extensors on an isokinetic dynamometer were performed. The exercise consisted of three consecutive maximal isometric contractions and three interval series of 90, 80, and 50 maximal voluntary contractions performed with a rest interval of 2 min between the series. Muscle ATP concentration remained constant over the three experimental conditions. Cr and Cr+C increased (P < 0.05) muscle PCr concentration by 4-6%. Dynamic torque production, however, was increased by 10-23% (P < 0.05) by Cr but was not changed by Cr+C. Torque improvement during Cr was most prominent immediately after the 2-min rest between the exercise bouts. The data show that Cr supplementation elevates muscle PCr concentration and markedly improves performance during intense intermittent exercise. This ergogenic effect, however, is completely eliminated by caffeine intake.

Influence of high-resistance and high-velocity training on sprint performance.

The purpose of this study is to analyze the effect of high-resistance (HR) and high-velocity (HV) training on the different phases of 100-m sprint performance. Two training groups (HR and HV) were compared with two control groups (RUN and PAS). The HR (N = 22) and HV group (N = 21) trained 3 d.wk-1 for 9 wk: two strength training sessions (HR or HV) and one running session. There was a run control group (RUN, N = 12) that also participated in the running sessions (1 d.wk-1) and a passive control group (PAS, N = 11). Running speed over a 100-m sprint was recorded every 2 m. By means of a principal component analysis on all speed variables, three phases were distinguished: initial acceleration (0-10 m), building-up running speed to a maximum (10-36 m), and maintaining maximum speed in the second part of the run (36-100 m). HV training resulted in improved initial acceleration (P < 0.05 compared with RUN, PAS, and HR), a higher maximum speed (P < 0.05 compared with PAS), and a decreased speed endurance (P < 0.05 compared to RUN and PAS). The HV group improved significantly in total 100 m time (P < 0.05 compared with the RUN and PAS groups). The HR program resulted in an improved initial acceleration phase (P < 0.05 compared with PAS).

Elbow torques and EMG patterns of flexor muscles during different isometric tasks.

This paper examines the torque responses and EMG activity levels in four muscles acting at the elbow joint during different combinations of one- and two- degree of freedom isometric torque production (single and dual tasks, respectively). Flexor and supinator/pronator torques and surface EMG signals from m. biceps brachii, m. brachialis, m. brachioradialis and m. triceps brachii were measured in 16 male subjects while they performed maximal effort isometric contractions of pure flexion, pure supination, pure pronation, combined flexion and supination and combined flexion and pronation. In the single tasks, the torque responses were consistent with task requirements, but the dual task results were surprising in that flexor torque levels were reduced as compared to pure flexion, while supinator/pronator torque levels were as high or higher than in pure supination or pronation. Muscle activity levels varied with task, and could not always explain the differences observed in torque responses. These data are discussed within the framework of subpopulations of task-specific motor units within each muscle. The implications of such task-specific muscle units are related to musculoskeletal modelling and previous EMG - torque relationships found at the elbow.