Physiologic Determinants of Near-Infrared Spectroscopy-Derived Cerebral and Tissue Oxygen Saturation Measurements in Critically Ill Patients.

OBJECTIVES: Near-infrared spectroscopy (NIRS) is a potentially valuable modality to monitor the adequacy of oxygen delivery to the brain and other tissues in critically ill patients, but little is known about the physiologic determinants of NIRS-derived tissue oxygen saturations. The purpose of this study was to assess the contribution of routinely measured physiologic parameters to tissue oxygen saturation measured by NIRS. DESIGN: An observational sub-study of patients enrolled in the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomized feasibility trial. SETTING: Two ICUs in the United Kingdom. PATIENTS: Patients were recruited for the RADAR-2 study, which compared a conservative approach to fluid therapy and deresuscitation with usual care. Those included in this sub-study underwent continuous NIRS monitoring of cerebral oxygen saturations (SctO2) and quadriceps muscle tissue saturations (SmtO2). INTERVENTION: Synchronized and continuous mean arterial pressure (MAP), heart rate (HR), and pulse oximetry (oxygen saturation, Spo2) measurements were recorded alongside NIRS data. Arterial Paco2, Pao2, and hemoglobin concentration were recorded 12 hourly. Linear mixed effect models were used to investigate the association between these physiologic variables and cerebral and muscle tissue oxygen saturations. MEASUREMENTS AND MAIN RESULTS: Sixty-six patients were included in the analysis. Linear mixed models demonstrated that Paco2, Spo2, MAP, and HR were weakly associated with SctO2 but only explained 7.1% of the total variation. Spo2 and MAP were associated with SmtO2, but together only explained 0.8% of its total variation. The remaining variability was predominantly accounted for by between-subject differences. CONCLUSIONS: Our findings demonstrated that only a small proportion of variability in NIRS-derived cerebral and tissue oximetry measurements could be explained by routinely measured physiologic variables. We conclude that for NIRS to be a useful monitoring modality in critical care, considerable further research is required to understand physiologic determinants and prognostic significance.

Muscle strength, quantity and quality and muscle fat quantity and their association with oxidative stress in patients with facioscapulohumeral muscular dystrophy: Effect of antioxidant supplementation.

The purpose of this study was to identify causes of quadriceps muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). To this aim, we evaluated quadriceps muscle and fat volumes by magnetic resonance imaging and their relationships with muscle strength and oxidative stress markers in adult patients with FSHD (n = 32) and healthy controls (n = 7), and the effect of antioxidant supplementation in 20 of the 32 patients with FSHD (n = 10 supplementation and n = 10 placebo) (NCT01596803). Compared with healthy controls, the dominant quadriceps strength and quality (muscle strength per unit of muscle volume) were decreased in patients with FSHD. In addition, fat volume was increased, without changes in total muscle volume. Moreover, in patients with FSHD, the lower strength of the non-dominant quadriceps was associated with lower muscle quality compared with the dominant muscle. Antioxidant supplementation significantly changed muscle and fat volumes in the non-dominant quadriceps, and muscle quality in the dominant quadriceps. This was associated with improved muscle strength (both quadriceps) and antioxidant response. These findings suggest that quadriceps muscle strength decline may not be simply explained by atrophy and may be influenced also by the muscle intrinsic characteristics. As FSHD is associated with increased oxidative stress, supplementation might reduce oxidative stress and increase antioxidant defenses, promoting changes in muscle function.

The effects of resistance training on denervated myofibers, senescent cells, and associated protein markers in middle-aged adults.

Denervated myofibers and senescent cells are hallmarks of skeletal muscle aging. However, sparse research has examined how resistance training affects these outcomes. We investigated the effects of unilateral leg extensor resistance training (2 days/week for 8 weeks) on denervated myofibers, senescent cells, and associated protein markers in apparently healthy middle-aged participants (MA, 55 ± 8 years old, 17 females, 9 males). We obtained dual-leg vastus lateralis (VL) muscle cross-sectional area (mCSA), VL biopsies, and strength assessments before and after training. Fiber cross-sectional area (fCSA), satellite cells (Pax7+), denervated myofibers (NCAM+), senescent cells (p16+ or p21+), proteins associated with denervation and senescence, and senescence-associated secretory phenotype (SASP) proteins were analyzed from biopsy specimens. Leg extensor peak torque increased after training (p < .001), while VL mCSA trended upward (interaction p = .082). No significant changes were observed for Type I/II fCSAs, NCAM+ myofibers, or senescent (p16+ or p21+) cells, albeit satellite cells increased after training (p = .037). While >90% satellite cells were not p16+ or p21+, most p16+ and p21+ cells were Pax7+ (>90% on average). Training altered 13 out of 46 proteins related to muscle-nerve communication (all upregulated, p < .05) and 10 out of 19 proteins related to cellular senescence (9 upregulated, p < .05). Only 1 out of 17 SASP protein increased with training (IGFBP-3, p = .031). In conclusion, resistance training upregulates proteins associated with muscle-nerve communication in MA participants but does not alter NCAM+ myofibers. Moreover, while training increased senescence-related proteins, this coincided with an increase in satellite cells but not alterations in senescent cell content or SASP proteins. These latter findings suggest shorter term resistance training is an unlikely inducer of cellular senescence in apparently healthy middle-aged participants. However, similar study designs are needed in older and diseased populations before definitive conclusions can be drawn.

Curcumin regulates autophagy through SIRT3-SOD2-ROS signaling pathway to improve quadriceps femoris muscle atrophy in KOA rat model.

Knee osteoarthritis (KOA) usually leads to quadriceps femoris atrophy, which in turn can further aggravate the progression of KOA. Curcumin (CUR) has anti-inflammatory and antioxidant effects and has been shown to be a protective agent for skeletal muscle. CUR has been shown to have a protective effect on skeletal muscle. However, there are no studies related to whether CUR improves KOA-induced quadriceps femoris muscle atrophy. We established a model of KOA in rats. Rats in the experimental group were fed CUR for 5 weeks. Changes in autophagy levels, reactive oxygen species (ROS) levels, and changes in the expression of the Sirutin3 (SIRT3)-superoxide dismutase 2 (SOD2) pathway were detected in the quadriceps femoris muscle of rats. KOA led to quadriceps femoris muscle atrophy, in which autophagy was induced and ROS levels were increased. CUR increased SIRT3 expression, decreased SOD2 acetylation and ROS levels, inhibited the over-activation of autophagy, thereby alleviating quadriceps femoris muscle atrophy and improving KOA. CUR has a protective effect against quadriceps femoris muscle atrophy, and KOA is alleviated after improvement of quadriceps femoris muscle atrophy, with the possible mechanism being the reduction of ROS-induced autophagy via the SIRT3-SOD2 pathway.

Differential utilisation of subcellular skeletal muscle glycogen pools: a comparative analysis between 1 and 15 min of maximal exercise.

In skeletal muscle, glycogen particles are distributed both within and between myofibrils, as well as just beneath the sarcolemma. Their precise localisation may influence their degradation rate. Here, we investigated how exercise at different intensities and durations (1- and 15-min maximal exercise) with known variations in glycogenolytic rate and contribution from anaerobic metabolism affects utilisation of the distinct pools. Furthermore, we investigated how decreased glycogen availability achieved through lowering carbohydrate and energy intake after glycogen-depleting exercise affect the storage of glycogen particles (size, numerical density, localisation). Twenty participants were divided into two groups performing either a 1-min (n = 10) or a 15-min (n = 10) maximal cycling exercise test. In a randomised, counterbalanced, cross-over design, the exercise tests were performed following short-term consumption of two distinct diets with either high or moderate carbohydrate content (10 vs. 4 g kg-1 body mass (BM) day-1) mediating a difference in total energy consumption (240 vs. 138 g kg-1 BM day-1). Muscle biopsies from m. vastus lateralis were obtained before and after the exercise tests. Intermyofibrillar glycogen was preferentially utilised during the 1-min test, whereas intramyofibrillar glycogen was preferentially utilised during the 15-min test. Lowering carbohydrate and energy intake after glycogen-depleting exercise reduced glycogen availability by decreasing particle size across all pools and diminishing numerical density in the intramyofibrillar and subsarcolemmal pools. In conclusion, distinct subcellular glycogen pools were differentially utilised during 1-min and 15-min maximal cycling exercise. Additionally, lowered carbohydrate and energy consumption after glycogen-depleting exercise altered glycogen storage by reducing particle size and numerical density, depending on subcellular localisation. KEY POINTS: In human skeletal muscle, glycogen particles are localised in distinct subcellular compartments, referred to as intermyofibrillar, intramyofibrillar and subsarcolemmal pools. The intermyofibrillar and subsarcolemmal pools are close to mitochondria, while the intramyofibrillar pool is at a distance from mitochondria. We show that 1 min of maximal exercise is associated with a preferential utilisation of intermyofibrillar glycogen, and, on the other hand, that 15 min of maximal exercise is associated with a preferential utilisation of intramyofibrillar glycogen. Furthermore, we demonstrate that reduced glycogen availability achieved through lowering carbohydrate and energy intake after glycogen-depleting exercise is characterised by a decreased glycogen particle size across all compartments, with the numerical density only diminished in the intramyofibrillar and subsarcolemmal compartments. These results suggest that exercise intensity influences the subcellular pools of glycogen differently and that the dietary content of carbohydrates and energy is linked to the size and subcellular distribution of glycogen particles.

The effect of neuromuscular electrical stimulation on the human skeletal muscle transcriptome.

AIM: The influence on acute skeletal muscle transcriptomics of neuromuscular electrical stimulation (NMES), as compared to established exercises, is poorly understood. We aimed to investigate the effects on global mRNA-expression in the quadriceps muscle early after a single NMES-session, compared to the effects of voluntary knee extension exercise (EX), and to explore the discomfort level. METHODS: Global vastus lateralis muscle gene expression was assessed (RNA-sequencing) in 30 healthy participants, before and 3 h after a 30-min session of NMES and/or EX. The NMES-treatment was applied using textile electrodes integrated in pants and set to 20% of each participant's pre-tested MVC mean (±SD) 200 (±80) Nm. Discomfort was assessed using Visual Analogue Scale (VAS, 0-10). The EX-protocol was performed at 80% of 1-repetition-maximum. RESULTS: NMES at 20% of MVC resulted in VAS below 4 and induced 4448 differentially expressed genes (DEGs) with 80%-overlap of the 2571 DEGs of EX. Genes well-known to be up-regulated following exercise, for example, PPARGC1A, ABRA, VEGFA, and GDNF, were also up-regulated by NMES. Gene set enrichment analysis demonstrated many common pathways after EX and NMES. Also, some pathways were exclusive to either EX, for example, muscle tissue proliferation, or to NMES, for example, neurite outgrowth and connective tissue proliferation. CONCLUSION: A 30-min NMES-session at 20% of MVC with NMES-pants, which can be applied with an acceptable level of discomfort, induces over 4000 DEGs, of which 80%-overlap with DEGs of EX. NMES can induce exercise-like molecular effects, that potentially can lead to health and performance benefits in individuals who are unable to perform resistance exercise.

NASA SPRINT exercise program efficacy for vastus lateralis and soleus skeletal muscle health during 70 days of simulated microgravity.

The efficacy of the NASA SPRINT exercise countermeasures program for quadriceps (vastus lateralis) and triceps surae (soleus) skeletal muscle health was investigated during 70 days of simulated microgravity. Individuals completed 6° head-down-tilt bedrest (BR, n = 9), bedrest with resistance and aerobic exercise (BRE, n = 9), or bedrest with resistance and aerobic exercise and low-dose testosterone (BRE + T, n = 8). All groups were periodically tested for muscle (n = 9 times) and aerobic (n = 4 times) power during bedrest. In BR, surprisingly, the typical bedrest-induced decrements in vastus lateralis myofiber size and power were either blunted (myosin heavy chain, MHC I) or eliminated (MHC IIa), along with no change (P > 0.05) in %MHC distribution and blunted quadriceps atrophy. In BRE, MHC I (vastus lateralis and soleus) and IIa (vastus lateralis) contractile performance was maintained (P > 0.05) or increased (P < 0.05). Vastus lateralis hybrid fiber percentage was reduced (P < 0.05) and energy metabolism enzymes and capillarization were generally maintained (P > 0.05), while not all of these positive responses were observed in the soleus. Exercise offsets 100% of quadriceps and approximately two-thirds of soleus whole muscle mass loss. Testosterone (BRE + T) did not provide any benefit over exercise alone for either muscle and for some myocellular parameters appeared detrimental. In summary, the periodic testing likely provided a partial exercise countermeasure for the quadriceps in the bedrest group, which is a novel finding given the extremely low exercise dose. The SPRINT exercise program appears to be viable for the quadriceps; however, refinement is needed to completely protect triceps surae myocellular and whole muscle health for astronauts on long-duration spaceflights.NEW & NOTEWORTHY This study provides unique exercise countermeasures development information for astronauts on long-duration spaceflights. The NASA SPRINT program was protective for quadriceps myocellular and whole muscle health, whereas the triceps surae (soleus) was only partially protected as has been shown with other programs. The bedrest control group data may provide beneficial information for overall exercise dose and targeting fast-twitch muscle fibers. Other unique approaches for the triceps surae are needed to supplement existing exercise programs.

Lower basal and postprandial muscle protein synthesis after 2 weeks single-leg immobilization in older men: No protective effect of anti-inflammatory medication.

Muscle inactivity may reduce basal and postprandial muscle protein synthesis (MPS) rates in humans. Anti-inflammatory treatment alleviates the MPS impairments in younger individuals. The present study explored the influence of nonsteroidal anti-inflammatory drugs (NSAIDs) upon MPS during a period of inactivity in older humans. Eighteen men (age 60-80 years) were allocated to ibuprofen (1200 mg/day, Ibu) or control (Plc) groups. One lower limb was cast immobilized for 2 weeks. Postabsorptive and postprandial MPS was measured before and after the immobilization by L-[ring-13 C6 ]-phenylalanine infusion. The protein expression of select anabolic signaling molecules was investigated by western blot. Basal (0.038 ± 0.002%/h and 0.039 ± 0.005%/h, Plc and Ibu, respectively) and postprandial (0.064 ± 0.004%/h and 0.067 ± 0.010%/h, Plc and Ibu, respectively) MPS rate were higher pre-immobilization compared to basal (0.019 ± 0.005%/h and 0.020 ± 0.010%/h, Plc and Ibu, respectively) and postprandial (0.033 ± 0.005%/h and 0.037 ± 0.006%/h, Plc and Ibu, respectively) MPS rate post-immobilization (p < 0.001). NSAID treatment did not affect the suppression of MPS (p > 0.05). The anabolic signaling were in general reduced after immobilization (p < 0.05). These changes were unaffected by NSAID treatment (p > 0.05). Basal and postprandial MPS dropped markedly after 2 weeks of lower limb immobilization. NSAID treatment neither influenced the reduction in MPS nor the anabolic signaling after immobilization in healthy older individuals.

Common Markers of Muscle Damage Are Associated with Divergent Gene Expression Patterns after Eccentric Contractions.

PURPOSE: Unaccustomed eccentric (ECC) exercise evokes exercise-induced muscle damage (EIMD). Soreness, strength loss, and serum creatine kinase (CK) are often used to quantify EIMD severity. However, changes in these markers are not fully understood mechanistically. To test the hypothesis that muscle damage markers are associated with unique molecular processes, we correlated gene expression responses with variation in each marker post-ECC. METHODS: Vastus lateralis biopsies were collected from 35 young men 3 h post-ECC (10 sets of 10 maximal eccentric contractions; contralateral leg [CON] as control). Maximal isometric strength, soreness, and serum CK activity were assessed 24 h preexercise and every 24 h for 5 d post-ECC. Strength was also measured 10 min post-ECC. Over the 5 d after ECC, average peak strength loss was 51.5 ± 20%; average soreness increased from 0.9 ± 1.9 on a 100-mm visual analog scale to 39 ± 19; serum CK increased from 160 ± 130 to 1168 ± 3430 U·L -1 . Muscle RNA was used to generate gene expression profiles. Partek Genomics Suite correlated peak values of soreness, strength loss, and CK post-ECC with gene expression in ECC (relative to paired CON) using Pearson linear correlation ( P < 0.05) and repeated-measures ANOVA used to detect influence of ECC. RESULTS: After ECC, 2677 genes correlated with peak soreness, 3333 genes with peak strength loss, and 3077 genes with peak CK. Less than 1% overlap existed across all markers (16/9087). Unique genes included 2346 genes for peak soreness, 3032 genes for peak strength loss, and 2937 genes for peak CK. CONCLUSIONS: The largely unique molecular pathways associated with common indirect markers of EIMD indicate that each marker of "damage" represents unique mechanistic processes.

Alleviation of peripheral sensitization by quadriceps insertion of cog polydioxanone filaments in knee osteoarthritis rats.

A recently established therapeutic strategy, involving the insertion of biodegradable cog polydioxanone filaments into the quadriceps muscles using the Muscle Enhancement and Support Therapy (MEST) device, has demonstrated significant efficacy in alleviating knee osteoarthritis (OA) pain. This study investigated changes in peripheral sensitization as the potential mechanism underlying MEST-induced pain relief in monoiodoacetate (MIA) induced OA rats. The results revealed that MEST treatment potently reduces MIA-induced sensitization of L3/L4 dorsal root ganglion (DRG) neurons, the primary nociceptor pathway for the knee joint. This reduction in DRG sensitization, as elucidated by voltage-sensitive dye imaging, is accompanied by a diminished overexpression of TRPA1 and NaV1.7, key nociceptor receptors involved in mechanical pain perception. Importantly, these observed alterations strongly correlate with a decrease in mechanically-evoked pain behaviors, providing compelling neurophysiological evidence that MEST treatment alleviates OA pain by suppressing peripheral sensitization.

Intermittent normobaric hypoxia alters substrate partitioning and muscle oxygenation in individuals with obesity: implications for fat burning.

This single-blind, crossover study aimed to measure and evaluate the short-term metabolic responses to continuous and intermittent hypoxic patterns in individuals with obesity. Indirect calorimetry was used to quantify changes in resting metabolic rate (RMR), carbohydrate (CHOox, %CHO), and fat oxidation (FATox, %FAT) in nine individuals with obesity pre and post: 1) breathing normoxic air [normoxic sham control (NS-control)], 2) breathing continuous hypoxia (CH), or 3) breathing intermittent hypoxia (IH). A mean peripheral oxygen saturation ([Formula: see text]) of 80-85% was achieved over a total of 45 min of hypoxia. Throughout each intervention, pulmonary gas exchanges, oxygen consumption (V̇o2) carbon dioxide production (V̇co2), and deoxyhemoglobin concentration (Δ[HHb]) in the vastus lateralis were measured. Both RMR and CHOox measured pre- and postinterventions were unchanged following each treatment: NS-control, CH, or IH (all P > 0.05). Conversely, a significant increase in FATox was evident between pre- and post-IH (+44%, P = 0.048). Although the mean Δ[HHb] values significantly increased during both IH and CH (P < 0.05), the greatest zenith of Δ[HHb] was achieved in IH compared with CH (P = 0.002). Furthermore, there was a positive correlation between Δ[HHb] and the shift in FATox measured pre- and postintervention. It is suggested that during IH, the increased bouts of muscle hypoxia, revealed by elevated Δ[HHb], coupled with cyclic periods of excess posthypoxia oxygen consumption (EPHOC, inherent to the intermittent pattern) played a significant role in driving the increase in FATox post-IH.

No Difference in Muscle Basal Oxygenation in a Bedridden Population Pre and Post Rehabilitation.

Long periods of bed rest for elderly population, due to a femur fracture event, can cause a deterioration in the muscular capacity. Therefore, monitoring of the muscle oxidative capacity in this fragile population is necessary to define the muscular oxidative metabolism state before and after a rehabilitation period. The time-domain near-infrared spectroscopy (TD-NIRS) technique enables the absolute values to be calculated for hemodynamic parameters such as oxy- (O2Hb), deoxy- (HHb), total- (tHb) haemoglobin, and tissue oxygen saturation (SO2) of the muscular tissue. In this work, we have characterized vastus lateralis muscle hemodynamics during a baseline period at two different time points: after the surgery (PRE) and after 15 days of rehabilitation (POST). The mean values for the absolute values of the hemodynamic parameters were: O2Hb_PRE = 49.1 ± 14.1 µM; O2Hb_POST = 47.1 ± 13.4 µM; HHb_PRE = 28.3 ± 10.3 µM; HHb_POST = 26.7 ± 9.9 µM; tHb_PRE = 77.3 ± 23.6 µM; tHb_POST = 73.8 ± 21.4 µM; SO2_PRE = 63.9 ± 4.0% and SO2_POST = 64.9 ± 5.6%. The hemodynamic parameters did not show significant differences at both group and single subject level. These results suggest that for this kind of population, the baseline of the hemodynamic parameters is not the best one to consider to assess the rehabilitation progresses in terms of muscular oxidative metabolism.

Relationship Between Muscle Deoxygenation and Cardiac Output in Subjects Without Attenuation of Deoxygenation Hemoglobin Concentration Near the End of Ramp Cycling Exercise: A Longitudinal Study.

The aim of this study was to investigate the longitudinal relationship between the slopes of systemic and quadriceps muscle O2 dynamics in subjects without attenuation point in deoxygenated hemoglobin concentration at vastus lateralis (APdeoxy-Hb@VL) during high-intensity cycling. Seven young men without APdeoxy-Hb@VL performed ramp cycling exercise until exhaustion before and after 8 weeks, while continuing recreational physical activities throughout that period. Muscle O2 saturation (SmO2) and deoxy-Hb were monitored at the vastus lateralis (VL) and rectus femoris (RF) by near infrared spectroscopy oximetry during exercise. Cardiac output (CO) was also continuously assessed. During high-intensity exercise, at VL, a significantly steeper slope of deoxy-Hb was found after 8 weeks compared with before, while the slopes of deoxy-Hb at RF were not significantly changed. Though a decrease in the slope of CO after 8 weeks did not reach significance (p = 0.12), the change in the slope of CO was significantly related to the change in the slopes of deoxy-Hb at VL (rs = -0.89, p < 0.01) and RF (rs = -0.86, p < 0.05). Our data reinforces the idea that, in subjects without APdeoxy-Hb@VL, the slope of muscle deoxygenation at VL during high-intensity cycling exercise may partly be explained by systemic O2 supply, rather than O2 balance in other thigh muscles.

No net utilization of intramuscular lipid droplets during repeated high-intensity intermittent exercise.

Intramuscular lipids are stored as subsarcolemmal or intramyofibrillar droplets with potential diverse roles in energy metabolism. We examined intramuscular lipid utilization through transmission electron microscopy during repeated high-intensity intermittent exercise, an aspect that is hitherto unexplored. Seventeen moderately to well-trained males underwent three periods (EX1-EX3) of 10 × 45-s high-intensity cycling [∼100%-120% Wattmax (Wmax)] combined with maximal repeated sprints (∼250%-300% Wmax). M. vastus lateralis biopsies were obtained at baseline, after EX1, and EX3. During the complete exercise session, no net decline in either subsarcolemmal or intermyofibrillar lipid volume density occurred. However, a temporal relationship emerged for subsarcolemmal lipids with an ∼11% increase in droplet size after EX1 (P = 0.024), which reverted to baseline levels after EX3 accompanied by an ∼30% reduction in the numerical density of subsarcolemmal lipid droplets compared with both baseline (P = 0.019) and after EX1 (P = 0.018). Baseline distinctions were demonstrated with an approximately twofold higher intermyofibrillar lipid volume in type 1 versus type 2 fibers (P = 0.008), mediated solely by a higher number rather than the size of lipid droplets (P < 0.001). No fiber-type-specific differences were observed in subsarcolemmal lipid volume although type 2 fibers exhibited ∼17% larger droplets (P = 0.034) but a lower numerical density (main effect; P = 0.010) including 3% less droplets at baseline. Collectively, these findings suggest that intramuscular lipids do not serve as an important substrate during high-intensity intermittent exercise; however, the repeated exercise pattern mediated a temporal remodeling of the subsarcolemmal lipid pool. Furthermore, fiber-type- and compartment-specific differences were found at baseline underscoring the heterogeneity in lipid droplet deposition.NEW & NOTEWORTHY Undertaking a severe repeated high-intensity intermittent exercise protocol led to no net decline in neither subsarcolemmal nor intermyofibrillar lipid content in the thigh muscle of young moderately to well-trained participants. However, a temporal remodeling of the subsarcolemmal pool of lipid droplets did occur indicative of potential transient lipid accumulation. Moreover, baseline fiber-type distinctions in subcellular lipid droplet deposition were present underscoring the diversity in lipid droplet storage among fiber types and subcellular regions.

Effect of sit-to-stand-based training on muscle quality in sedentary adults: a randomized controlled trial.

The aim of this study was to compare the effects of sit-to-stand (STS) training programs with 5 vs. 10 repetitions on muscle architecture and muscle function in sedentary adults. Sixty participants were randomly assigned into three groups: five-repetition STS (5STS), 10-repetition STS (10STS), or a control group (CG). Participants performed three sets of five or 10 repetitions of the STS exercise three times per week for 8 weeks. Before and after 8 weeks, all groups performed ultrasound measures to evaluate muscle thickness (MT), pennation angle (PA), and fascicle length (FL), and the five-repetition STS test to estimate the relative STS power and muscle quality index (MQI). After 8 weeks, both experimental groups improved MQI (40-45%), relative STS power (29-38%), and MT (8-9%) (all p < 0.001; no differences between the 5STS vs. 10STS groups). These improvements in both groups resulted in differences regarding the CG, which did not present any change. In addition, only the 5STS group improved PA (15%; p = 0.008) without differences to the 10STS and CG.This suggests that STS training is time-effective and low-cost for improving muscle function and generating adaptations in muscle architecture.

Vicia faba Peptide Network Supplementation Does Not Differ From Milk Protein in Modulating Changes in Muscle Size During Short-Term Immobilization and Subsequent Remobilization, but Increases Muscle Protein Synthesis Rates During Remobilization in Healthy Young Men.

BACKGROUND: Muscle mass and strength decrease during short periods of immobilization and slowly recover during remobilization. Recent artificial intelligence applications have identified peptides that appear to possess anabolic properties in in vitro assays and murine models. OBJECTIVES: This study aimed to compare the impact of Vicia faba peptide network compared with milk protein supplementation on muscle mass and strength loss during limb immobilization and regain during remobilization. METHODS: Thirty young (24 ± 5 y) men were subjected to 7 d of one-legged knee immobilization followed by 14 d of ambulant recovery. Participants were randomly allocated to ingest either 10 g of the Vicia faba peptide network (NPN_1; n = 15) or an isonitrogenous control (milk protein concentrate; MPC; n = 15) twice daily throughout the study. Single-slice computed tomography scans were performed to assess quadriceps cross-sectional area (CSA). Deuterium oxide ingestion and muscle biopsy sampling were applied to measure myofibrillar protein synthesis rates. RESULTS: Leg immobilization decreased quadriceps CSA (primary outcome) from 81.9 ± 10.6 to 76.5 ± 9.2 cm2 and from 74.8 ± 10.6 to 71.5 ± 9.8 cm2 in the NPN_1 and MPC groups, respectively (P < 0.001). Remobilization partially recovered quadriceps CSA (77.3 ± 9.3 and 72.6 ± 10.0 cm2, respectively; P = 0.009), with no differences between the groups (P > 0.05). During immobilization, myofibrillar protein synthesis rates (secondary outcome) were lower in the immobilized leg (1.07% ± 0.24% and 1.10% ± 0.24%/d, respectively) than in the non-immobilized leg (1.55% ± 0.27% and 1.52% ± 0.20%/d, respectively; P < 0.001), with no differences between the groups (P > 0.05). During remobilization, myofibrillar protein synthesis rates in the immobilized leg were greater with NPN_1 than those with MPC (1.53% ± 0.38% vs. 1.23% ± 0.36%/d, respectively; P = 0.027). CONCLUSION: NPN_1 supplementation does not differ from milk protein in modulating the loss of muscle size during short-term immobilization and the regain during remobilization in young men. NPN_1 supplementation does not differ from milk protein supplementation in modulating the myofibrillar protein synthesis rates during immobilization but further increases myofibrillar protein synthesis rates during remobilization.

Muscle oxygen saturation rates coincide with lactate-based exercise thresholds.

INTRODUCTION: Monitoring muscle metabolic activity via blood lactate is a useful tool for understanding the physiological response to a given exercise intensity. Recent indications suggest that skeletal muscle oxygen saturation (SmO2), an index of the balance between local O2 supply and demand, may describe and predict endurance performance outcomes. PURPOSE: We tested the hypothesis that SmO2 rate is tightly related to blood lactate concentration across exercise intensities, and that deflections in SmO2 rate would coincide with established blood lactate thresholds (i.e., lactate thresholds 1 and 2). METHODS: Ten elite male soccer players completed an incremental running protocol to exhaustion using 3-min work to 30 s rest intervals. Blood lactate samples were collected during rest and SmO2 was collected continuously via near-infrared spectroscopy from the right and left vastus lateralis, left biceps femoris and the left gastrocnemius. RESULTS: Muscle O2 saturation rate (%/min) was quantified after the initial 60 s of each 3-min segment. The SmO2 rate was significantly correlated with blood lactate concentrations for all muscle sites; RVL, r = - 0.974; LVL, r = - 0.969; LG, r = - 0.942; LHAM, r = - 0.907. Breakpoints in SmO2 rate were not significantly different from LT1 or LT2 at any muscle sites (P > 0.05). Bland-Altman analysis showed speed threshold estimates via SmO2 rate and lactate are similar at LT2, but slightly greater for SmO2 rate at LT1. CONCLUSIONS: Muscle O2 saturation rate appears to provide actionable information about maximal metabolic steady state and is consistent with bioenergetic reliance on oxygen and its involvement in the attainment of metabolic steady state.

Multitissue responses to exercise: a MoTrPAC feasibility study.

We assessed the feasibility of the Molecular Transducers of Physical Activity Consortium (MoTrPAC) human adult clinical exercise protocols, while also documenting select cardiovascular, metabolic, and molecular responses to these protocols. After phenotyping and familiarization sessions, 20 subjects (25 ± 2 yr, 12 M, 8 W) completed an endurance exercise bout (n = 8, 40 min cycling at 70% V̇o2max), a resistance exercise bout (n = 6, ∼45 min, 3 sets of ∼10 repetition maximum, 8 exercises), or a resting control period (n = 6, 40 min rest). Blood samples were taken before, during, and after (10 min, 2 h, and 3.5 h) exercise or rest for levels of catecholamines, cortisol, glucagon, insulin, glucose, free fatty acids, and lactate. Heart rate was recorded throughout exercise (or rest). Skeletal muscle (vastus lateralis) and adipose (periumbilical) biopsies were taken before and ∼4 h following exercise or rest for mRNA levels of genes related to energy metabolism, growth, angiogenesis, and circadian processes. Coordination of the timing of procedural components (e.g., local anesthetic delivery, biopsy incisions, tumescent delivery, intravenous line flushes, sample collection and processing, exercise transitions, and team dynamics) was reasonable to orchestrate while considering subject burden and scientific objectives. The cardiovascular and metabolic alterations reflected a dynamic and unique response to endurance and resistance exercise, whereas skeletal muscle was transcriptionally more responsive than adipose 4 h postexercise. In summary, the current report provides the first evidence of protocol execution and feasibility of key components of the MoTrPAC human adult clinical exercise protocols. Scientists should consider designing exercise studies in various populations to interface with the MoTrPAC protocols and DataHub.NEW & NOTEWORTHY This study highlights the feasibility of key aspects of the MoTrPAC adult human clinical protocols. This initial preview of what can be expected from acute exercise trial data from MoTrPAC provides an impetus for scientists to design exercise studies to interlace with the rich phenotypic and -omics data that will populate the MoTrPAC DataHub at the completion of the parent protocol.

Menopause Transition: A Cross-Sectional Evaluation on Muscle Size and Quality.

INTRODUCTION: The menopause transition yields significant physiological alterations. The purpose was to characterize lean soft tissue (LST), muscle size (muscle cross-sectional area (mCSA)), muscle quality (echo intensity (EI)), and strength across the menopause transition. A secondary aim was to evaluate whole-body protein turnover in a subsample of women. METHODS: Seventy-two healthy women were enrolled in this cross-sectional study based on menopause stage (PRE: n = 24; PERI: n = 24; POST: n = 24). Whole-body LST was measured via dual-energy x-ray absorptiometry, and muscle characteristics (mCSA and EI) were measured via B-mode ultrasound of the vastus lateralis. Maximal voluntary contractions (N·m) of the knee extensors were evaluated. Physical activity (in minutes per day) was accounted for using the International Physical Activity Questionnaire. A subsample of women ( n = 27) ingested 2.0 g of 15 N-alanine to determine whole-body net protein balance (NB; in grams per kilogram of body mass per day). RESULTS: Significant differences were evident in LST ( P = 0.022), leg LST ( P = 0.05), and EI ( P = 0.018) between menopause stages. Bonferroni post-hoc comparisons revealed greater LST in PRE versus PERI (mean difference (MD) ± SE, 3.8 ± 1.5 kg; P = 0.048) and POST (3.9 ± 1.5 lb; P = 0.049). Similarly, EI was significantly higher in PERI PRE (MD, 18.3 ± 7.1 a.u.; P = 0.036). There was no significant difference in mCSA ( P = 0.082) or in maximal voluntary contraction ( P = 0.167). NB was significantly different across groups ( P = 0.026); NB was greater in PRE compared with PERI (MD, 0.39 ± 0.17 g·kg -1 ; P = 0.090), and from PRE to POST (MD, 0.46 ± 0.17 g·kg -1 ; P = 0.042). Physical activity was not significantly different across groups but demonstrated a linear increase from PRE to POST. CONCLUSIONS: The current findings suggest that LST, muscle quality, and protein balance may be negatively influenced by the menopause transition.

Extracellular matrix content and remodeling markers do not differ in college-aged men classified as higher and lower responders to resistance training.

We determined if skeletal muscle extracellular matrix (ECM) content and remodeling markers adapted with resistance training or were associated with hypertrophic outcomes. Thirty-eight untrained males (21 ± 3 yr) participated in whole body resistance training (10 wk, 2 × weekly). Participants completed testing [ultrasound, peripheral quantitative computed tomography (pQCT)] and donated a vastus lateralis (VL) biopsy 1 wk before training and 72 h following the last training bout. Higher responders (HR, n = 10) and lower responders (LR, n = 10) were stratified based on a composite score considering changes in pQCT-derived mid-thigh cross-sectional area (mCSA), ultrasound-derived VL thickness, and mean fiber cross-sectional area (fCSA). In all participants, training reduced matrix metalloprotease (MMP)-14 protein (P < 0.001) and increased satellite cell abundance (P < 0.001); however, VL fascial thickness, ECM protein content per myofiber, MMP-2/-9 protein content, tissue inhibitor of metalloproteinase (TIMP)-1/-2 protein content, collagen-1/-4 protein content, macrophage abundance, or fibroadipogenic progenitor cell abundance were not altered. Regarding responder analysis, MMP-14 exhibited an interaction (P = 0.007), and post hoc analysis revealed higher protein content in HR versus LR before training (P = 0.026) and a significant decrease from pre to posttraining in HR only (P = 0.002). In summary, basal skeletal muscle ECM markers are minimally affected with 10 wk of resistance training, and these findings could be related to not capturing more dynamic alterations in the assayed markers earlier in training. However, the downregulation in MMP-14 in college-aged men classified as HR is a novel finding and warrants continued investigation, and further research is needed to delineate muscle connective tissue strength attributes between HR and LR.NEW & NOTEWORTHY Although past studies have examined aspects of extracellular matrix remodeling in relation to mechanical overload or resistance training, this study serves to expand our knowledge on a multitude of extracellular matrix markers and whether these markers adapt to resistance training or are associated with differential hypertrophic responses.