Journal of Applied Physiology

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.

RationaleMechanical ventilation rapidly induces slow and fast fiber contractile dysfunction in the human diaphragm, which could be attenuated by phrenic nerve stimulation. Here, we present data from a controlled trial of intraoperative phrenic stimulation to offset slow and fast fiber contractile dysfunction and myofilament protein derangements. ObjectivesIn this study, we tested the hypothesis that intraoperative hemidiaphragm stimulation would mitigate slow and fast fiber loss of contractile function in the human diaphragm. MethodsNineteen adults (9 females, age 59 {+/-}12 years) consented to participate. Unilateral phrenic twitch stimulation was applied for one minute, every 30 minutes during cardiothoracic surgery. Thirty minutes following the last stimulation bout, biopsies were obtained from the hemidiaphragms for single fiber force mechanics and quantitation of thin filament protein abundance. Effects of stimulation and fiber type on force mechanics were evaluated with linear mixed models with the subject treated as a random intercept effect. Measurements and Main ResultsSubjects underwent 6 {+/-}2 hemidiaphragm stimulations at 17 {+/-}6 mA, during 278 {+/-}68 minutes of mechanical ventilation. In slow-twitch fibers, cross-sectional area (p<0.0001) and specific force (p<0.0005) were significantly greater on the stimulated side. Longer-duration surgeries were associated with lower slow-twitch specific force (p<0.001). Stimulation did not alter contractile function of fast-twitch fibers or calcium-sensitivity in either fiber type. There were no differences in abundance or phosphorylation of myofilament proteins. ConclusionUnilateral phrenic stimulation during open chest surgery preserved contractile function of slow-twitch diaphragm fibers, but had no effect on relative abundance of sarcomeric proteins.

Intense unilateral muscle contractions evoke measurable activity within the contralateral neuroaxis, which can be detected with surface electromyographic activity in the resting homologous muscle. Physiological mirror activity (PMA), the unintentional increase in contralateral muscle excitation, has been implicated in cross-limb interactions and adaptations. Despite longstanding observations of PMA, it remains unknown whether this low-level muscle excitation influences local muscle metabolism. We addressed this question using a vascular occlusion test in 10 healthy adults. Surface electromyography and near-infrared spectroscopy-derived measures of tissue oxygen saturation and muscle oxygen consumption (mVO2) were obtained from the resting left forearm during vascular occlusion at rest and during fatiguing unimanual contractions of the right hand. PMA in the contralateral resting arm was greater during unimanual fatigue than during rest (mean difference: 8.9%AA, 95% CI: 4.1 to 13.8; p = 0.002, g = 1.20). This increase was accompanied by a steeper rate of tissue oxygen desaturation (mean difference: -0.132 %{middle dot}s-1, 95% CI: -0.227 to -0.037; p = 0.012, g = -0.91) and greater mVO2 (mean difference: 0.188 mL O2{middle dot}min-1{middle dot}100 g-1, 95% CI: 0.057 to 0.320; p = 0.010, g = 0.94). Greater PMA was associated with both a faster rate of oxygen desaturation (r = -0.85, 95% CI: -0.96 to -0.46, p = 0.002) and greater mVO2 (r = 0.78, 95% CI: 0.28 to 0.94, p = 0.008). These findings suggest that PMA is accompanied by increased local metabolic demand, consistent with a coupling between unintentional muscle excitation and oxygen extraction in the resting limb.

Older adults have difficulty maintaining balance when faced with postural disturbances, a task that is influenced by the stiffness of the triceps surae and Achilles tendon. Age-related changes in Achilles tendon stiffness have been reported at matched levels of effort, but measures typically have not been made at matched loads, which is important due to age-dependent changes in strength. Moreover, age-dependent changes in muscle stiffness have yet to be tested. Here, we investigate how age alters muscle and tendon stiffness and their influence on ankle stiffness. We hypothesized that age-related changes in muscle and tendon contribute to reduced ankle stiffness in older adults and evaluated this hypothesis when either load or effort were matched. We used B-mode ultrasound with joint-level perturbations to quantify ankle, muscle, and tendon stiffness across a range of loads and efforts in seventeen healthy younger and older adults. At matched loads, there was no significant difference in ankle, muscle, or tendon stiffness between groups (all p>0.13). However, at matched effort, older adults exhibited a significant decrease in ankle (27%; p=0.008), muscle (37%; p=0.02), and tendon stiffness (22%; p=0.03) at 30% of maximum effort. This is consistent with our finding that older adults were 36% weaker than younger adults in plantarflexion (p=0.004). Together these results indicate that, at the loads tested in this study, there are no age-dependent changes in the mechanical properties of muscle or tendon, only differences in strength that result in altered ankle, muscle, and tendon stiffness at matched levels of effort. NO_SCPLOWEWC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWANDC_SCPLOW NO_SCPLOWOTEWORTHYC_SCPLOWWe provide the first simultaneous estimates of ankle, muscle, and tendon stiffness in younger and older adults. In contrast to earlier conclusions, we found that muscle and tendon mechanical properties are unaffected by age when compared at matched loads. However, due to age-related decreases in strength, mechanical properties do differ at matched efforts. As such, it is important to assess the relevance of the comparisons being made relative to the functional tasks under consideration.

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.

Skeletal muscle function is central to the preservation of functional mobility. Given global shifts to an increasingly aged population, it is paramount that researchers and clinicians better understand the effectors of age-related functional decline. Muscle fatiguability acutely modifies skeletal muscle mechanics in ways that may affect joint stability. We have previously reported sex-specific reductions in cellular passive stress and modulus with fatigue in young males, but not females. Here, we assess whether older adults, who are more susceptible to fatigue during dynamic contractions, exhibit changes to cellular passive mechanics following fatiguing exercise. Muscle tissue biopsies were collected from 11 young and 11 older adults to measure passive stress and Youngs Modulus at the single fiber and bundle level. Biopsy samples were acquired from rested muscle and immediately following intermittent maximal contractions to task failure. Fatigue was associated with persistent reduction in elastic modulus that was specific to male participants, regardless of age. In muscle fiber bundles, containing both myofibrillar proteins and the extracellular matrix, fatigue-induced changes in modulus were largely negated, with the only significant change observed in young females, who demonstrated enhanced modulus with fatigue. Taken together our findings suggest a preservation of sex-based differences in the acute response to fatigue across the adult lifespan when measured at the myofilament level. However, further research is needed to understand how and whether these findings translate to the whole tissue level. New and noteworthyAcute modifications to muscle tissue mechanics are poorly understood but may have important impacts on functional outcomes in at-risk populations. Our findings suggest myocellular mechanics respond to acute fatigue stress in a sex specific manner that persists across the lifespan.

Abstract Purpose: MyotonPRO (MTP) and time-harmonic elastography (THE) are increasingly used to assess muscle mechanical properties, yet they operate on fundamentally different physical principles. MTP measures composite MTP stiffness (N/m) through surface oscillations, while THE quantifies intrinsic shear modulus (THE stiffness, kPa) via propagating shear waves. This study aimed at systematically compare MTP and THE measurements in the vastus lateralis muscle across different contraction intensities and examine how the skin layer and subcutaneous fat (SLSF) thickness influence their relationship. Methods: Twenty-six healthy adults (15 males, 11 females; age 25 [SD 4] years) underwent MTP and THE measurements of the vastus lateralis at rest and during isometric contractions at 15% and 30% maximal voluntary contraction (MVC). Effects of contraction intensities on tissue properties were assessed using univariate analyses of variance with repeated measures. Associations between the different outcomes of THE and MTP technologies were explored using Pearson's correlations and partial correlation coefficients separately for each contraction intensity with adjustment of the SLSF thickness of participants. Results: Both technologies detected contraction intensity-dependent stiffening across all outcomes (p < 0.001). THE stiffness increased from 5.3 [1.2] kPa at rest to 15.6 [6.1] kPa at 30% MVC; THE wave attenuation increased from 0.83 [0.19] to 1.42 [0.36] s/m while MTP stiffness increased from 337.3 [49.3] N/m at rest to 529.4 [160.7] N/m at 30% MVC. Correlations between modalities were weak and condition-dependent. THE wave attenuation did not significantly correlate with any MTP outcome across conditions. Conclusion: MTP and THE detect contraction-induced stiffening through fundamentally different physical mechanisms and should not be regarded as interchangeable. Their correlation is modest at rest and breaks down (or reverses) during active contraction, with subcutaneous fat as a key modifying factor. Clinical trial number: Not applicable.

BackgroundSarcopenia is associated with impaired physical function. Dual-task conditions, which increase cognitive demand during motor performance, may reveal deficits in neuromuscular control that are not evident during isolated motor tasks. Therefore, we investigated whether older adults with sarcopenia exhibit poorer steadiness of force and neural control (i.e., greater motor unit discharge variability, and altered common synaptic input) during submaximal contractions performed under single- and dual-task conditions compared with non-sarcopenic controls and master athletes. MethodsFifty-two older adults were included (74.3{+/-}7.3 years; 50% female). Sarcopenia was defined using Sarcopenia Definitions and Outcomes Consortium criteria based on low grip strength and slow gait speed. Participants (11 with sarcopenia, 22 controls, and 19 masters athletes) performed six sustained isometric ankle dorsiflexion contractions at 30% maximal voluntary torque, three under single-task conditions and three during concurrent serial number subtraction. High-density surface electromyography was recorded from tibialis anterior, and motor unit spike trains were decomposed and tracked across trials. Outcomes included torque coefficient of variation, mean discharge rate, inter-spike interval coefficient of variation, and intramuscular coherence in the delta (1-5 Hz), alpha (5-15 Hz), and beta (15-35 Hz) bands. ResultsSarcopenic individuals had worse torque steadiness (increased torque coefficient of variation) than controls (45-84%) and athletes (39-105%) during single-task, which worsened further (+35% relative to baseline) during dual-tasking. Mean discharge rates (proxy of neural drive) slightly increased during dual-tasking in all groups by [~]2.6%, with no between-group differences. Discharge rates coefficient of variation (Proxy of neural control unsteadiness) increased 5.5% in sarcopenia, was unchanged in controls, and decreased 4.1% in athletes during dual-tasking. Delta-band coherence decreased 5.5% during dual-tasking across all groups. Alpha-band coherence increased only in sarcopenia during dual-tasking (20.6%). Beta-band coherence increased 20.6% in sarcopenia but decreased 3.6% in controls and 3.8% in athletes during dual-tasking. ConclusionsOlder adults with sarcopenia exhibit poorer force and neural control steadiness, and both deficits worsen under cognitive load. These changes are accompanied by alterations in common synaptic input, particularly an increase in physiological involuntary tremor-related oscillations (alpha band), which contribute to greater force unsteadiness. Neural control unsteadiness during dual-task performance may therefore represent a neural feature of sarcopenia-related functional impairment. Assessing neuromuscular control during cognitively demanding tasks may improve detection of neural dysfunction and identify mechanistic targets for interventions to reduce mobility impairment and fall risk. These findings support expanding muscle-centric views of sarcopenia to include neural mechanisms of motor control.

ABSTRACT Background: Athletes who return to soccer after anterior cruciate ligament reconstruction (ACLR) remain at elevated risk of secondary injury despite meeting conventional discharge criteria, and neuromuscular deficits in the reconstructed limb are known to be exposed by fatigue. Objective: To determine whether match-play fatigue differentially affects muscle stiffness, countermovement jump (CMJ) force symmetry, and rate of force development (RFD) asymmetry between soccer players with a history of ACLR and uninjured teammates. Methods: A prospective, cross-sectional, matched-control study enrolled 128 competitive soccer players (64 ACLR, 6-22 months post-surgery; 64 uninjured controls) across five recruitment waves (February-June 2026). Bilateral CMJ peak vertical force, jump height, RFD, and myotonometric stiffness of the rectus femoris (RF), vastus medialis (VM), and biceps femoris (BF) were recorded immediately before and after a standardized competitive match. Fatigue was quantified from second-half heart rate (percentage of age-predicted maximum) and end-match rating of perceived exertion (RPE). Within-group pre-to-post changes were evaluated with paired t-tests, between-group differences in the magnitude of change with independent-samples t-tests, and associations between fatigue indices and asymmetry changes with Pearson correlations. Results: Match play reduced CMJ limb symmetry index (LSI) in both groups, but the decline was more than three-fold greater in the ACLR group, 92.6% (SD 5.4%) to 85.1% (SD 7.1%), than in control group, 97.3% (SD 3.9%) to 95.0% (SD 4.2%), group-by-time difference, p < 0.001, (d = 0.64). RFD asymmetry approximately doubled in the ACLR group, 10.6% (SD 4.1%) to 17.6% (SD 6.5%), compared with a smaller rise in control group, 4.6% (SD 2.4%) to 6.3% (SD 3.7%); p < 0.001, d = 0.77). Involved-limb stiffness losses in the ACLR group exceeded those of controls for the RF (-21.2 vs. -9.2 N/m, p < 0.001), VM (-17.7 vs. -6.1 N/m, p < 0.001), and BF (-13.3 vs. -6.6 N/m, p < 0.001), whereas uninvolved-limb stiffness losses did not differ between groups (all p > 0.05). Fatigue markers (heart rate, RPE) were not significantly correlated with the magnitude of individual asymmetry change (|r| [&le;] 0.18, p > 0.15). Conclusions: In competitive soccer players 6-22 months after ACLR, match-play fatigue selectively compromises stiffness and explosive force output of the reconstructed limb, widening inter-limb asymmetries beyond what is seen in uninjured teammates, even though global cardiovascular and perceptual fatigue were comparable between groups. These findings suggest that return-to-sport testing performed only in a rested state may underestimate residual neuromuscular deficits, and support fatigue-inclusive assessment protocols before athletes are cleared for unrestricted competition. Abbreviations: ACL: anterior cruciate ligament, ACLR: anterior cruciate ligament reconstruction, BF: biceps femoris, CMJ: countermovement jump, HRmax: maximum heart rate, LSI: limb symmetry index, RF: rectus femoris, RFD: rate of force development, RPE: rating of perceived exertion, RTS: return to sport, VM: vastus medialis, SD: standard deviation. Keywords: Anterior cruciate ligament reconstruction, muscle fatigue, muscle stiffness, countermovement jump, limb symmetry index, rate of force development, soccer, return to sport.

PurposeConsistently performing at the highest level in golf requires a complex interplay of physiological and psychological attributes, with success often defined by razor-thin margins. Sleep characteristics and cardiac autonomic function, reflected by resting heart rate (RHR) and heart rate variability (HRV), are key indicators of recovery and readiness to perform. Yet, their relevance to elite golf performance remains largely unexplored. MethodsWe analyzed wearable-derived longitudinal data from 389 professional tour-level golfers across 521 competitive events (2017-2025), encompassing 35,140 nights of sleep and biometric monitoring. Key metrics included sleep duration (7.2{+/-}0.7hrs), sleep consistency (69.1{+/-}6.9%), RHR (55.9{+/-}7.9bpm), HRV (64.2{+/-}28.1ms), and a composite Recovery score (59.1{+/-}9.9%). Golf performance (total score, great shots, poor shots, strokes gained) was extracted from a subscription-based database. Linear mixed-effects models assessed both between-person differences and within-person season-to-season changes, adjusting for age (34.1{+/-}9.1yrs), height (1.81{+/-}0.07m), and weight (83.2{+/-}10.6kg). ResultsGolfers with superior sleep and biometric profiles consistently performed better, both between and within individuals (Ps<0.05). Between individuals, each additional hour of sleep was associated with a lower score (b=-0.522), as was a 10-percentage point increase in sleep consistency (b=-0.382), a 1bpm lower RHR (b=-0.038), and a 10-percentage point increase in Recovery (b=-0.476). Within athletes, season-to-season improvements in sleep consistency (b=-0.193 per 10-percentage points), HRV (b=-0.016 per 1ms), and Recovery (b=-0.238 per 10 percentage points) were also associated with lower scores (Ps<0.05). ConclusionsSleep and measures of cardiac autonomic function are associated with performance in elite golf. Both individual differences and within-athlete improvements were linked to success, highlighting the potential role of sleep, resting heart rate, and heart rate variability in optimizing performance at the highest level of sport.

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

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.

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.

BackgroundIn patients with chronic coronary syndromes (CCS) increased ventilation/carbon dioxide production ([V]E/[V]CO2) slope has been found to predict disease progression and mortality similarly to patients with heart failure (HF), however, chemosensitivity has rarely been assessed in patients with CCS. MethodPatients with CCS, HF with reduced ejection fraction (EF<50%), old healthy (45+ years) and young adult healthy controls (<35 years) were recruited. For patients, a [V]E/[V]CO2 slope [&ge;]36 was an inclusion criterion. The Duffin rebreathing method was used to determine the resting end-expiratory partial pressure of carbon dioxide (PETCO2), ventilatory recruitment threshold (VRT) and slope (sensitivity) during a hyperoxic (150 mmHg O2) and hypoxic (50 mmHg O2) rebreathing test to determine central and peripheral chemosensitivity. ResultsIn patients with CCS, HF, and old and young controls, median [V]E/[V]CO2 slopes were 40.2, 41.3, 30.5 and 28.0, respectively. Both patient groups had similarly reduced hyperoxic VRT (at PETCO2 42.1 and 43.2 mmHg) compared to 46.0 and 48.8 mmHg in the old and young controls. Neither hypoxic VRT nor hyper- or hypoxic slopes were significantly different in patients compared to controls. Both patient groups had lower resting PETCO2 than controls, but only patients with HF had increased breathing frequency and rapid shallow breathing at rest. ConclusionIn patients with cardiac disease and excess ventilation, central chemoreflex VRT was reduced independently of the presence of heart failure. Low VRTs were related to resting excess ventilation in patients with CCS or HF, however, rapid shallow breathing was present only in patients with HF. Clinical perspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIExcess ventilation during exercise and heightened chemosensory reflexes may be present not only in patients with HF but also in patients with CCS. This suggests that there is a gradual derangement of neurologic and/or hormonal factors leading to excess ventilation before the establishment of HF. C_LIO_LIIn patients with excess ventilation during exercise there is also excess ventilation at rest. C_LIO_LIExcess ventilation in patients with CCS does not show the rapid shallow breathing pattern that is typical for patients with HF. C_LI What are the clinical implications?O_LIWhile excess ventilation during exercise causes dyspnoea with associated negative effects on exercise tolerance and quality of life,1 excess ventilation at rest has been poorly investigated. More research is warranted as physiologic consequences may be substantial with the large time spent at rest compared to exercise. C_LIO_LIThe finding that the threshold of PETCO2 at which ventilation starts to increase rather than the [V]E/PETCO2 slope is increased in patients with inefficient ventilation suggests electrolyte derangement as an at least contributing cause which may stimulate alternative treatments such as intravenous iron therapy.2 C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/24311710v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@149d9e2org.highwire.dtl.DTLVardef@17fc19dorg.highwire.dtl.DTLVardef@803364org.highwire.dtl.DTLVardef@ae18a7_HPS_FORMAT_FIGEXP M_FIG C_FIG

The supraspinatus is the most frequently injured rotator cuff muscle, but its anatomical characteristics such as larger size, complex fiber architecture, and a single exposed tendon have limited the development of reproducible ex vivo contractility assays. In this study, we establish a robust method for ex vivo assessment of murine supraspinatus contractile function and characterize its physiological properties across age and injury conditions. We additionally adapt a barium chloride (BaCl2)-induced injury protocol for the supraspinatus, an approach not previously described, to evaluate how acute myofiber degeneration affects muscle performance. Male C57BL/6 mice (4 months) underwent 1.2% BaCl2 injection directly into the supraspinatus to induce controlled myofiber necrosis, allowing comparison of contractile behavior between injured and uninjured muscles. Using our injury ex vivo physiological testing protocol, we quantified optimal length (L0), twitch kinetics, force-frequency responses, peak tetanic force, and preliminary fatigue-recovery dynamics. Our protocol consistently generated fused tetanic contractions and reproducible force-frequency curves in the supraspinatus. We observed differences in supraspinatus contractility between young and old mice, consistent with well-established age-related changes in hindlimb muscle contractility. In addition, BaCl2 injury produced significant impairments in contractility 48 hours post-injection, demonstrating the sensitivity of this method to acute muscle damage. This study provides a novel and reliable method for evaluating the contractile function of the murine supraspinatus muscle ex vivo, overcoming previous anatomical challenges.

ObjectiveExamine the association of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults. MethodsCross-sectional data from 829 older adults [&ge;]70 years was used. Total abdominal, subcutaneous, and visceral AT; and thigh muscle fat infiltration (MFI) was quantified by MRI. SM mitochondrial energetics were characterized using in vivo 31P-MRS (ATPmax) and ex vivo high-resolution respirometry (maximal oxidative phosphorylation (OXPHOS)). ActivPal was used to measure PA (step count). Linear regression models adjusted for covariates were applied, with sequential adjustment for BMI and PA. ResultsIndependent of BMI, total abdominal (standardized (Std.) {beta}=-0.21; R2=0.09) and visceral AT (Std. {beta}=-0.16; R2=0.09) were associated with ATPmax (p<0.01), but not after further adjustment for PA (p[&ge;]0.05). Visceral AT (Std. {beta}=-0.16; R2=0.25) and thigh MFI (Std. {beta}=-0.11; R2=0.24) were negatively associated with carbohydrate-supported maximal OXPHOS independent of BMI and PA (p<0.05). Total abdominal AT (Std. {beta}=-0.19; R2=0.24) and visceral AT (Std. {beta}=-0.17; R2=0.24) were associated with fatty acid-supported maximal OXPHOS independent of BMI and PA (p<0.05). ConclusionsSkeletal MFI and abdominal visceral, but not subcutaneous AT, are inversely associated with SM mitochondrial bioenergetics in older adults independent of BMI. Associations between ectopic AT and in vivo mitochondrial bioenergetics are attenuated by PA.

Mouse models of chronic intermittent hypoxia are widely used in research to understand the role of sleep apnea in disease pathogenesis. Mice exposed to periodic reductions in FIO2 model arterial desaturations observed in humans and recapitulate many comorbidities of sleep apnea. Here, we perform a detailed characterization and confirm reports that mice in room air experience spontaneous, periodic desaturation events. We measured peripheral oxygen saturation in the four mouse strains most commonly used in intermittent hypoxia research (C57BL/6J, CD1, BALB/c, and 129S1) and subjected them to conscious barometric plethysmography to measure oxygen desaturations and apneas simultaneously and took measurements across a range of fractional inspired oxygen (FIO2). As expected, all strains experienced periodic apneas that were followed by desaturations and decreasing FIO2 resulted in a reduction of spontaneous apneic events (p = 0.001). Surprisingly, most oxygen desaturations were not preceded by apneas or hypopneas, and mice experienced more desaturations at lower FIO2 (p < 0.001), despite less frequent apneas. Furthermore, we found strain differences in ventilatory response consistent with prior findings and a novel strain difference in 129S1 mice. These data suggest that spontaneous desaturations are caused not only by apneas and hypopneas but also by other mechanisms, independent of respiration. Our findings provide important context for mouse models of sleep apnea and associated diseases, and future work should explore the extent to which these findings are relevant in humans.

The mechanisms for the loss in limb muscle power in old (60-79 years) and very old ([&ge;]80 years) adults and whether the mechanisms differ between men and women are not well-understood. We compared maximal power of the knee extensor muscles between young, old, and very old men and women and identified the neural and muscular factors contributing to the age-related loss of power. 31 young (22.9{+/-}3.0 years, 15 women), 83 old (70.4{+/-}4.9 years, 39 women), and 16 very old adults (85.8{+/-}4.2 years, 9 women) performed maximal isokinetic contractions at 14 different velocities (30- 450{degrees}/s) to identify peak power. Voluntary activation (VA) and contractile properties were assessed with transcranial magnetic stimulation to the motor cortex and electrical stimulation of the femoral nerve. The age-related loss in power was [~]6.5 W{middle dot}year-1 for men (R2=0.62, p<0.001), which was a greater rate of decline (p=0.002) than the [~]4.2 W{middle dot}year-1 for women (R2=0.77, p<0.001). Contractile properties were the most closely associated variables with power output for both sexes, such as the rate of torque development of the potentiated twitch (men: R2=0.69, p<0.001; women: R2=0.57, p<0.001). VA was weakly associated with power in women (R2=0.13, p=0.012) but not men (p=0.191), whereas neuromuscular activation (EMG amplitude) during the maximal power contraction was not associated with power in men (p=0.347) or women (p=0.106). These data suggest that the age-related loss in power of the knee extensor muscles is due primarily to factors within the muscle for both sexes, although neural factors may play a minor role in older women. NEW & NOTEWORTHYThe accelerated age-related loss in power relative to the loss in muscle mass of the knee extensors was primarily due to factors altering the contractile properties of the muscle for both old and very old ([&ge;]80 yr) adults. The mechanisms for the decrements in power with aging appear largely similar for men and women, although neural factors may play more of a role in older women.

Ultrasound shear wave elastography can be used to characterize mechanical properties of unstressed tissue by measuring shear wave velocity (SWV), which increases with increasing tissue stiffness. Measurements of SWV have often been assumed to be directly related to the stiffness of muscle. Some have also used measures of SWV to estimate stress, since muscle stiffness and stress covary during active contractions. However, few have considered the direct influence of muscle stress on SWV, independent of the stress-dependent changes in muscle stiffness, even though it is well known that stress alters shear wave propagation. The objective of this study was to determine how well the theoretical dependency of SWV on stress can account for measured changes of SWV in passive and active muscle. Data were collected from six isoflurane-anesthetized cats; three soleus muscles and three medial gastrocnemius muscles. Muscle stress and stiffness were measured directly along with SWV. Measurements were made across a range of passively and actively generated stresses, obtained by varying muscle length and activation, which was controlled by stimulating the sciatic nerve. Our results show that SWV depends primarily on the stress in a passively stretched muscle. In contrast, the SWV in active muscle is higher than would be predicted by considering only stress, presumably due to activation-dependent changes in muscle stiffness. Our results demonstrate that while SWV is sensitive to changes in muscle stress and activation, there is not a unique relationship between SWV and either of these quantities when considered in isolation.

Walking energy consumption is higher in people with versus without a transtibial amputation, but the underlying reasons are poorly understood. Active prostheses that restore ankle power fail to decrease walking energy consumption, suggesting that there should be other reasons than a lack of ankle power. Transtibial amputation impacts walking stability, as evidenced by the increased fall risk, and there is an energetic cost associated with stabilizing walking. It is, however, unclear how transtibial amputation affects the energetic cost of stabilizing walking. We assessed the metabolic cost of stabilizing walking against treadmill belt speed perturbations (SD=0.13 m/s) in 16 subjects with and 23 subjects without a transtibial amputation at three walking speeds between 0.6 and 1.6 m/s. We focused on sagittal plane stability, as a transtibial amputation mainly affects modulation of the ankle torque, and this ankle strategy contributes most to sagittal plane control of walking at low speeds. Perturbations induced 0.24 W/kg larger increases in energy consumption across walking speeds in subjects with than without a transtibial amputation. Whereas mean reductions in step length in response to perturbations were similar between groups, individuals with an amputation increased step length variability of their intact leg more - especially at low speeds - than individuals without an amputation. As continuous control is required for unperturbed walking, an increased metabolic cost of stabilizing walking might explain - at least partially - the higher energetic cost of walking. These insights are important when seeking to reduce the metabolic cost of walking after transtibial amputation. NEW & NOTEWORTHYThe higher metabolic cost of walking in individuals with versus without a transtibial amputation is poorly understood, hindering the design of interventions. We demonstrated that transtibial amputation considerably increases the energy consumption for stabilizing walking in the sagittal plane and increases the reliance on step length adjustments to stabilize walking. This opens up perspectives for restoring walking energetics after amputation through prostheses that support sagittal plane stability.