Journal of Applied Physiology

Understanding skeletal muscle adaptation is key to optimizing training and rehabilitation strategies, yet the causal links between training stimuli and muscle response remain unclear. This gap reflects the difficulty of observing multi-scale adaptations within the same muscle in vivo. Calf muscles, critical for propulsion and postural control, remain relatively under-studied, and long-term outcomes with intermediate stages of adaptation are rarely documented. We investigated temporal and regional remodelling of the gastrocnemius medialis muscle during 12 weeks of eccentric training in six young, healthy adults. Participants trained on alternate days with progressive overload calf raise exercises. Muscle architecture and function were assessed at baseline, 6, and 12 weeks using 3D ultrasonography and dynamometry. Group-level analysis revealed a 38% increase in peak plantarflexion torque at 90{degrees} (p < 0.01), while muscle volume, PCSA, fascicle length, and pennation angle showed no consistent changes. Individual response profiles varied: some participants showed longitudinal growth with longer fascicles and smaller pennation angles, others displayed radial growth with increased PCSA, while some exhibited minimal architectural change despite torque gains. Trends suggested shifts in fascicle length-angle torque relationships and altered tendon compliance in certain individuals. By combining regional muscle morphology with functional outcomes over time, this study demonstrates the feasibility of tracking multi-scale adaptation in vivo. The pronounced inter-individual and region-specific variability highlights the need for tailored interventions that consider baseline architecture and regional strain patterns to optimize outcomes in training and rehabilitation.

The short-term scaling exponent of detrended fluctuation analysis (DFA1) applied to interbeat intervals may provide a method to identify ventilatory thresholds and indicate systemic perturbation during prolonged exercise. The purposes of this study were to i) confirm whether DFA1 values of 0.75 and 0.5 coincide with the gas exchange threshold (GET) and respiratory compensation point (RCP), ii) quantify DFA1 during constant-speed running near the maximal lactate steady state (MLSS), and iii) assess the repeatability of DFA1 between MLSS trials. Seventeen runners performed an incremental running test, and eleven and ten runners also performed constant-speed running 5% below, at, and 5% above the MLSS, and a repeat trial at MLSS, respectively. GET (bias [LOA]: -3.6 [-9.1 to 1.9] mL{middle dot}kg-1{middle dot}min-1) and RCP (-3.5 [-14.1 to 7.2] mL{middle dot}kg-1{middle dot}min-1) were overestimated using DFA1. DFA1 responses during 30-min running trials near MLSS were variable (i.e., 0.27 to 1.24), and affected by intensity (p=0.019) and duration (p=0.001). No difference in DFA1 was detected between MLSS trials (p=0.926). These results question whether DFA1 values can accurately delineate exercise thresholds, but the dependency of DFA1 on intensity and duration support its potential use to quantify systemic perturbations imposed by continuous exercise.

Handgrip exercise (HGE) is a safe, accessible exercise modality shown to improve cardiovascular health and is particularly promising for individuals with limited mobility who cannot engage in traditional exercise. Given that contraction type and intensity influence systemic cardiorespiratory variables that affect cerebral blood flow regulation, this study examined the acute systemic hemodynamic and cerebrovascular responses to static and rhythmic HGE protocols at varying intensities. Thirty-three healthy young adults (17 males; 16 females age 22(1) years) performed four separate 5-minute HGE protocols in a randomized order: static HGE at 15% (S15) of maximal voluntary contraction (MVC), static HGE at 30% MVC, rhythmic HGE at 30% MVC, rhythmic HGE at 60% (R60) MVC. We hypothesized that rhythmic HGE at higher intensities would produce the greatest cerebrovascular responses due to enhanced venous return and cardiac output, while static HGE at higher intensities would elicit the greatest systemic (i.e., blood pressure, HR, ventilation) responses. Cerebral (middle cerebral artery blood velocity [MCAv] and cerebrovascular conductance index [MCACVCi], internal carotid artery [ICA] diameter, velocity, blood flow, and shear rate) and systemic hemodynamics (systolic [SBP], diastolic [DBP], mean arterial pressure [MAP], heart rate [HR], cardiac output [CO]), and end-tidal carbon dioxide (PETCO2) levels were averaged over the final 30s of each minute of exercise. There was a significant time and protocol interaction effect on HR (p<0.001). We found significant main effects of exercise protocol for MCAv (p<0.001), MCACVCi (p<0.001), ICA diameter (p=0.01) and blood flow (p=0.001), and PETCO2 (p=0.002). Greatest increases in MCAv alongside the largest reduction in ICA blood flow occurred in R60. The greatest increase in MCACVCi and ICA blood flow (from baseline) occurred in R30 compared to other protocols. In addition to the greater cerebrovascular responses, we also observed more modest systemic responses (lower HR, MAP, CO) and lower self-reported ratings of perceived exertion (p<0.001) in R30 compared to other protocols. Acute increases in MCACVCi and ICA blood flow observed in R30 (despite the lower perceived effort) may suggest that rhythmic HGE at low-moderate intensities can be a tolerable prescription for inducing exercise-related cerebrovascular adaptations (i.e., improved cerebral perfusion) in populations that may require adapted physical activity.

Ventilatory thresholds (VT1 and VT2) are critical in exercise prescription and athletic training, delineating the transitions from aerobic to anaerobic metabolism. More specifically, VT1 signifies the onset of lactate accumulation whilst VT2 signifies the onset of metabolic acidosis. Accurate determination of these thresholds is vital for optimizing training intensity. Fractal correlation properties of heart rate variability (HRV), particularly the short-term scaling exponent alpha 1 of Detrended Fluctuation Analysis (DFA-1), have demonstrated potential for this purpose. This study validates the accuracy of commercial ventilatory threshold estimation algorithm (VT-algorithm) developed by Kubios. The VT-algorithm employs instantaneous heart rate (HR) relative to HR reserve and respiratory rate (RF), along with the DFA-1. Sixty-four physically active participants underwent an incremental cardiopulmonary exercise test (CPET) with inter-beat interval (RR) measurements. DFA-1 and the Kubios VT-algorithm were used to assess HR and oxygen uptake (VO2) at ventilatory thresholds. On average VO2 at true VT, DFA-1, and VT-algorithm derived ventilatory thresholds were 1.74, 2.00 and 1.89 l/min (VT1) and 2.40, 2.41 and 2.40 l/min (VT2), respectively. Correspondingly, average HRs at the true VT, DFA-1, and VT-algorithm thresholds were 141, 151 and 142 bpm (VT1) and 169, 168 and 170 bpm (VT2), respectively. When compared to the true thresholds, Bland-Altman error statistics (bias {+/-} standard deviation of error) for the DFA-1 thresholds were -0.26{+/-}0.41 l/min or -10{+/-}16 bpm at VT1 and 0.00{+/-}0.34 l/min or 1{+/-}10 bpm at VT2, whereas the VT-algorithm errors were - 0.15{+/-}0.28 l/min or -1{+/-}11 bpm at VT1 and 0.01{+/-}0.20 l/min or -1{+/-}7 bpm at VT2. HRV based VT determination algorithms accurately estimate ventilatory thresholds, offering insights into training zones, internal loading, and metabolic transitions during exercise without the need of laboratory equipment. The Kubios VT-algorithm, which incorporates instantaneous HR and RF along with DFA-1, provided higher accuracy for VO2 and HR values for both VT1 and VT2.

It is unclear whether muscle functional adaptations to concentric (CON-RT) and eccentric (ECC-RT) resistance training are most specific to their exercise characteristics or the structural adaptations they evoke. In this study, the effects of effort- and volume-matched CON-RT and ECC-RT on regional hypertrophy, muscle architecture, and function were compared, and associations between the outcomes were explored. Twelve trained young men (25.5{+/-}3.6y) completed 18 isokinetic ankle-dorsiflexion exercise sessions over 6 weeks: CON-RT in one leg and ECC-RT in the other (2-4 sets, 6-10 maximal repetitions, 10{degrees}/s). Tibialis anterior size and architecture (ultrasound imaging) and maximum voluntary dorsiflexion function (isokinetic dynamometry) were assessed. Muscle thickness increased similarly between conditions and across proximal-distal regions (8%), pennation angle increased more in CON-RT (8%) than ECC-RT (4%), and fascicle length increased only after ECC-RT (7%). Functional adaptations were more closely associated with specific structural adaptations than with contraction mode, velocity, or angle. Isometric torque increased similarly in both conditions overall (8%) but CON-RT improved only at shorter muscle lengths and shifted the peak-torque angle leftward, whereas ECC-RT improved at both shorter and longer lengths and broadened the torque-angle plateau, which was associated with fascicle length increases. ECC-RT produced greater increases in both eccentric (13%) and concentric torques (17%) than CON-RT (3%, 9%, respectively), and changes were similar across velocities - contrary to the training specificity theory. Changes in pennation angle were associated with dynamic strength changes. These findings suggest that muscle function adapts to the structural changes induced by training, regardless of the training scheme used.

BackgroundEccentric exercise (ECC) is widely recognized as an effective treatment for non-insertional Achilles tendinopathy (NIAT); however, the mechanisms underlying its apparent superiority over concentric exercise (CON) remain poorly understood. This randomized controlled trial aimed to investigate changes in triceps surae motor unit firing properties, pain, function, and AT morpho-mechanical properties following a 6-week intervention involving torque feedback training with isolated ECC and CON contractions in individuals with NIAT. MethodsTwenty-six individuals with NIAT were randomized to ECC or CON training. Motor unit firing properties (mean discharge rate [MDR], recruitment and de-recruitment thresholds, and torque-firing cross-correlation and neuromechanical delay) were assessed in the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SO) muscles using high-density surface electromyography (HD-sEMG) during isometric plantarflexion at 10%, 40%, and 70% of maximal voluntary contraction (MVC). Pain, function (VISA-A), and tendon properties (ultrasound, elastography) were measured at baseline, week 3, and week 6. ResultsBoth groups showed similar improvements in pain (P < 0.0001) and VISA-A scores (P < 0.001). Tendon stiffness increased in both groups by week 3 but was higher in ECC by week 6 (P = 0.02). Motor unit adaptations differed: CON demonstrated an increase in MG MDR at 40% MVC, while ECC showed a decrease (interaction: P = 0.0008). Only ECC led to increased de-recruitment thresholds in the LG at 70% MVC (P < 0.0001). However, both groups exhibited reduced MDR in the LG at high-force levels (P < 0.05). Additionally, both interventions reduced GL torque-firing relationships (P = 0.025) and decreased SO neuromechanical delay (P = 0.031). ConclusionA 6-week visuo-motor torque feedback training program involving isolated CON or ECC contractions leads to comparable improvements in clinical outcomes. However, contraction-specific and muscle-specific changes in motor unit function and tendon stiffness suggest distinct neuromechanical adaptations. These differences may underlie the observed effects and warrant further investigation in longer-term studies to determine their impact on long-term clinical outcomes. HIGHLIGHTS- Changes in clinical outcomes, tendon morphomechanical properties, and triceps surae motor unit behavior were assessed for the first time following a 6-week rehabilitation protocol for non-insertional Achilles tendinopathy, involving isolated concentric (CON) or eccentric (ECC) contractions. - Both CON and ECC training led to comparable improvements in pain, self-reported outcomes, and perceived function. - Despite these similar clinical improvements, CON and ECC protocols produced distinct adaptations in estimated tendon stiffness and motor unit firing characteristics. These neuromechanical differences may indicate potential long-term divergences between training modalities, which should be explored in studies with extended intervention periods.

The contributions of intrinsic muscle fiber resistance during mechanical perturbations to standing and other postural behaviors are unclear. Muscle stiffness, a traditional metric for estimating muscles intrinsic resistance to stretch, is known to vary depending on the current level and history of the muscles activation, as well as the muscles recent movement history; this property has been referred to as history dependence or muscle thixotropy. However, we currently lack sufficient data about the degree to which muscle stiffness is modulated across posturally-relevant characteristics of muscle stretch and activation. Here, we characterized the history dependence of muscles resistance to stretch in single, permeabilized, activated, muscle fibers in posturally-relevant stretch conditions and activation levels. We used a classic paired muscle stretch paradigm, varying the amplitude of a "conditioning" triangular stretch-shorten cycle followed by a "test" ramp-and-hold imposed after a variable inter-stretch interval. We tested low (<15%), intermediate (15-50%) and high (>50%) muscle fiber activation levels, evaluating short-range stiffness and total impulse in the test stretch. Muscle fiber resistance to stretch remained high at conditioning amplitudes of <1% L0 and inter-stretch intervals of >1 s, characteristic of healthy standing postural sway. A ~70% attenuation of muscle resistance to stretch was reached at conditioning amplitudes of >3% L0 and inter-stretch intervals of <0.1s, characteristic of larger, faster postural sway in balance-impaired individuals. Overall, amplitude and inter-stretch interval interact to disrupt myofilaments such that intrinsic resistance to stretch is attenuated if the stretch is large enough and/or frequent enough. Summary StatementIntrinsic muscle fiber resistance to stretch is preserved after small, slow pre-movements based on healthy postural sway, but markedly reduced as pre-movements increase to emulate abnormal postural sway.

ObjectivesDeficits in muscle performance could be a consequence of a reduced ability of a motor neuron to increase the rate in which it discharges. This study aimed to investigate motor unit (MU) discharge properties of each Triceps surae muscle (TS), and TS torque steadiness during submaximal intensities in runners with Achilles tendinopathy (AT). MethodsWe recruited runners with (n=12) and without (n=13) mid-portion AT. MU discharge rate was analysed for each of the TS muscles, using High-Density surface electromyography during 10 and 20% isometric plantar flexor contractions. ResultsMU mean discharge rate was lower in the Gastrocnemius lateralis (GL) in AT compared to controls. In AT, GL MU mean discharge rate did not increase as torque increased from 10% peak torque, 8.24pps (95%CI: 7.08 to 9.41) to 20%, 8.52pps (7.41 to 9.63, p=0.540); however, in controls, MU discharge rate increased as torque increased from 10%, 8.39pps (7.25 to 9.53) to 20%, 10.07pps (8.89 to 11.25, p<0.001). There were no between-group difference in Gastrocnemius medialis (GM) or Soleus (SOL) MU discharge rates. We found no between-groups differences in coefficient of variation of MU discharge rate in any of the TS muscles nor in TS torque steadiness. ConclusionOur data demonstrates that runners with AT may have a reduced neural drive to GL, failing to increase MU discharge rate to adjust for the increase in torque demand. Further research is needed to understand how interventions focusing on increasing neural drive to GL would affect muscle function in runners with AT.

BackgroundPushing/pulling isometric muscle actions (PIMA) are commonly used to assess strength, fatigability, and neuromechanical function, whereas holding isometric muscle actions (HIMA), applied in rehabilitation and performance settings, remain less clearly defined and comparatively understudied. Evidence suggests that PIMA and HIMA may elicit distinct neural and cardiovascular responses, yet inconsistent operational definitions complicate interpretation and application. This review synthesized research directly comparing PIMA and HIMA to clarify their physiological profiles, identify research gaps and explore practical relevance. MethodsThe protocol was pre-registered with PROSPERO (CRD42024530386). Databases were searched for peer-reviewed studies comparing PIMA and HIMA. Study quality and risk-of-bias were evaluated, and meta-analyses and meta-regressions were performed on time-to-task-failure (TTF), ratings of perceived exertion (RPE), heart rate (HR), and mean arterial pressure (MAP). ResultsFifty-four studies (publication year 2012.9{+/-}6.9; 1995-2024) were identified (N=919 participants; [~]29.8{+/-}10.7 years). Thirty-five studies reported performance measures, 45 examined neural outputs, and 14 assessed cardiovascular or metabolic responses. Meta-analysis revealed longer TTF for PIMA vs. HIMA at the same absolute intensity (n=407; g=-0.74, p<0.001), except for two studies on axial muscles (g=1.78-3.59, p<0.001). Individual-study patterns suggest diminishing TTF differences at higher intensities; however, since two other studies found clear differences, this may reflect methodological heterogeneity rather than a true intensity effect. No significant differences were identified for HR, MAP, or RPE at relative time points, except for higher RPE at 50%TTF during PIMA. Qualitatively, PIMA was associated with higher peak torques and discharge rates, whereas HIMA was associated with higher burst rates, glucose uptake, and force fluctuation increases. ConclusionsThese mechanistic distinctions may hold practical relevance as PIMA may be beneficial for prolonged activation and agonist neuromuscular adaptations. In contrast, HIMA could provide diagnostic value, injury-prevention potential, and time-efficient muscular, neural, and cardiovascular adaptations in rehabilitation. Methods varied widely across studies, making additional meta-analyses impossible. Randomized controlled trials are required to confirm the use of PIMA vs HIMA in clinical or performance contexts. Key PointsO_LIPushing/pulling and holding isometric actions produce distinct neuromuscular and physiological responses and should not be considered equivalent. C_LIO_LIPushing/pulling actions generally support longer force maintenance, with task- and muscle-specific exceptions. C_LIO_LINeural, mechanical, and metabolic characteristics differ, with pushing/pulling emphasizing antagonist force output while holding is more neuromuscular complex and metabolically taxing. C_LIO_LIThese differences suggest divergent applications, with pushing/pulling suited to performance goals and holding suited to rehabilitation and specific diagnostic contexts. C_LI

Standing posture control critically depends on the activation of the soleus (SOL) and medial gastrocnemius (MG), which serve distinct functional roles. Identifying underlying neural mechanisms has been challenging, as conventional invasive techniques sample only limited motor units (MUs). Recent advances in high-density surface electromyography (HDsEMG) have enabled analysis of MU activity and estimation of common synaptic inputs to spinal motoneurons. Therefore, we aimed to elucidate the common synaptic inputs underlying the distinct MU behaviors of SOL and MG during standing. We recorded HDsEMG from the SOL and MG, alongside electroencephalography, from 20 male participants during standing and isometric voluntary contractions. EMG signals were decomposed into individual MU activity, with common synaptic inputs estimated through intramuscular and corticomuscular coherence analyses (IMC and CMC). Compared to SOL, the MG exhibited significantly higher delta-, alpha-, and beta-band IMC during standing. In task comparisons, alpha-band IMC increased during standing specifically in the MG. Furthermore, although beta-band CMC decreased in both muscles while standing, IMC was preserved in the MG but markedly reduced in SOL. This dissociation suggests that the common neural drive to the MG during standing is likely derived from subcortical rather than cortical pathways. These results demonstrate that the SOL and MG are governed by distinct neural control strategies, which likely underlie their functional roles. Given the low CMC, the MG relies on strong common synaptic input from subcortical pathways (e.g., vestibulospinal and reticulospinal) to produce rapid corrective torque, whereas the SOL functions with lower neural synchrony to ensure steady ankle stiffness. Key pointsO_LIThe soleus and medial gastrocnemius play distinct roles in standing control, however, due to technical limitations, it has been difficult to identify the underlying neural mechanisms responsible for these differences. C_LIO_LIUsing high-density surface electromyography, we examined motor unit activity and neural inputs to these muscles during standing. C_LIO_LIThe medial gastrocnemius shows greater common synaptic input, potentially facilitating rapid ankle plantarflexion torque generation to correct postural sway. C_LIO_LIThe soleus exhibits lower motor unit synchrony, enabling stable and continuous ankle plantarflexion torque generation for body weight support. C_LIO_LIThis study demonstrates that the soleus and medial gastrocnemius are governed by distinct neural control strategies, which likely underlie their distinct functional roles. C_LI Abstract figure legend O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/698550v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@be53aorg.highwire.dtl.DTLVardef@f6793aorg.highwire.dtl.DTLVardef@190e8f9org.highwire.dtl.DTLVardef@af5e4b_HPS_FORMAT_FIGEXP M_FIG C_FIG Motor unit spike trains were decomposed from high-density surface electromyograms recorded from the medial gastrocnemius (MG; left; red) muscle and soleus (SOL; right; blue). To compare the neural input to the spinal motor neurons between them, we quantified the intramuscular coherence (IMC) of motor unit spike trains within the delta, alpha, and beta bands. MG exhibited greater IMC than SOL during standing, indicating stronger common synaptic input, likely mediated by vestibulospinal and reticulospinal pathways. In contrast, SOL showed lower IMC, suggesting a greater contribution of independent synaptic input. As a consequence, high motor-unit synchrony in the MG supports rapid, phasic torque generation for postural sway attenuation, whereas low synchrony in the SOL enables smooth, steady torque production for weight bearing during standing.

Hyperbaric oxygen (HBO), physical exercise, and eicosapentaenoic acid (EPA) intake combined may have beneficial effects on blood components and vascular endothelial function. To test this hypothesis, we conducted a randomized crossover trial involving healthy adult male participants. Participants were assigned to three groups: two performed exercise under HBO or normobaric normoxia (NN) conditions while taking EPA (HBO + Ex + EPA and NN + Ex + EPA), and one received EPA without exercise (EPA control). Each exercise-based intervention lasted for 4 weeks, with a 1-week washout period before crossover into the other environment. Blood parameters and endothelial function were measured before and after the interventions. In the HBO + Ex + EPA group, hemoglobin (Hb) levels remained unchanged despite reductions in the red blood cell (RBC) count and hematocrit (Ht). No significant changes were observed in the RBC or Ht in the NN + Ex + EPA or EPA control groups, suggesting that the reductions were likely attributable to exercise performed under HBO conditions. No significant changes were observed in other blood parameters (blood sugar, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl transpeptidase concentrations), blood lipid concentrations (triglycerides and high- and low-density lipoprotein cholesterol), or indicators of vascular endothelial function (baseline brachial artery diameter, maximum brachial artery diameter, flow-mediated dilation percentage, and vascular wall shear rate) in either of the exercise groups. In the EPA control group, triglyceride levels significantly decreased and high-density lipoprotein cholesterol levels increased, whereas no significant changes were observed in other blood markers or indicators of vascular endothelial function. In the current study, Hb levels were maintained despite reductions in the RBC count and Ht during exercise under HBO conditions. This study provides valuable fundamental insights into the effects of exercise performed in extreme physiological environments, such as HBO conditions, on blood homeostasis and vascular function.

We employed interleaved dynamic 1H magnetic resonance imaging (MRI) and 31P MR spectroscopy in combination with arm-cycling to investigate correlations of exercise hyperemia and muscle energetics in the triceps brachii (TB) muscle of the upper arm of healthy individuals. The parameter hyperemic slope (HS) determined from MRI acquisitions immediately after exercise was used as primary index of maximal TB oxygenation level in response to exercise. We found that HS tended to be inversely correlated with TB acidification during exercise (P =0.06) as opposed to findings in leg muscle. The absolute increase in cardiac-output during exercise was found to be uncorrelated with HS (P =0.19) suggesting that the magnitude of the hyperemic response to exercise involving a minor muscle mass is governed by local rather than systemic factors. Post-exercise, the rate of metabolic recovery was fastest in the study subject with highest HS and slowest for the opposite case, although this correlation failed to reach significance in our small study cohort (P =0.14). This finding fits the conclusion of previous musculoskeletal 31P MRS studies that oxygen supply to working skeletal muscle exerts significant metabolic control over oxidative muscular energy balance even if the physical task only involves a minor muscle mass. New & NoteworthyThe use of interleaved dynamic 1H magnetic resonance imaging (MRI) and 31P MR spectroscopy uniquely afforded simultaneous interrogation of exercise hyperemia and muscle energetics in the human upper-arm. We found triceps muscle acidification during arm-cycling and readouts of hyperemia were, if anything, inversely correlated. Macrovascular and microvascular readouts of hyperemic response were uncorrelated. Post-exercise metabolic recovery rate tended to correlate with exercise hyperemia.

The ability to withstand impairments in key physiological variables during prolonged exercise, known as durability, is emerging as an important factor in cycling performance. While females possess physiological characteristics that could confer enhanced durability relative to males, little is known about potential sex differences. 32 trained cyclists (16 males and 16 females) performed an incremental exercise test to exhaustion in visit 1. In visit 2 they performed 90 minutes of heavy intensity cycling (HVY) at 110% of gas exchange threshold (GET), followed by another incremental test. During HVY, pulmonary gas exchange ([V]O2 and [V]CO2) ventilation ([V]E), heart rate (HR), rating of perceived exertion (RPE), near-infrared spectroscopy and electromyography were recorded, and blood lactate (BLa) was collected. Before and after HVY, maximal voluntary contraction (MVIC), voluntary activation (VA) and potentiated twitches (100Hz, 10Hz, Qtw{middle dot}pot) of the knee extensors were assessed. Power at GET (-16{+/-}15% vs -2{+/-}13%) and respiratory compensation point (-13{+/-}10% vs -6{+/-}9%) decreased more in males than females (P[&le;]0.049). All aspects of neuromuscular function decreased from pre to post (all P<0.001), without sex differences (P[&ge;]0.096). During HVY, HR, [V]O2 (%peak), relative energy expenditure increased more in males (P[&le;]0.008), whereas respiratory exchange ratio decreased more in females (P=0.001). BLa was higher in males than females (P=0.030). Muscle oxygen extraction was lower (P=0.004) and tissue saturation index higher for females (P<0.001). The smaller reductions exhibited by females in submaximal thresholds, associated with lesser derangements to oxidative efficiency, highlight the need to consider sex-specific training prescription and pacing strategies for long duration events. Key PointsO_LIDurability, as measured by the reduction in incremental exercise test outcomes, is relatively unexplored in females compared to males, despite physiological sex differences that might confer a female advantage. C_LIO_LIAfter 90 minutes of heavy intensity cycling, males demonstrated greater reductions in the power outputs associated with gas exchange threshold and respiratory compensation point. C_LIO_LIThe maximal rate of oxygen consumption and incremental test peak power output decreased similarly in both sexes. C_LIO_LIThese changes are associated with greater carbohydrate metabolism and losses of efficiency in males, whereas no sex differences were observed in neuromuscular fatigue. C_LI

The metabolic and physiological responses to exercise vary markedly across different levels of fitness and training status. While maximal oxygen uptake (VO2max) has historically been used as the primary indicator of cardiorespiratory fitness, increasing attention has been directed toward metabolic and bioenergetic responses to exercise, including blood lactate concentration and substrate utilization. In this study, we examined comprehensive physiological and metabolic responses during graded exercise testing in 204 male cyclists spanning four fitness categories: Tour de France professional cyclists, competitive cyclists, master cyclists, and recreational cyclists. Measurements included power output, VO2, blood lactate concentration, and rates of fat and carbohydrate oxidation derived from indirect calorimetry. Across all exercise intensities, performance and metabolic parameters followed a clear hierarchical pattern corresponding to competitive level. Tour de France cyclists demonstrated significantly greater power output, higher VO2max, lower blood lactate concentrations at matched workloads, higher fat oxidation rates, and delayed reliance on carbohydrate oxidation compared with less-trained groups. Strong inverse correlations were observed between blood lactate concentration and fat oxidation, while positive correlations were observed between blood lactate concentration and carbohydrate oxidation across all fitness levels.

Non-insertional Achilles tendinopathy (NIAT) induces morpho-mechanical changes to the Achilles tendon (AT). However, evidence on how triceps surae motor unit firing properties are influenced by altered tendon mechanics in NIAT is limited. This study investigated motor unit firing properties (mean discharge rate (DR), recruitment and de-recruitment thresholds, and discharge rate variability (COVisi)), motor unit firing-torque relationships (cross-correlation coefficient between cumulative spike train (CST) and torque, and neuromechanical delay), and neural drive distribution (connectivity strength and functional networks) of the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (SO) muscles during isometric plantarflexion contractions at 10%, 40%, and 70% maximal voluntary contraction (MVC) using high-density surface electromyography on 26 individuals with NIAT and 25 healthy controls. Furthermore, ATs morpho-mechanical properties (thickness, cross-sectional area, length and stiffness) were assessed via ultrasound imaging. NIAT individuals showed reduced tendon stiffness and increased thickness (p<0.01). Motor unit properties changed in a load and muscle-dependent manner. LG DR increased (p=0.002) and de-recruitment threshold decreased (p=0.039) at 70%MVC in the NIAT group compared to controls. The CST-torque cross-correlation coefficient of the LG decreased at 10%MVC (p<0.0001) and increased at 70%MVC (p=0.013) in the NIAT group. Connectivity strength for the 0-5 Hz and 5-15 Hz frequency bands decreased (p<0.01) in the NIAT group at 10%MVC. This study shows that individuals with NIAT exhibit load-dependent changes in motor unit firing properties, motor unit-torque relationships, and neural drive distribution to the triceps surae. These alterations may be due to muscle-specific compensations for the modified mechanical properties of the AT. KEY POINTS- Individuals with non-insertional Achilles tendinopathy (NIAT) have changes of the neural drive to the lateral gastrocnemius (LG) muscle and altered contribution of the LG to the net plantarflexion torque. - Individuals with NIAT show a more uneven distribution of neural drive to the triceps surae muscle at low force levels, characterized by reduced intermuscular coherence between the medial and lateral gastrocnemius in the 0-5 Hz and 5-15 Hz bands compared to the control group. - Our findings support the idea that the LG may have a central role in the pathophysiology of this condition, possibly affecting the load transmission to the Achilles tendon (AT).

Autonomic nervous system (ANS) activity causes acute variations in the blood pressure. Blood pressure responds to high intensity interval exercise (HIIE) repeatedly during alternating intensities, however, ANS response to the changing intensities of HIIE is unknown. We characterized the response of beat-to-beat blood pressure variability (BTB BPV) to an acute bout of HIIE using coefficient of variation (CoV) and spectral low frequency [LF], and high frequency [HF] domains. Our hypotheses were mean arterial pressure BTB BPV, would increase during 1) high intensity and 2) active recovery of HIIE compared to baseline (BL). BTB BPV would reduce during 1) cool down 2) post HIIE 3) 30 minutes post HIIE compared to BL in young adults. HIIE included bouts of 1-minute high-intensity separated by 1-minute recovery ({square}70% and 10% estimated Wattmax) for total of 10 minutes on a recumbent stepper. A secondary analysis was performed using twenty-one datasets of young individuals (age 25{+/-}1.5, 48% female). During high intensity, LF and HF increased compared to BL (p < 0.05) indicating increased sympathetic activity and breathing. During active recovery, LF and HF remained elevated above BL and were greater than during high intensity (p [&le;] 0.02). Sympathetic activity reduced back to BL immediately post HIIE but returned to being higher than BL at 30 minutes after HIIE (p=0.001). BTB BPV CoV also increased during HIIE compared to BL (p<0.05). Results suggest that young healthy individuals have increased BTB BPV during HIIE suggesting cardiovascular system responds to ANS fluctuations during changing exercise intensity. New and NoteworthyThis novel study analyzed beat -to-beat blood pressure variability during high intensity interval exercise (HIIE) in young healthy adults. We found that blood pressure variability was highest during active recovery compared to resting or high intensity exercise. Moreover, variability increased during HIIE but returned to resting post-exercise. These findings provide valuable insights into the blood pressure and ANS responses to HIIE, contributing to our understanding of their impact on overall cardiovascular health in young adults.

BackgroundThis study investigated whether nocturnal oxygen therapy (NOT) improves next-day cerebrovascular function in lowlanders with COPD staying at moderate altitude. MethodsThis randomized, placebo-controlled crossover trial was performed in stable patients with moderate to severe COPD (FEV1/FVC <0.7 and FEV1 30-80%predicted), living <800m and pulse oximetry (SpO2) [&ge;]92%. Patients underwent assessments at 490m and during 2 stays of 2 days at 2048m while NOT or placebo (each at 3L min-1 through nasal cannula) were applied according to a randomized cross-over design. At both altitudes, SpO2, cerebral tissue oxygenation (CTO, near-infrared spectroscopy), mean arterial blood pressure (MAP, finger plethysmography) and middle cerebral artery systolic peak blood flow velocity (sMCAv, transcranial Doppler ultrasound) were assessed while patients were (0) quietly breathing FiO2 0.21; (i) quietly breathing FiO2 1.0, (ii) voluntarily hyperventilating, (iii) voluntarily hyperventilating under FiO2 1.0, and (iv) during head-up tilting. Indices of cerebrovascular responsiveness to changes in blood gases and blood pressure were computed. ResultsA total of 18 patients (8 women aged mean{+/-}SD 65{+/-}5y, FEV1 54.7{+/-}13.9%predicted) were analyzed. At 2048m under placebo, patients became hypoxemic, mean{+/-}SE SpO2 90.3{+/-}0.4% vs. 93.7{+/-}0.4% at 490m, while MAP, CTO and sMCAv remained unchanged compared to 490m. All ventilatory maneuvers at 2048 m induced greater increases in SpO2 compared to 490m while changes in MAP, CTO and sMCAv were similar. Head-up tilting induced a similar blood pressure fall at 2048m compared to 490m, whereas cerebral blood flow velocity changed less in response to systemic hypotension (mean{+/-}SE {Delta}sMCAv/{Delta}MAP 0.9{+/-}0.3 vs. 2.3{+/-}0.4cm s-1 mmHg-1) at 2048m. No alteration in cerebrovascular function as a treatment effect of NOT was observed in either maneuver. ConclusionThis randomized clinical trial in moderate-to-severe COPD patients ascending to 2048m showed that moderate daytime systemic hypoxemia does not translate to cerebral hypoxia nor cerebrovascular autoregulatory impairments while at rest or under ventilatory or orthostatic challenges.

BackgroundThe cardiovascular (CV) benefit of CPAP in OSA remains debated and its effects on new OSA-related CV risk markers are unclear. We aimed to quantify short-term CPAP effects on these markers along with vascular and autonomic phenotypes. MethodsIn a 2-week withdrawal study, patients on long-standing effective CPAP took part in three visits (V1-V3: on/off/back-on CPAP) with overnight polygraphy followed by vascular and autonomic phenotyping. Co-primary endpoints included endothelial function assessed by flow-mediated dilation (FMD) and baroreflex sensitivity (BRS), hypoxic burden (HB), pulse wave amplitude drop index (PWADi) and spontaneous-PWADi (excl. apnoea-triggered drops), and event-related heart-rate response ({Delta}HR). Between-visit differences were tested in adjusted mixed models, with visit or within-participant changes in AHI/HB as fixed effects. ResultsIn 42 participants (61{+/-}10 years, 83% male), CPAP withdrawal reinstated OSA (medians [IQR] V1 to V3: AHI 3.9[1.5, 8.8] to 33.4[19.5, 42.1] to 4.0[2.0, 8.8] events/h, HB 4.3[1.1, 8.7] to 51.3[19.7, 83.7] to 2.0[1.2, 6.5] %{middle dot}min/h, p<0.001) and increased total PWADi (mean{+/-}SD 42.25{+/-}18.73 to 50.22{+/-}17.77 to 41.29{+/-}17.14 drops/h, p<0.001), while spontaneous PWADi decreased as respiratory-events recurred (-1.17 drops/h per 10 events/h, p=0.015) along with FMD (3.7{+/-}1.9% to 3.2{+/-}2.5% to 4.2{+/-}2.7%, V2 vs V3 p=0.047). {Delta}HR and BRS were stable across visits. ConclusionShort-term CPAP re-initiation improved endothelial function (FMD), with no significant effects on autonomic measures (BRS, {Delta}HR) or structural vascular indices. This supports a temporal dissociation between rapidly reversible exposure metrics (AHI, HB) and slower dynamics of autonomic markers. Changes in spontaneous PWADi suggests that it may track physiological CPAP benefits beyond indices driven primarily by respiratory-event frequency.

BackgroundCalf muscle pump (CMP) failure is associated with the development and progression of chronic venous insufficiency as characterized by ambulatory venous hypertension (AVH). However, the explicit interconnection between AVH with CMP failure remains uncertain because the concept of CMP function is controversial. The study aimed to measure pressure in different segments of the great saphenous vein (GSV) and intramuscular vein of the gastrocnemius (GCM) during exercise. MethodsTwelve legs of nine healthy volunteers were enrolled in the study. Continuous pressure (IVCALF, GSV at ankle, proximal calf, and mid-distal thigh) and electromyography data (GCM and anterior tibial muscle [ATM]) were recorded during treadmill walking, running, and plantar flexion exercises. The pressure gradient (PG, mmHg) between adjacent points of measurement was calculated. Minute unit power of muscle pump ejection and suction ([Formula], and [Formula], MPa/min) were calculated and compared with the arterial blood supply of the lower extremity (LBF, L/min). ResultsPG demonstrated a consistent pattern of changes during walking and running. An absence of PG directed from the calf to the thigh (centripetal) in the GSV was observed. Instead, a retrograde PG was verified throughout the entire stride cycle. Its value decreased with the increase in stride cycle frequency. The dynamics of PG between the IV and GSV were the following: It was directed from the IV to GSV during GCM contraction and was reversed during ATM contraction and GCM relaxation (swing phase). LBF, [Formula], and [Formula] demonstrated similar exponential growth with the increase in stride frequency during walking and running. ConclusionsThe pressure gradient in the GSV prevents centripetal flow during locomotion. Instead, PG directs blood flow from the GSV toward intramuscular veins. The increase in CMP unit power was tightly coupled with lower extremity arterial blood supply growth that prevented ambulatory venous pressure rise during exercise. Novelty and Significance What Is Known?O_LIThe existence of a pressure gradient in superficial veins directed centripetally (from calf to thigh level) has been confirmed for the state of rest only (lying and standing). C_LIO_LIThe existence of a pressure gradient directed from intramuscular to superficial veins or vice versa has been confirmed for the artificial exercise tests only (tiptoe movements, walking in place etc.). C_LIO_LIThe main calf muscle pump function was considered as its ability to eject blood centripetally by posterior calf muscle group contraction. C_LI What New Information Does This Article Contribute?O_LIAn absence of pressure gradient directed from the calf to the thigh (centripetal) in the great the saphenous vein during locomotion. C_LIO_LIDuring locomotion, at the lower leg level, the primary route of blood outflow from the superficial veinous network toward intramuscular veins is a horizontal route (through perforating veins). C_LIO_LINew parameters are introduced to assess calf muscle pump effectiveness as its ability to maintain accordance between the muscle pump output and arterial blood supply during locomotion. C_LI The calf muscle pump (CMP) is known as a significant contributor to venous blood outflow from the lower extremity due to its ability to effectively eject blood in a centripetal direction. Therefore, CMP failure refers to an impaired ejecting ability associated with chronic venous insufficiency (CVI) occurrence and progression. It is expressed in the increase in ambulatory venous pressure referred to as ambulatory venous hypertension (AVH). However, multiple studies demonstrated a lack of agreement between defined CMP failure and AVH, the severity of CVI, and quality of life. Here we show that during locomotion, the CMP acts as a stream diversion pump redirecting blood flow from superficial veins (SVs) to intramuscular veins (IVs) through perforating veins. This is because the observed pressure gradient prevents centripetal blood flow from the calf to thigh level in the SVs and favors blood flow from SVs to IVs during the swing phase of the stride cycle. This function is provided by the synergetic work of antagonist calf muscles (anterior tibial muscle and gastrocnemius). Thereby, the CMP prevents pressure growth in the superficial veins of the lower leg (AVH) during exercise when the arterial blood supply increases according to exercise intensity.

BackgroundAerobic training enhances VO2max, yet the contribution of peripheral microvascular remodeling to this improvement remains insufficiently understood. This research demonstrates how two distinct training modalities, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT), influence oxygen transport dynamics and microvascular remodeling. MethodsTwenty-five healthy sedentary adults (15 women, 10 men; mean age 25 {+/-} 2 years; normal BMI) were randomly assigned to HIIT or MICT for 8 weeks. VO2max was assessed before and after the training program. 15 participants underwent non-invasive maximal cardiac output measurement (Qmax), while vastus lateralis muscle biopsies were obtained from 10 participants. Tissue samples were cleared and immunolabeled for VE-cadherin and alpha-smooth muscle actin to observe microvasculature architecture. A computational hemodynamic model integrating cardiac output and microvascular parameters was constructed to estimate flow dynamics. ResultsVO2max increased significantly in both training groups, with a greater improvement in HIIT (p = 0.024). Qmax increased similarly in both groups (p = 0.001), while calculated arteriovenous oxygen difference (a-vO2 diff) showed a trend toward improvement only in HIIT. No formation of new capillaries nor anastomoses (angiogenesis) was detected in either group; however, both HIIT and MICT induced significant capillary and venule dilation. Notably, only HIIT led to a significant increase in pericyte coverage (p = 0.047). Venules of both groups exhibited dilation accompanied by increased surrounding smooth muscle cells. No remodeling was found in arterioles. Hemodynamic modelisation estimated higher shear stress during HIIT than MICT and vasodilation tended to decrease shear stress over time during both training. Furthermore, pericyte recruitment was modelized to adapt to shear stress level limiting excessive capillary dilation during high effort intensity. ConclusionHIIT induces superior improvements in VO2max and distinct microvascular structural adaptations rather than angiogenesis. HIIT is supposed to stimulate a protective adaptation at the capillary level, limiting excessive dilation during maximal effort. Our hemodynamic model supports this shear stress-dependent mechanism. These findings underscore the role of exercise intensity and hemodynamics in shaping microvascular responses to endurance training. Clinical PerspectiveO_LIPeripheral adaptation to exercise is linked with the dilation of muscle capillaries and venules. C_LIO_LIMechanoadaptive responses, rather than growth factor-mediated angiogenesis, drive the remodeling of the muscle microvasculature. C_LIO_LIHigh-intensity interval training elicits higher shear stress than moderate continuous interval training, linking the adaptation of the microvasculature to increased blood flow as the primary factor that explains the superiority of HIIT compared to MICT in improving maximal oxygen consumption. C_LI Clinical implicationO_LITraining regimens should focus on increasing peripheral flow and shear stress to initiate microvasculature remodeling. C_LIO_LIPotentiating mechanoadaptative responses and microcirculation remodeling would provide a means to improve cardiovascular function and fitness C_LI