Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study.

RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

Robust arm and leg muscle adaptation to training despite ACE inhibition: a randomized placebo-controlled trial.

PURPOSE: Angiotensin-converting enzyme (ACE) inhibitor treatment is widely applied, but the fact that plasma ACE activity is a potential determinant of training-induced local muscular adaptability is often neglected. Thus, we investigated the hypothesis that ACE inhibition modulates the response to systematic aerobic exercise training on leg and arm muscular adaptations. METHODS: Healthy, untrained, middle-aged participants (40 ± 7 yrs) completed a randomized, double-blinded, placebo-controlled trial. Participants were randomized to placebo (PLA: CaCO3) or ACE inhibitor (ACEi: enalapril) for 8 weeks and completed a supervised, high-intensity exercise training program. Muscular characteristics in the leg and arm were extensively evaluated pre and post-intervention. RESULTS: Forty-eight participants (nACEi = 23, nPLA = 25) completed the trial. Exercise training compliance was above 99%. After training, citrate synthase, 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity were increased in m. vastus lateralis in both groups (all P < 0.05) without statistical differences between them (all time × treatment P > 0.05). In m. deltoideus, citrate synthase maximal activity was upregulated to a greater extent (time × treatment P < 0.05) in PLA (51 [33;69] %) than in ACEi (28 [13;43] %), but the change in 3-hydroxyacyl-CoA dehydrogenase and phosphofructokinase maximal activity was similar between groups. Finally, the training-induced changes in the platelet endothelial cell adhesion molecule-1 protein abundance, a marker of capillary density, were similar in both groups in m. vastus lateralis and m. deltoideus. CONCLUSION: Eight weeks of high-intensity whole-body exercise training improves markers of skeletal muscle mitochondrial oxidative capacity, glycolytic capacity and angiogenesis, with no overall effect of pharmacological ACE inhibition in healthy adults.

Near-infrared spectroscopy-derived muscle V̇O2${\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ kinetics after moderate running exercise in healthy males: reliability and associations with parameters of aerobic fitness.

NEW FINDINGS: What is the central question of this study? What is the reliability of near-infrared spectroscopy-derived muscle oxygen uptake ( mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ ) kinetics following running exercise and what is the relationship between the time constant of mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ off-kinetics and parameters of aerobic fitness? What is the main finding and its importance? The time constant of mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ kinetics in gastrocnemius following moderate running exercise presents good to excellent reliability. In addition, it was well correlated with parameters of aerobic fitness, such as maximal speed of an incremental test, ventilatory threshold and pulmonary V̇O2${\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ on-kinetics. Therefore, near-infrared spectroscopy-derived muscle oxidative capacity together with other physiological measurements may allow a concomitant local and systemic analysis of the components of the oxidative system. ABSTRACT: Near-infrared spectroscopy-derived muscle oxygen uptake ( mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ ) kinetics following single-joint exercise has been used to assess muscle oxidative capacity. However, little evidence is available on the use of this technique following whole-body exercise. Therefore, this study aimed to assess the reliability of the NIRS-derived mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ kinetics following running exercise and to investigate the relationship between the time constant of mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ off-kinetics ( τmV̇O2$\tau {\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ ) and parameters of aerobic fitness. After an incremental test to determine V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ , first (VT1 ) and second (VT2 ) ventilatory thresholds, and maximal speed (Smax ), 13 males (age = 21 ± 4 years; V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 55.9 ± 3.4 ml kg-1  min-1 ) performed three sets (two on the first day and one on a subsequent day) of two repetitions of 6-min running exercise at 90%VT1 . The pulmonary V̇O2${\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ ( pV̇O2${\rm{p}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ ) on-kinetics and mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ off-kinetics in gastrocnemius were assessed. τmV̇O2$\tau {\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ presented no systematic change and satisfactory reliability (the standard error of the measurement (SEM) and intraclass correlation coefficient of 4.21 s and 0.49 for between transitions; and 2.65 s and 0.74 averaging τmV̇O2$\tau {\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ within each time set), with no difference (P > 0.3) between the within- (SEM = 2.92 s) and between-day variability (SEM = 2.78 s and 2.19 s between first vs. third set, and second vs. third set, respectively). τmV̇O2$\tau {\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ (28.5 ± 4.17 s) correlated significantly (P < 0.05) with Smax (r = -0.66), VT1 (r = -0.64) and time constant of the p V̇O2${\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ on-kinetics (r = 0.69). These findings indicate that NIRS-derived mV̇O2${\rm{m}}{\dot{V}_{{{\rm{O}}_{\rm{2}}}}}$ kinetics in the gastrocnemius following moderate running exercise is a useful and reliable parameter to assess muscle oxidative capacity.

Validity and accuracy of calculating oxidative ATP synthesis in vivo during high-intensity skeletal muscle contractions.

Several methods have been developed for using 31 P-MRS to calculate rates of oxidative ATP synthesis (ATPOX ) during muscular contractions based on assumptions that (1) the ATP cost of force generation (ATPCOST ) remains constant or (2) Michaelis-Menten coupling between cytosolic ADP and ATPOX does not change. However, growing evidence suggests that one, or both, of these assumptions are invalid during high-intensity fatigue protocols. Consequently, there is a need to examine the validity and accuracy of traditional ATPOX calculation methods under these conditions. To address this gap, we measured phosphate concentrations and pH in the vastus lateralis muscle of nine young adults during four rest-contraction-recovery trials lasting 24, 60, 120, and 240 s. The initial velocity of phosphocreatine resynthesis (ViPCr ) following each trial served as the criterion measure of ATPOX because this method makes no assumptions of constant ATPCOST or Michaelis-Menten coupling between changes in cytosolic ADP and ATPOX . Subsequently, we calculated ATPOX throughout the 240 s trial using several traditional calculation methods and compared estimations of ATPOX from each method with time-matched measurements of ViPCr . Method 1, which assumes that ATPCOST does not change, was able to model changes in ViPCr over time, but showed poor accuracy for predicting ViPCr across a wide range of ATPOX values. In contrast, Michaelis-Menten methods, which assume that the relationship between changes in cytosolic ADP and ATPOX remains constant, were invalid because they could not model the decline in ViPCr . However, adjusting these Michaelis-Menten methods for observed changes in maximal ATPOX capacity (i.e., Vmax ) permitted modeling of the decline in ViPCr and markedly improved accuracy. The results of these comprehensive analyses demonstrate that valid, accurate measurements of ATPOX can be obtained during high-intensity contractions by adjusting Michaelis-Menten ATPOX calculations for changes in Vmax observed from baseline to post-fatigue.

Skeletal muscle and performance adaptations to high-intensity training in elite male soccer players: speed endurance runs versus small-sided game training.

PURPOSE: To examine the skeletal muscle and performance responses across two different exercise training modalities which are highly applied in soccer training. METHODS: Using an RCT design, 39 well-trained male soccer players were randomized into either a speed endurance training (SET; n = 21) or a small-sided game group (SSG; n = 18). Over 4 weeks, thrice weekly, SET performed 6-10 × 30-s all-out runs with 3-min recovery, while SSG completed 2 × 7-9-min small-sided games with 2-min recovery. Muscle biopsies were obtained from m. vastus lateralis pre and post intervention and were subsequently analysed for metabolic enzyme activity and muscle protein expression. Moreover, the Yo-Yo Intermittent Recovery level 2 test (Yo-Yo IR2) was performed. RESULTS: Muscle CS maximal activity increased (P < 0.05) by 18% in SET only, demonstrating larger (P < 0.05) improvement than SSG, while HAD activity increased (P < 0.05) by 24% in both groups. Na+-K+ ATPase α1 subunit protein expression increased (P < 0.05) in SET and SSG (19 and 37%, respectively), while MCT4 protein expression rose (P < 0.05) by 30 and 61% in SET and SSG, respectively. SOD2 protein expression increased (P < 0.05) by 28 and 37% in SET and SSG, respectively, while GLUT-4 protein expression increased (P < 0.05) by 40% in SSG only. Finally, SET displayed 39% greater improvement (P < 0.05) in Yo-Yo IR2 performance than SSG. CONCLUSION: Speed endurance training improved muscle oxidative capacity and exercise performance more pronouncedly than small-sided game training, but comparable responses were in muscle ion transporters and antioxidative capacity in well-trained male soccer players.

Endurance neuromuscular electrical stimulation training improves skeletal muscle oxidative capacity in individuals with motor-complete spinal cord injury.

INTRODUCTION: Spinal cord injury (SCI) results in skeletal muscle atrophy, increases in intramuscular fat, and reductions in skeletal muscle oxidative capacity. Endurance training elicited with neuromuscular electrical stimulation (NMES) may reverse these changes and lead to improvement in muscle metabolic health. METHODS: Fourteen participants with complete SCI performed 16 weeks of home-based endurance NMES training of knee extensor muscles. Skeletal muscle oxidative capacity, muscle composition, and blood metabolic and lipid profiles were assessed pre- and post-training. RESULTS: There was an increase in number of contractions performed throughout the duration of training. The average improvement in skeletal muscle oxidative capacity was 119%, ranging from -14% to 387% (P = 0.019). There were no changes in muscle composition or blood metabolic and lipid profiles. CONCLUSION: Endurance training improved skeletal muscle oxidative capacity, but endurance NMES of knee extensor muscles did not change blood metabolic and lipid profiles. Muscle Nerve 55: 669-675, 2017.

Relationship between skeletal mitochondrial function and digital markers of free-living physical activity in older adults.

This study examined the association between in vivo skeletal mitochondrial function and digital free-living physical activity patterns-a measure that summarizes biological, phenotypic, functional, and environmental effects on mobility. Among 459 participants (mean age 68 years; 55% women) in the Baltimore Longitudinal Study of Aging, mitochondrial function was quantified as skeletal muscle oxidative capacity via post-exercise phosphocreatine recovery rate (τPCr) in the vastus lateralis muscle of the left thigh, using 31P magnetic resonance spectroscopy. Accelerometry was collected using a 7-day, 24-h wrist-worn protocol and summarized into activity amount, intensity, endurance, and accumulation patterning metrics. Linear regression, two-part linear and logistic (bout analyses), and linear mixed effects models (time-of-day analyses) were used to estimate associations between τPCr and each physical activity metric. Interactions by age, sex, and gait speed were tested. After covariate adjustment, higher τPCr (or poorer mitochondrial function) was associated with lower activity counts/day (ß = - 6593.7, SE = 2406.0; p = 0.006) and activity intensity (- 81.5 counts, SE = 12.9; p < 0.001). For activity intensity, the magnitude of association was greater for men and those with slower gait speed (interaction p < 0.02 for both). Conversely, τPCr was not associated with daily active minutes/day (p = 0.15), activity fragmentation (p = 0.13), or endurance at any bout length (p > 0.05 for all). Time-of-day analyses show participants with high τPCr were less active from 6:00 a.m. to 12:00 a.m. than those with low τPCr. Results indicate that poorer skeletal mitochondrial function is primarily associated with lower engagement in high intensity activities. Our findings help define the connection between laboratory-measured mitochondrial function and real-world physical activity behavior.

Maximal Oxygen Uptake, Muscular Oxidative Capacity, and Ventilatory Threshold in Amateur Triathletes: Eight-Month Training Follow-Up.

Purpose: Endurance sports performance is influenced by several factors, including maximal oxygen uptake (⩒O2max), the percentage of ⩒O2max that can be sustained in endurance events, running economy, and body composition. Traditionally, ⩒O2max can be measured as an absolute value, adjusted for body mass, reflecting the athlete's central capacity (maximal cardiac output), or adjusted for lean mass (LM), reflecting the athlete's peripheral capacity (muscular oxidative capacity). The present study aims to evaluate absolute, total body mass, and lower limb LM-adjusted ⩒O2max, ventilatory thresholds (VT), respiratory compensation points (RCP), and body composition during two training periods separated by 8 months. Patients and Methods: Thirteen competitive amateur triathletes [seven men (40.7±13.7 years old, 76.3±8.3kg, and 173.9±4.8cm) and six women (43.5±6.9 years old, 55.0±2.7kg, 164.9±5.2cm)] were evaluated for body composition with dual-energy X-ray absorptiometry and ⩒O2max, VT, RPC, and maximal aerobic speed (MAS) with a cardiorespiratory maximal treadmill test. Results: The absolute ⩒O2max (p = 0.003, d = 1.05), body mass-adjusted ⩒O2max (p < 0.001, d = 1.2859), and MAS (p = 0.047, d = 0.6139) values differed significantly across evaluation periods. Lower limb LM-adjusted ⩒O2max (p = 0.083, d = -0.0418), %⩒O2max at VT (p = 0.541, d = -0.1746), speed at VT (p = 0.337, d = -0.2774), % ⩒O2max at RCP (p = 0.776, d = 0.0806), and speed at RCP (p = 0.436, d = 0.2234) showed no difference. Conclusion: The sensitivities of ⩒O2max adjusted for body mass and ⩒O2max adjusted for LM to detect changes in physical training state differ. Furthermore, decreases in physical fitness level, as evaluated by ⩒O2max values, are not accompanied by changes in VT.

The influence of sex, hemoglobin mass, and skeletal muscle characteristics on cycling critical power.

Critical power (CP) represents an important threshold for exercise performance and fatiguability. We sought to determine the extent to which sex, hemoglobin mass (Hbmass), and skeletal muscle characteristics influence CP. Before CP determination (i.e., 3-5 constant work rate trials to task failure), Hbmass and skeletal muscle oxidative capacity (τ) were measured and vastus lateralis (VL) muscle biopsy samples were collected from 12 females and 12 males matched for aerobic fitness relative to fat-free mass (FFM) [means (SD); V̇o2max: 59.2 (7.7) vs. 59.5 (7.1) mL·kg·FFM-1·min-1, respectively]. Males had a significantly greater CP than females in absolute units [225 (28) vs. 170 (43) W; P = 0.001] but not relative to body mass [3.0 (0.6) vs. 2.7 (0.6) W·kg·BM-1; P = 0.267] or FFM [3.6 (0.7) vs. 3.7 (0.8) W·kg·FFM-1; P = 0.622]. Males had significantly greater W' (P ≤ 0.030) and greater Hbmass (P ≤ 0.016) than females, regardless of the normalization approach; however, there were no differences in mitochondrial protein content (P = 0.375), τ (P = 0.603), or MHC I proportionality (P = 0.574) between males and females. Whether it was expressed in absolute or relative units, CP was positively correlated with Hbmass (0.444 ≤ r ≤ 0.695; P < 0.05), mitochondrial protein content (0.413 ≤ r ≤ 0.708; P < 0.05), and MHC I proportionality (0.506 ≤ r ≤ 0.585; P < 0.05), and negatively correlated with τ when expressed in relative units only (-0.588 ≤ r ≤ -0.527; P < 0.05). Overall, CP was independent of sex, but variability in CP was related to Hbmass and skeletal muscle characteristics. The extent to which manipulations in these physiological parameters influence CP warrants further investigation to better understand the factors underpinning CP.NEW & NOTEWORTHY In males and females matched for aerobic fitness [maximal oxygen uptake normalized to fat-free mass (FFM)], absolute critical power (CP) was greater in males, but relative CP (per kilogram body mass or FFM) was similar between sexes. CP correlated with hemoglobin mass, mitochondrial protein content, myosin heavy chain type I proportion, and skeletal muscle oxidative capacity. These findings demonstrate the importance of matching sexes for aerobic fitness, but further experiments are needed to determine causality.

Association of skeletal muscle oxidative capacity with muscle function, sarcopenia-related exercise performance, and intramuscular adipose tissue in older adults.

Muscle function and exercise performance measures, such as muscle endurance capacity, maximal strength, chair stand score, gait speed, and Timed Up and Go score, are evaluated to diagnose sarcopenia and frailty in older individuals. Furthermore, intramuscular adipose tissue (IntraMAT) content increases with age. Skeletal muscle oxidative capacity determines muscle metabolism and maintains muscle performance. This study aimed to investigate the association of skeletal muscle oxidative capacity with muscle function, exercise performance, and IntraMAT content in older individuals. Thirteen older men and women participated in this study. Skeletal muscle oxidative capacity was assessed by the recovery speed of muscle oxygen saturation after exercise using near-infrared spectroscopy from the medial gastrocnemius. We assessed two muscle functions, peak torque and time to task failure, and four sarcopenia-related exercise performances: handgrip strength, gait speed, 30-s chair stand, and Timed Up and Go. The IntraMAT content was measured using axial magnetic resonance imaging. The results showed a relationship between skeletal muscle oxidative capacity and gait speed but not with muscle functions and other exercise performance measures. Skeletal muscle oxidative capacity was not related to IntraMAT content. Skeletal muscle oxidative capacity, which may be indicative of the capacity of muscle energy production in the mitochondria, is related to locomotive functions but not to other functional parameters or skeletal fat infiltration.

Effects of exercise-induced intracellular acidosis on the phosphocreatine recovery kinetics: a 31P MRS study in three muscle groups in humans.

Little is known about the metabolic differences that exist among different muscle groups within the same subjects. Therefore, we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to investigate muscle oxidative capacity and the potential effects of pH on PCr recovery kinetics between muscles of different phenotypes (quadriceps (Q), finger (FF) and plantar flexors (PF)) in the same cohort of 16 untrained adults. The estimated muscle oxidative capacity was lower in Q (29 ± 12 mM min(-1), CV(inter-subject) = 42%) as compared with PF (46 ± 20 mM min(-1), CV(inter-subject) = 44%) and tended to be higher in FF (43 ± 35 mM min(-1), CV(inter-subject) = 80%). The coefficient of variation (CV) of oxidative capacity between muscles within the group was 59 ± 24%. PCr recovery time constant was correlated with end-exercise pH in Q (p < 0.01), FF (p < 0.05) and PF (p < 0.05) as well as proton efflux rate in FF (p < 0.01), PF (p < 0.01) and Q (p = 0.12). We also observed a steeper slope of the relationship between end-exercise acidosis and PCr recovery kinetics in FF compared with either PF or Q muscles. Overall, this study supports the concept of skeletal muscle heterogeneity by revealing a comparable inter- and intra-individual variability in oxidative capacity across three skeletal muscles in untrained individuals. These findings also indicate that the sensitivity of mitochondrial respiration to the inhibition associated with cytosolic acidosis is greater in the finger flexor muscles compared with locomotor muscles, which might be related to differences in permeability in the mitochondrial membrane and, to some extent, to proton efflux rates.

Forearm muscle mitochondrial capacity and resting oxygen uptake: Relationship to symptomatic fatigue in persons with multiple sclerosis.

BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of multiple sclerosis (MS). Whether mitochondrial alterations are a function of ambulatory dysfunction or are of a non-ambulatory systemic nature is unclear. OBJECTIVE: To compare oxidative capacity, and rest muscle oxygen consumption (mVO2) in the upper limb of persons with multiple sclerosis (PwMS) to a control group (CON), whereby an upper limb would be comparatively independent of ambulation or deconditioning. METHODS: Near infra-red spectroscopy was used to measure oxidative capacity of the wrist flexors in PwMS (n = 16) and CON (n = 13). Oxidative capacity was indicated by the time constant (TC) of mVO2 recovery following brief wrist flexion contractions. Measurements included well-being, depression, symptomatic fatigue, disability, handgrip strength, cognition, and functional endurance. Analysis was by T-tests and Pearson correlations with p ≤ 0.05. Data are mean (SD). RESULTS: TC of mVO2 recovery was slower in PwMS (MS = 47(14) sec, CON = 36(11) sec; p = 0.03). No significant correlations were found between oxidative capacity and any other measures. Rest mVO2 was not different between groups, but correlated with symptomatic fatigue (r = 0.694, p = 0.003) and strength (0.585, p = 0.017) in PwMS. CONCLUSION: Oxidative capacity was lower in the wrist flexors of PwMS, possibly indicating a systemic component of the disease. Within PwMS, rest mVO2 was associated with symptomatic fatigue.

Protein supplementation elicits greater gains in maximal oxygen uptake capacity and stimulates lean mass accretion during prolonged endurance training: a double-blind randomized controlled trial.

BACKGROUND: Endurance training induces numerous cardiovascular and skeletal muscle adaptations, thereby increasing maximal oxygen uptake capacity (VO2max). Whether protein supplementation enhances these adaptations remains unclear. OBJECTIVE: The present study was designed to determine the impact of protein supplementation on changes in VO2max during prolonged endurance training. METHODS: We used a double-blind randomized controlled trial with repeated measures among 44 recreationally active, young males. Subjects performed 3 endurance training sessions per week for 10 wk. Supplements were provided immediately after each exercise session and daily before sleep, providing either protein (PRO group; n = 19; 21.5 ± 0.4 y) or an isocaloric amount of carbohydrate as control (CON group; n = 21; 22.5 ± 0.5 y). The VO2max, simulated 10-km time trial performance, and body composition (dual-energy X-ray absorptiometry) were measured before and after 5 and 10 wk of endurance training. Fasting skeletal muscle tissue samples were taken before and after 5 and 10 wk to measure skeletal muscle oxidative capacity, and fasting blood samples were taken every 2 wk to measure hematological factors. RESULTS: VO2max increased to a greater extent in the PRO group than in the CON group after 5 wk (from 49.9 ± 0.8 to 54.9 ± 1.1 vs 50.8 ± 0.9 to 53.0 ± 1.1 mL · kg-1 · min-1; P < 0.05) and 10 wk (from 49.9 ± 0.8 to 55.4 ± 0.9 vs 50.8 ± 0.9 to 53.9 ± 1.2 mL · kg-1 · min-1; P < 0.05). Lean body mass increased in the PRO group whereas lean body mass in the CON group remained stable during the first 5 wk (1.5 ± 0.2 vs 0.1 ± 0.3 kg; P < 0.05) and after 10 wk (1.5 ± 0.3 vs 0.4 ± 0.3 kg; P < 0.05). Throughout the intervention, fat mass reduced significantly in the PRO group and there were no changes in the CON group after 5 wk (-0.6 ± 0.2 vs -0.1 ± 0.2 kg; P > 0.05) and 10 wk (-1.2 ± 0.4 vs -0.2 ± 0.2 kg; P < 0.05). CONCLUSIONS: Protein supplementation elicited greater gains in VO2max and stimulated lean mass accretion but did not improve skeletal muscle oxidative capacity and endurance performance during 10 wk of endurance training in healthy, young males. This trial was registered at clinicaltrials.gov as NCT03462381.

Effects of Repeated, Long-Duration Hyperoxic Water Immersions on Neuromuscular Endurance in Well-Trained Males.

PURPOSE: This study examined the effects of repeated long-duration hyperoxic water immersions (WIs) at 1.35 atmospheres absolute (ATA) on neuromuscular endurance performance. We hypothesized that over a 5-day period of consecutive, resting, long-duration hyperoxic WIs there would be a decrease to neuromuscular endurance performance and tissue oxygenation with the quadriceps muscle, but not with the forearm flexors. METHODS: Thirteen well-trained, male subjects completed five consecutive 6-h resting WIs with 18-h surface intervals during the dive week while breathing 100% oxygen at 1.35 ATA. We assessed skeletal muscle endurance performance before and after each WI, and 24 and 72 h after the final WI. Muscular endurance assessments included 40% maximal handgrip endurance (MHE) and 50-repetition maximal isokinetic (IK) knee extensions. Near-infrared spectroscopy (NIRS) was used to measure muscle oxidative capacity (MOC) of the vastus lateralis and localized muscle tissue oxygenation of the vastus lateralis and flexor carpi radialis. Simultaneously, we measured brachioradialis neuromuscular activation by surface electromyography (SEMG). RESULTS: MHE time-to-fatigue performance declined by 15% at WI 3 (p = 0.009) and by 17% on WI 5 (p = 0.002). Performance continued to decline by 22% at 24-h post-WI (p < 0.001) and by 12% on 72-h post-WI (p = 0.019). Fifty-repetition IK knee extension total work decreased by 5% (p = 0.002) on WI 3, and was further reduced by 7.5 and 12.3% (p = 0.032) at pre-WI 5 and 24-h post-WI, respectively. However, the rate of fatigue was 8 (p = 0.033) and 30% (p = 0.017) lower at WI 3 and 24-h post-WI when compared to WI 1, respectively, demonstrating the muscles were still fatigued from the previous hyperoxic WIs. We detected no significant limitations in oxygen off-loading kinetics during the exercise or MOC measurements. CONCLUSION: Repeated, resting, long-duration hyperoxic WIs caused significant reductions to muscular endurance but not to indirect measures of oxygen kinetics in load bearing and non-load bearing muscles.

Effects of Resting, Consecutive, Long-Duration Water Immersions on Neuromuscular Endurance in Well-Trained Males.

Purpose: This study examined the effects of repeated long-duration water immersions (WI)s at 1.35 atmospheres absolute (ATA) on neuromuscular endurance performance. We hypothesized that, following 5 days of consecutive, resting, long-duration WIs, neuromuscular endurance performance would decrease. Methods: Fifteen well-trained, male subjects completed five consecutive 6-h resting WIs with 18-h surface intervals during the dive week while breathing compressed air at 1.35 ATA. Skeletal muscle endurance performance was assessed before and after each WI, and 24 and 72 h after the final WI. Muscular endurance assessments included 40% maximum handgrip endurance (MHE) and 50-repetition maximal isokinetic knee extensions. Near infrared spectroscopy was used to measure muscle oxidative capacity of the vastus lateralis and localized muscle tissue oxygenation of the vastus lateralis and flexor carpi radialis. Simultaneously, brachioradialis neuromuscular activation was measured by surface electromyography. Results: A 24.9% increase (p = 0.04) in the muscle oxidative capacity rate constant (k) occurred on WI 4 compared to baseline. No changes occurred in 40% MHE time to exhaustion or rate of fatigue or total work performed for the 50-repetition maximal isokinetic knee extension. The first quartile of deoxygenated hemoglobin concentration showed a 6 and 35% increase on WIs 3 and 5 (p = 0.026) with second quartile increases of 9 and 32% on WIs 3 and 5 (p = 0.049) during the 40% MHE testing when compared to WI 1. Conclusion: Our specific WI protocol resulted in no change to muscular endurance and oxygen kinetics in load bearing and non-load bearing muscles.

Contribution of central and peripheral adaptations to changes in maximal oxygen uptake following 4 weeks of sprint interval training.

The current study examined the contribution of central and peripheral adaptations to changes in maximal oxygen uptake (V̇O2max) following sprint interval training (SIT). Twenty-three males completed 4 weekly SIT sessions (8 × 20-s cycling bouts at ∼170% of work rate at V̇O2max, 10-s recovery) for 4 weeks. Following completion of training, the relationship between changes in V̇O2max and changes in central (cardiac output) and peripheral (arterial-mixed venous oxygen difference (a-vO2diff), muscle capillary density, oxidative capacity, fibre-type distribution) adaptations was determined in all participants using correlation analysis. Participants were then divided into tertiles on the basis of the magnitude of their individual V̇O2max responses, and differences in central and peripheral adaptations were examined in the top (HI; ∼10 mL·kg-1·min-1 increase in V̇O2max, p < 0.05) and bottom (LO; no change in V̇O2max, p > 0.05) tertiles (n = 8 each). Training had no impact on maximal cardiac output, and no differences were observed between the LO group and the HI group (p > 0.05). The a-vO2diff increased in the HI group only (p < 0.05) and correlated significantly (r = 0.71, p < 0.01) with changes in V̇O2max across all participants. Muscle capillary density (p < 0.02) and ß-hydroxyacyl-CoA dehydrogenase maximal activity (p < 0.05) increased in both groups, with no between-group differences (p > 0.05). Citrate synthase maximal activity (p < 0.01) and type IIA fibre composition (p < 0.05) increased in the LO group only. Collectively, although the heterogeneity in the observed V̇O2max response following 4 weeks of SIT appears to be attributable to individual differences in systemic vascular and/or muscular adaptations, the markers examined in the current study were unable to explain the divergent V̇O2max responses in the LO and HI groups.

Mild hyperbaric oxygen inhibits the growth-related decline in skeletal muscle oxidative capacity and prevents hyperglycemia in rats with type 2 diabetes mellitus.

BACKGROUND: Humans and animals with type 2 diabetes mellitus (T2DM) exhibit low skeletal muscle oxidative capacity and impaired glucose metabolism. The aim of the present study was to investigate the effects of exposure to mild hyperbaric oxygen on these changes in obese rats with T2DM. METHODS: Five-week-old non-diabetic Long-Evans Tokushima Otsuka (LETO) and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into normobaric (LETO-NB and OLETF-NB) and mild hyperbaric oxygen (LETO-MHO and OLETF-MHO) groups. The LETO-MHO and OLETF-MHO groups received 1266 hPa with 36% oxygen for 3 h daily for 22 weeks. RESULTS: Fasting and non-fasting blood glucose, HbA1c, and triglyceride levels were lower in the OLETF-MHO group than in the OLETF-NB group (P < 0.05). In the soleus muscle, peroxisome proliferator-activated receptor δ/ß (Pparδ/ß), Pparγ, and PPARγ coactivator-1α (Pgc-1α) mRNA levels were lower in the OLETF-NB group than in all other groups (P < 0.05), whereas myogenin (Myog) and myogenic factor 5 (Myf5) mRNA levels were higher in the OLETF-MHO group than in the LETO-NB and OLETF-NB groups (P < 0.05). The soleus muscles in the OLETF-NB group contained only low-oxidative Type I fibers, whereas those in all other groups contained high-oxidative Type IIA and Type IIC fibers in addition to Type I fibers. CONCLUSIONS: Exposure to mild hyperbaric oxygen inhibits the decline in skeletal muscle oxidative capacity and prevents the hyperglycemia associated with T2DM. Pgc-1α, Myog, and Myf5 mRNA levels appear to be closely associated with skeletal muscle oxidative capacity in rats with T2DM.

Unloading-induced atrophy and decreased oxidative capacity of the soleus muscle in rats are reversed by pre- and postconditioning with mild hyperbaric oxygen.

Our aim was to determine the effects of pre- and/or postconditioning with mild hyperbaric oxygen (1.25 atmospheric pressure, 36% oxygen for 3 h/day) on the properties of the soleus muscle that was atrophied by hindlimb suspension-induced unloading. Twelve groups of 8-week-old rats were housed under normobaric conditions (1 atmospheric pressure, 20.9% oxygen) or exposed to mild hyperbaric oxygen for 2 weeks. Ten groups then were housed under normobaric conditions for 2 weeks with their hindlimbs either unloaded via suspension or not unloaded. Six groups subsequently were either housed under normobaric conditions or exposed to mild hyperbaric oxygen for 2 weeks: the suspended groups were allowed to recover under reloaded conditions (unrestricted normal cage activity). Muscle weights, cross-sectional areas of all fiber types, oxidative capacity (muscle succinate dehydrogenase activity and fiber succinate dehydrogenase staining intensity) decreased, and a shift of fibers from type I to type IIA and type IIC was observed after hindlimb unloading. In addition, mRNA levels of peroxisome proliferator-activated receptor γ coactivator-1α decreased, whereas those of forkhead box-containing protein O1 increased after hindlimb unloading. Muscle atrophy and decreased oxidative capacity were unaffected by either pre- or postconditioning with mild hyperbaric oxygen. In contrast, these changes were followed by a return to nearly normal levels after 2 weeks of reloading when pre- and postconditioning were combined. Therefore, a combination of pre- and postconditioning with mild hyperbaric oxygen can be effective against the atrophy and decreased oxidative capacity of skeletal muscles associated with hindlimb unloading.