Journal of Applied Physiology

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.

Background: Exercise-based cardiac rehabilitation (CR) improves peak oxygen uptake ([V]O2peak) in patients with coronary heart disease (CHD); however, whether women and men exhibit similar adaptations across the steps of O2 transport remains unknown. We aimed to compare the ventilatory and circulatory determinants of [V]O2peak changes between women and men with CHD following a structured exercise training program. Methods: A total of 28 women (27%) and 75 men (73%) with CHD, matched for age, body mass index, and [V]O2peak (% predicted), underwent maximal cardiopulmonary exercise testing (CPET) before and after 12 weeks of CR. [V]O2peak and minute ventilation ([V]E) were measured breath by breath. Heart rate and cardiac output ([Q]c)were assessed non-invasively using impedance cardiography. Exercise efficiency ({Delta}[V]O2/{Delta}W), alveolar ventilation ([V]A), ventilatory efficiency (OUES), O2 pulse, arteriovenous oxygen content difference (C(a-[v])O2) and gross muscular efficiency (W) were calculated using standard equations. Mixed model analyses (sex x time) were used to compare training-induced changes between sexes. Results: At baseline, values of [V]O2peak (absolute and normalized by fat free mass), [V]E, [V]A, O2 pulse, C(a-[v])O2, {Delta}[V]O2/{Delta}W, W were significantly lower in women than in men with CHD (group effect, p<0.01). [V]O2peak normalized by fat-free mass improved similarly in both sexes after CR (p<0.0001, no significant sex x time interaction). Pulmonary convection ([V]E, [V]A), ventilatory efficiency (OUES), circulatory convection ([Q]c, cardiac index, O2 pulse), and peripheral gross muscular efficiency (W) all improved similarly after CR in women and men (effect sizeXtime effect, p<0.05, no significant group x time interaction). The prevalence of responder categories did not differ between sexes (p=0.826). Conclusion: Women and men with CHD demonstrated equivalent O2 transport phenotype adaptations after CR, with comparable improvements across the O2 transport chain (pulmonary, circulatory, and peripheral determinants of [V]O2peak).

Background. Cardiopulmonary exercise testing (CPET) is a gold-standard test used to evaluate cardiopulmonary fitness and overall health by measuring physiological responses such as oxygen consumption during exercise. While traditional CPET warm-ups are typically low-intensity aerobic activities, alternative methods like coherence breathing may also prepare the body by influencing autonomic regulation. Breathing-based interventions have shown potential to improve heart rate recovery and performance, and heart rate variability (HRV) serves as a useful non-invasive indicator of autonomic nervous system activity. However, there is limited research on how brief breathing exercises before CPET affect outcomes. This study aims to investigate the effects of coherence breathing on oxygen uptake, HRV, and post-exercise heart rate recovery Objective. This study will aim to compare the acute cardiopulmonary and autonomic responses of coherence breathing versus spontaneous breathing immediately preceding cardiopulmonary exercise testing (CPET) in recreationally active healthy adults. Methods. This study will be a randomized counterbalanced crossover design. Healthy adults aged between 19 and 45 years of age will complete two separate CPETs over two non-consecutive test days (between 48 hours and 7days). During each visit, participants will complete five minutes of slow-paced coherence breathing (6 breaths per minute) or spontaneous breathing at normal breathing rate, followed by an incremental treadmill CPET protocol up to maximal exertion. HRV will be assessed at baseline, during the breathing interventions, and during cool-down for 5 minutes using the Emwave Pro Plus software. Gas exchange during the CPET protocol will be measured continuously using the VO2 Master Pro system. immediately after, and after 5 minutes of resting. The primary outcomes will be peak oxygen consumption and heart rate variability indices. Secondary outcomes will include heart rate recovery, peak heart rate, time to exhaustion, rate of perceived exertion and readiness, blood pressure, tidal volume, peak ventilation, and respiration rate. Analyses will use linear mixed-effects models and paired comparisons. Discussion. This protocol will determine whether pre-exercise coherence breathing can improve cardiopulmonary and autonomic nervous system responses to maximal performance. Findings may have practical implications for exercise testing and performance procedures as well as improving our understanding of pre-exercise breathing strategies for priming the autonomic and cardiopulmonary systems.

This study examined the utility of HRV detrended fluctuation analysis alpha-1 (DFA1) to assess readiness-to-train and exercise durability under varying acute training loads. Nineteen trained cyclists completed two 20-minute time-trials (TT) under rested and fatigued conditions. DFA1 was measured during a standardized warm-up (WU), 20-min TT, and standardized cool-down (CD). Power output (PO) and DFA1 responses were compared across conditions, and associations with performance and fitness (W/kg) were examined. DFA1 values declined with increasing WU and CD exercise intensity (p<0.001) and were significantly attenuated following the 20-min TT (p<0.001). While DFA1 profiles did not differ significantly between rested and fatigued conditions, lower pre-TT DFA1 was associated with reduced TT performance (p=0.022; r=0.55), suggesting relevance to training readiness. Additionally, an 18% decline in DFA1 between 10- and 20-min during the TT (p=0.031), and lower post-TT values at matched intensities were observed (p<0.001), indicating physiological perturbation from the 20-min TT. Fitter participants exhibited lower DFA1 values during the 20-min TT (p<0.001; r=-0.77), suggesting a greater capacity to sustain physiological stress. While DFA1 is responsive to exercise intensity and stress, offering potential to assess training readiness and durability, more robust fatigue protocols are needed to validate DFA1 as training load monitoring tool.

Blood flow restriction exercise (BFR-E) has gained popularity as a therapy used to improve muscle mass and strength in various clinical populations. However, the systemic and intramuscular responses to BFR-E are widely unknown. Here, we describe the functional and metabolic responses to BFR-E in our novel in vivo method of BFR-E in rats. Implementation of the model revealed increase in muscle mass and maximal strength in rats exposed to chronic BFR-E. Systemic metabolites related to glycolysis and redox metabolism were altered following acute BFR-E and metabolites related to amino acids and the TCA cycle were altered following chronic BFR-E. Moreover, transcriptomic analysis revealed a muscle-specific metabolic response to chronic BFR-E that coincided with morphological adaptations. Given the broad application of BFR-E in the rehabilitative setting, we examined the acute, systemic response to BFR-E in post-surgical human subjects. Semi-targeted metabolomic analysis revealed no significant alterations in circulating metabolites following acute BFR-E in humans, mirroring findings in acutely exercised rats. Together, these results suggest that the benefits of BFR-E are not mediated by acute systemic metabolic perturbations but instead arise from tissue-specific adaptations that develop with repeated exposure, establishing a conserved, translational framework for mechanistic investigation.

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.

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.

Mammalian lungs operate within a thoracic cage composed of parietal pleura, rib cage, skeletal muscle, and diaphragm, yet clinical ventilator metrics largely reflect the combined mechanics of lung and surrounding structures and the thoracic cage. We hypothesized that thoracic boundary conditions selectively alter measured lung biomechanics. We performed paired pulmonary function testing (FlexiVent) in C57BL6 mice of both sexes spanning development through adulthood, measuring quasi-static pressure-volume behavior and dynamic forced-oscillation parameters in vivo (supine, mechanically ventilated) and again ex vivo in the same lungs. In a subset, we additionally compared in vivo and ex vivo microCT-derived lung volumes, including a pressure-fixed ex vivo protocol using snap freezing at controlled inflation pressure. Quasi-static pressure-volume curves were similar between conditions, with near-identity at higher pressures and only modest divergence at low pressures, consistent with thoracic structures primarily modulating recruitment/de-recruitment rather than intrinsic elastic recoil. Maximal volume at 30 cmH2O showed strong in vivo-ex vivo correlation and minimal bias, and static compliance and PV-loop hysteresis exhibited small biases relative to reported disease-model effect sizes. In contrast, dynamic mechanics demonstrated a clear in vivo elevation of tissue damping (G) with only modest change in tissue elastance (H) and little change in Newtonian resistance (Rn), producing a meaningful increase in hysteresivity (G/H). This dissociation implicates frequency-dependent mechanical heterogeneity (time-constant mismatch/pendelluft) imposed or amplified by nonuniform thoracic loading. Ex vivo microCT enabled reliable whole-lung segmentation and correlated with ex vivo PFT volumes at matched pressures, whereas in vivo volumetry showed weaker agreement. These results indicate that thoracic structures contribute modest restriction but disproportionately increase dynamic dissipation and heterogeneity, suggesting that ex vivo functional testing and oscillometry-like metrics may better detect biomechanical changes inherent to lung parenchyma.

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.

Mass is a fundamental aspect of muscle contractile function, yet the inertial effects of inactive muscle mass is generally neglected in modeling and not quantified in studies on small muscles or isolated fibers. However, during submaximal contractions, inactive muscle tissue may take longer to be accelerated by active fibers, and may be subject to prolonged deceleration, both of which may potentially reduce force development and work output. We sought to test if inactive tissue mass imposes an inertial penalty on muscle performance, using in situ sinusoidal work-loop experiments on rat plantaris muscles. Regional fascicle dynamics, measured across supramaximal and submaximal levels of activation, showed that decreasing activation significantly reduced fascicle strain and increased both shortening and lengthening latency. Contrary to our predictions, however, reductions in work, beyond those explained by decreased fascicle strain, were negligible. Normalized work did not decline disproportionately relative to force, suggesting no clear inertial penalty on work at this muscle size. Our findings suggest that while inactive muscle mass influences the dynamics of submaximal contractions, its impact on work during submaximal contractions at small muscle sizes is limited.

Given its well-documented effects on human physiology, hypoxia has garnered increasing interest for its potential to enhance specific adaptations to exercise. However, the molecular response of skeletal muscle to exercise under normobaric hypoxia remains poorly understood. To address this gap in knowledge, ten healthy young males completed a crossover study in which exercise in hypoxia was compared to exercise in normoxia matched by either absolute or relative intensity. This design allowed us to identify shared transcriptomic responses across all three conditions, as well as changes that were specific to exercise intensity or hypoxic exposure. Skeletal muscle biopsies were collected before, immediately after, and at 3 and 24 hours following each exercise session, with RNA sequencing performed to assess changes in gene expression. Following exercise, a greater number of differentially expressed genes were observed in hypoxia compared to normoxia at 24 h post-exercise. This hypoxia-specific response involved the downregulation of multiple mitochondrial pathways and appears to be regulated by a transcriptional network comprising both positive and negative regulators of HIF-1 activity. These findings highlight the ability of normobaric hypoxia to influence exercise-induced gene expression and suggests that it may promote distinct molecular adaptations in skeletal muscle following longer-term training.

Background: Automatic tube compensation (ATC) was designed to compensate for the additional resistive load imposed by the endotracheal tube during spontaneous breathing. In ATC mode, the ventilator adds or subtracts the flow-dependent pressure drop across the tube during both inspiration and expiration so that tracheal pressure remains close to PEEP. Early prototype ventilators achieved true tracheal-pressure control and showed physiological and clinical benefits, but clinical studies with commercial systems have failed to confirm these earlier findings. A 2003 bench study found that commercial ventilators provided, at best, only partial tube compensation, unlikely to result in meaningful clinical benefit. We therefore tested whether this limitation has been remedied in contemporary ICU ventilators. Methods: We performed a bench comparison of five commercial ICU ventilators and an ATC prototype ventilator designed to accurately compensate for the flow-dependent resistance over a wide range of flow rates. An active lung simulator generated spontaneous breathing patterns with weak, moderate, and strong inspiratory efforts at different PEEP levels. We tested each breathing pattern through endotracheal tubes with inner diameters of 7 and 8 mm, and measured airway pressure, tracheal pressure, and flow during CPAP with and without ATC. Breathing through the tube against open atmosphere served as a zero-PEEP/T-piece reference. Results: In CPAP mode, the commercial ventilators showed flow-dependent airway-pressure deviations, amounting to a substantial added resistance of 1.5 - 6.5 mbar/(L/s), whereas the ATC prototype ventilator imposed an added resistance of only 0.6 mbar/(L/s). In ATC mode, the commercial ventilators reduced the resistive load by no more than by 25%, and large tracheal-pressure deviations remained, especially at higher inspiratory effort and during expiration. In some cases, the residual load during ATC was even greater than the load during unsupported breathing through the tube. By contrast, the ATC prototype ventilator maintained tracheal pressure close to PEEP throughout the breathing cycle and eliminated on average 79% of the tube-related resistive load. Conclusions: In the commercial ventilators evaluated in this study, the defining physiological objective of ATC was only partially achieved. Therefore, clinical benefits previously reported for tracheal-pressure control support should be interpreted with caution when applied to commercial ATC implementations, unless effective tube compensation has been demonstrated under relevant conditions. These findings suggest that more advanced control approaches, such as those implemented in the ATC prototype ventilator, may be required to achieve consistent and physiologically accurate tube compensation.

The endotracheal tube resistance dominates the total airway resistance in most intubated patients. Mucus deposition and biofilm formation can rapidly increase tube resistance and thereby contribute to serious ventilatory impairments, including dynamic hyperinflation, intrinsic PEEP build-up, added work of breathing, and patient-ventilator asynchrony. During controlled mechanical ventilation, an increased tube resistance can be inferred from the difference between peak and plateau pressure, but this approach fails during pressure-supported spontaneous breathing. Here, we present a method that estimates the linear and nonlinear components of tube resistance from naturally occurring airway pressure and flow fluctuations at the airway opening, without a tracheal pressure sensor and without applying mandatory forced oscillations. This is achieved by solving the equation of motion using band-pass filtered airway pressure and flow signals. Band-pass filtering isolates the relevant resistive and inertive pressure losses across the tube by removing slow contributions from muscle pressure and lung elastance as well as high-frequency noise. The method accurately recovers both linear and nonlinear tube resistance parameters with < 10% error and < 2% bias. Moreover, it enables real-time implementation of full Automatic Tube Compensation (ATC), even in the presence of severe tube obstructions. Continuous estimation of endotracheal tube resistance from naturally occurring airway pressure and flow fluctuations enables real-time detection of clinically relevant tube narrowing and may help improve patient safety, reduce patient-ventilator asynchrony, and facilitate weaning.

Skeletal muscles secrete a variety of cytokines in response to inflammatory stimuli such as lipopolysaccharide (LPS); however, the contributions of resident macrophages or other non-muscle cells to the secretory responses are not well understood. To determine the potential impact of resident macrophages to inflammatory cytokine production, we tested the LPS responsiveness of isolated mouse soleus muscle when a critical toll receptor adapter protein (Myd88) was knocked down only in myeloid-derived cells within the muscle (e.g. resident macrophages). The phenotype is referred to as LyzMyd88-/- ; the litter mate controls were Myd88fl/fl. In solei from LyzMyd88-/- mice, cytokine secretory rates for interleukin-6 (IL-6) and keratinocyte-derived cytokine (KC, CXCL1) were significantly reduced to 56.3%, and 60.6% of control, respectively, over the first hour of LPS exposure. In the second hour, secretion of granulocyte colony stimulating factor (G-CSF), IL-6, KC(CXCL1) and monocyte chemoattractant protein-1 (MCP-1, CCL2) were greatly elevated by 5-10-fold in both phenotypes compared to the first hour. However, only MCP-1 secretion was decreased to 70.6% of control in the second hour. We also tested the secretory response to buffer containing 1% sterile mouse plasma because dilute plasma is known to amplify the responses of macrophages to LPS. Treatment with 1% plasma alone affected baseline measures of some cytokines but resulted in no further increases in secretion during either hour of exposure. However, small and gradual increases in secretory rates were observed for several cytokines over the study period, with or without plasma, with the largest responses seen in IL-6 and KC. Overall, the results are consistent with a significant early contribution of myeloid-derived, resident immune cells to the cytokine secretory responses of intact oxidative skeletal muscle. In addition, small quantities of plasma in the buffer have no independent stimulatory effects on cytokine secretion

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.

Muscle force sharing during locomotion is influenced by the mechanical demands of movement and the contractile properties of synergistic muscles. In cats, plantarflexor muscles exhibit distinct functional specialization, with the slow-fibred soleus maintaining relatively constant force across conditions while faster muscles such as the plantaris and gastrocnemius increase force production with increasing locomotor demand. However, it remains unclear whether similar force-sharing patterns occur in larger animals with different musculoskeletal designs. Therefore, the purpose of this study was to examine force sharing between the superficial digital flexor (SDF) and medial gastrocnemius (MG) muscles during treadmill locomotion in sheep. Tendon buckle force transducers were surgically implanted on the SDF and MG tendons of seven sheep, and in vivo muscle forces were recorded during walking and trotting across different speeds and inclines. Both muscles increased force with increasing speed and incline; however, speed had a substantially greater effect than incline. The SDF consistently produced greater absolute force than the MG across all conditions, whereas the MG exhibited slightly larger relative increases in force with increasing speed. Time to peak force decreased with increasing speed in both muscles, although the SDF reached peak force later in stance than the MG across conditions. In contrast to the distinct specialization observed in cats, neither muscle displayed a relatively condition-independent, soleus-like force contribution. These findings suggest that force sharing in sheep is more distributed across synergistic muscles and may reflect the influence of musculoskeletal design, tendon compliance, and mixed fibre-type composition on muscle function in larger species.

ObjectivesTo determine whether early functional severity at presentation explains variability in return to sport (RTS) after ankle sprain in young athletes, compared with sprain subtype and injury mechanism. DesignRetrospective cohort study. MethodsAthletes aged [&le;]22 years with acute ankle sprains were identified from a prospectively maintained institutional database. Surgically treated cases were excluded. Functional severity at presentation was classified into three grades based on the ability to continue sports participation and ambulate immediately after injury. Injury mechanisms were categorized as high-energy deceleration (HED) or non-HED. RTS was analyzed as time to return and as prolonged RTS ([&ge;]4 weeks). Multivariable logistic regression was performed to identify factors independently associated with prolonged RTS. ResultsA total of 437 cases were included. Median RTS was 2.0 weeks (interquartile range, 0.0-4.0), and prolonged RTS occurred in 33.0% of cases. RTS duration increased stepwise with greater functional severity (p < 0.001). In multivariable analysis, functional severity was strongly associated with prolonged RTS (Grade 2: adjusted odds ratio [OR], 3.58; 95% confidence interval [CI], 2.07-6.19; Grade 3: adjusted OR, 24.53; 95% CI, 10.67-56.43; p < 0.001), and age was also independently associated (adjusted OR, 1.19 per year; 95% CI, 1.11-1.27; p < 0.001). Sprain subtype and injury mechanism were not independently associated with RTS after adjustment. ConclusionsEarly functional severity at presentation is the primary determinant of RTS after ankle sprain in young athletes. Apparent differences related to sprain subtype and injury mechanism are largely explained by initial functional impairment.

Age-related reductions in muscle fiber size and contractile function, particularly in fibers expressing fast myosin heavy chains, contribute to declines in whole-muscle power. However, methodological limitations in estimating fiber size during contractile experiments have likely contributed to conflicting findings regarding whether reduced single-fiber force and power in older adults reflects their smaller size and/or impaired intrinsic contractile function. To address this, we coupled single-fiber contractile experiments with 3D-imaging in 7 young (19-40yrs) and 6 older (69-84yrs) males to assess intrinsic contractile function and compare agreement between 3D-derived cross-sectional area (CSA) and CSA estimates obtained either in air or solution. Fast fiber CSA from older males were [~]28-45% smaller across measurement conditions compared with young, whereas slow fiber CSA did not differ. Accordingly, absolute force and power of fast fibers were 41% and 37% lower. When normalized to CSA from measurements in air or 3D-imaging, size-specific force and power either did not differ or were greater in older adults, indicating preserved intrinsic contractile function in both fiber types. This was supported by no age-related differences in the rate of tension redevelopment (ktr), a size-independent measure of intrinsic contractile function. In contrast, size-specific force and power calculated using solution-based CSA estimates were lower in older compared with young adults, and Bland-Altman analyses demonstrated the poorest agreement between solution-based and 3D CSA measurements. These findings indicate that intrinsic contractile function is preserved with aging and suggest that methodological differences in CSA measurement contributes to the disparate findings in the literature.

Pedalling cadence during an acute eccentric cycling exercise altered physiological and perceptual responses. We examined the influence of cycling cadence on neuromuscular adaptation induced by a 6-week eccentric cycling training period. Eighteen participants performed training (eighteen sessions) at a cadence of 30 or 60 rpm over six weeks. Power output was the same between the two groups. Perceived effort and heart rate were recorded at each training session. Muscle pain and fatigue were reported the day after each session. Maximal voluntary contractions torque, as well as concentric and eccentric cycling efficiency, were assessed before and after training. Additionally, the loss of maximal voluntary isometric torque was assessed after the first and last training sessions. Heart rate and perceived effort increased in the second week of training and then plateaued, with no difference between groups. Muscle pain and fatigue remained low throughout the training, with no difference between groups. Isometric (+28%) and eccentric (+13%) maximal voluntary torque of knee extensor muscles increased regardless of training cadence. Concentric maximal voluntary torque increased for the group pedalling at 60 rpm only (+21%). Cycling efficiency was improved in eccentric mode only (+43%), with no difference between the two training groups. Finally, the voluntary isometric torque loss induced by the first and last sessions were similar. While six weeks of eccentric cycling training improved neuromuscular and functional capacities, cadence had no observable effect. This finding suggest that patients could choose their preferred cadence to obtain better adherence to the rehabilitation program without altering the adaptations.

Context: Although knee extensor and flexor strength deficits are well-documented after anterior cruciate ligament reconstruction, limited data exist characterizing how strength recovery evolves over time. Understanding the temporal patterns of recovery, and how they differ by autograft type, is critical for optimizing rehabilitation and return-to-sport decision-making. Objective: To characterize temporal trends in knee extensor and flexor strength recovery during the first year post-ACLR and evaluate differences between patellar tendon and hamstring tendon autografts. Design: Case series. Setting: Sports physical therapy clinics within a large health system. Participants: Five hundred three patients (17.8 {+/-} 3.0 y) who underwent primary reconstruction with either patellar tendon or hamstring tendon autografts and completed a combined 730 return-to-sport tests within 12 months postoperatively. Main Outcome Measures: Normalized peak isokinetic concentric knee extension and flexion torques for involved and uninvolved limbs, and normalized symmetry indices for knee extension and flexion strength. Results: Knee extension strength on both limbs and extension strength symmetry improved over time. Patients with hamstring autografts demonstrated superior involved leg knee extension strength and better extension strength symmetry compared with those receiving patellar tendon autografts, although uninvolved leg strength was similar between autografts. Knee flexion strength on both limbs and flexion strength symmetry also improved over time. Patellar tendon autograft patients exhibited greater strength symmetry, despite no between autografts for flexion strength for the involved or uninvolved limb. Conclusions: Autograft significantly influences muscle strength recovery following anterior cruciate ligament reconstruction. Hamstring tendon autografts are associated with superior recovery of knee extension strength and strength symmetry compared to patellar tendon autografts. These findings underscore the need for graft-specific rehabilitation strategies and earlier identification of patients at risk for delayed recovery.