Journal of applied physiology最新文献

Idiopathic hyperventilation syndrome (HVS) is a poorly understood condition with potential mechanisms involving altered CO₂ chemosensitivity, CO₂ store depletion, and reduced plant gain (PG). Twelve carefully selected patients with HVS (HVS+), diagnosed by symptoms, normal lung function, and a positive hyperventilation provocation test, were compared to 12 matched healthy controls (HVS-). All participants underwent a hypercapnic-hyperoxic challenge test (HHCT), assessing ventilatory and drive-to-breathe responses and dyspnea. Parameters included controller gain (β-slope), ventilatory and drive recruitment thresholds (VRT and DRT), extrapolated apneic and chemoreflex thresholds (AT and CT), CO₂ stores, PG, and peripheral sensitivity range (PSR = VRT-AT). Compared to HVS-, patients with HVS+ showed elevated baseline ventilation, ventilatory variability, drive-to-breathe, and dyspnea (all P ≤ 0.048). During HHCT, despite a similar β-slope, HVS+ exhibited a leftward-shifted ventilatory response curve, with lower AT and CT, expanded PSR, and reduced PG (all P ≤ 0.021), suggesting reduced CO₂ buffering and heightened peripheral chemosensitivity. While in HVS- baseline breathing patterns correlated closely with end-tidal CO₂ pressure and VRT, in HVS+ the ventilation magnitude and variability were associated with PG, PSR, and CO₂ stores (all P ≤ 0.048). Multivariate regression showed that PG was predicted by PSR, CO₂ stores, and their interaction. PG and ventilatory variability emerged as strong predictors of HVS+. These findings reveal a distinct ventilatory phenotype in HVS+ marked by increased reliance on peripheral chemoreflex inputs and disrupted CO₂ buffering capacity. PG and ventilatory variability emerged as strong predictors of HVS+ status, reinforcing their potential diagnostic value. These results support a novel pathophysiological model that warrants further investigation.NEW & NOTEWORTHY Patients with idiopathic hyperventilation syndrome (HVS) displayed preserved central chemosensitivity but altered ventilatory control at rest, characterized by elevated ventilation, increased variability, and a leftward-shifted hypercapnic response. These features were strongly associated with peripheral chemosensitivity, CO₂ stores, and reduced plant gain, patterns not observed in controls. These findings support a novel integrative model in which altered CO₂ buffering and peripheral afferent inputs, rather than central mechanisms alone, contribute to ventilatory instability in HVS.

Even brief periods of physical inactivity can induce metabolic disruptions; however, the underlying cellular and molecular mechanisms initiating these alterations remain unclear. We investigated whole-body and skeletal muscle-specific metabolic responses to short-term inactivity induced by dry immersion (DI), a model of rapid physical deconditioning. Eighteen healthy men (age = 33.6 [SD 5.5] years, body mass index (BMI) = 23.3 [1.8] kg/m²) underwent five days of DI in a longitudinal within-subject design, with each participant serving as his own control. DI-induced inactivity reduced V̇o_2max (-7.4%, P = 0.003), fat mass [dual energy X-ray absorptiometry (DXA), -2.6%, P = 0.002], fat-free mass (DXA, -2.6%, P < 0.001), and quadriceps cross-sectional area (MRI, -2.8%, P < 0.001). Fat content increased in the liver (MRI, +21%, P < 0.001), but not in the muscles (MRI, +0.1%, P = 0.218). Urinary nitrogen excretion rose (+28%, P < 0.001), indicating increased whole-body protein catabolism. Fasting insulin (+46%, P = 0.009) and triglycerides (+14%, P = 0.013), as well as postprandial incremental glucose (+49%, P = 0.002) and insulin (+90%, P < 0.001) concentrations following a carbohydrate-rich meal were increased. Fasting and postprandial total lipid and carbohydrate oxidation measured by indirect calorimetry and adjusted for body composition remained unchanged (P > 0.05 for all). In differentiated myotubes isolated from vastus lateralis biopsies, insulin-stimulated Akt Thr308 phosphorylation (P = 0.03), in vitro glycogen synthesis assessed from U-¹⁴C glucose (P < 0.01), and the ability to suppress in vitro palmitate oxidation (1-¹⁴Cpalmitate) following incremental glucose concentrations were impaired (P = 0.02). The ability to increase palmitate oxidation when palmitate availability rises was not significantly altered. These results suggest that early intrinsic skeletal muscle cell changes may contribute to the onset of whole-body metabolic disorders induced by physical inactivity.NEW & NOTEWORTHY Five days of dry immersion led to reduced cardiovascular fitness, muscle atrophy, hepatic fat accumulation, and lower glucose tolerance. These alterations occur despite no detectable changes in whole body fat and carbohydrate oxidation following a carbohydrate-rich meal. In cultured primary myotubes, insulin action and metabolic flexibility (fuel switching) are impaired. Early alterations in intrinsic muscle cell metabolism likely reflect rapid epigenetic imprinting of satellite cells and may contribute to systemic metabolic disturbances induced by physical inactivity.

In very preterm infants, nonuniform lung aeration occurs when regions of the immature lung remain liquid-filled after birth, which restricts gas exchange to aerated lung regions. We have examined the effect of surfactant administration on the uniformity of lung aeration and the distribution of ventilation in mechanically ventilated preterm rabbits. Preterm kittens (28-29 days gestation; term: ∼32 days) were delivered by cesarean section and intubated via tracheostomy. Before the experiment, kittens were initially ventilated (intermittent positive pressure ventilation; iPPV) to achieve whole (both lungs) or partial (one lung) lung aeration. Kittens were then ventilated (volume targeted: 8 mL/kg) with or without an initial sustained inflation (SI), before surfactant. Lung aeration was measured before and after surfactant, using phase contrast X-ray imaging and plethysmography. iPPV alone was unable to aerate unaerated lung regions, resulting in regional overexpansion due to a marked nonuniform distribution of ventilation. Although a SI increased aeration of nonaerated lung regions, the effect of surfactant was markedly greater, resulting in aeration of previously unaerated lung regions and markedly reducing regional overexpansion. Surfactant administration soon after birth greatly increases the uniformity of lung aeration and distribution of ventilation in mechanically ventilated very preterm newborns.NEW & NOTEWORTHY Preterm newborns commonly receive intermittent positive pressure ventilation (iPPV) at birth, but the optimal approach that facilitates uniform lung aeration is unknown, particularly in a partially aerated lung. We have shown that surfactant administration to partially aerated lungs markedly enhances aeration of unaerated lung regions, which redistributes the incoming tidal volume to more evenly ventilate the lung. These experimental findings support the rationale to administer surfactant as soon as possible after birth in preterm infants.

This study examined the effect of the knee-joint angle on motor unit (MU) discharge properties of the vastii muscles and their modulation with contraction level. Twelve young adults performed unilateral isometric knee-extension contractions during three experimental sessions at either 25°, 55°, and 85° of knee flexion (full extension: 0°) in a randomized order. Each session involved maximal voluntary contractions (MVCs) followed by submaximal trapezoidal and triangular contractions at different levels relative to maximal voluntary torque (MVT). High-density surface electromyograms were recorded from vastus lateralis and medialis muscles and, subsequently, decomposed to obtain discharge timings of individual MUs. MVT was the greatest, whereas MU discharge rate (DR) during MVCs and submaximal contraction levels (≥30% MVT) was the lowest at the intermediate joint angle (55°). The highest DR during MVCs and high-level contractions (70% MVT), however, was at the most flexed knee position (85°), which was due to a greater DR increase 50%-70% MVT compared with 25° and 55°. The onset-offset DR hysteresis (ΔF), an estimate of persistent inward current contribution to motoneuron discharge, decreased with knee flexion and increased with contraction level, whereas the degree of motoneuron input-output nonlinearity (brace height) did not vary with joint angle but decreased with contraction level. At 85°, ΔF increased more and brace height decreased less with contraction level compared with 25° and 55°. These findings indicate that vastii MU DR and its modulation with contraction level vary with knee-joint angle, which could be partly explained by the modulation of motoneuron intrinsic electrical properties.NEW & NOTEWORTHY This study explored the relationship between motoneuron output to the vastii muscles at different knee-joint angles (quadriceps lengths) and isometric contraction levels. We showed that the motor unit discharge rate was lowest at the angle of the greatest absolute torque capacity, whereas the contraction-level-induced increases in discharge rate and motoneuron excitability were the greatest in the flexed position. These findings suggest that joint-angle-dependent adjustments in sensory feedback modulate motor control of the knee-extensor muscles.

Older adults walk with reduced ankle and greater hip mechanical output compared to young adults. This "distal-to-proximal redistribution" likely contributes to the greater metabolic energy expenditure during walking in older versus young adults. Because of the inverse relationship between ankle and hip use, functional electrical stimulation (FES) of the ankle extensors may increase ankle mechanical work and indirectly decrease hip mechanical work. Although FES increases stimulated muscle metabolism, bilateral soleus stimulation may restore more youthful walking kinetics without a detectable change in whole body metabolism because ankle extension requires less metabolic energy than hip extension. Ten young adults and 10 older adults walked on a treadmill at 1.25 m/s with and without FES bilaterally applied over the respective leg's soleus when the anterior-posterior ground reaction force exceeded +10% body weight. FES use altered walking mechanics and metabolic power similarly across age groups (all FES condition and age group interactions P ≥ 0.214). Across age groups, FES increased ankle mechanical power (P = 0.041) and redistributed mechanical work production to occur relatively more at the ankle and less at the hip (P = 0.010). The lower limb joint redistribution ratio of older adults walking with FES was not different from that of young adults during baseline (P = 0.785). Moreover, walking with FES increased metabolic power by 2% (P = 0.037). FES attenuated older adult distal-to-proximal redistribution and modestly increased whole body metabolic rate. Overall, FES applied to soleus muscles during walking affects users similarly across the lifespan, indicating that FES interventions ought to consider a person's functional needs, regardless of age.NEW & NOTEWORTHY Functional electrical stimulation (FES) attenuates the distal-to-proximal redistribution in older adult joint mechanics with a small increase in whole body metabolic rate. Furthermore, FES affects young and older adults similarly, suggesting that such stimulation paradigms can be prescribed based on user needs, independent of age.

Body sizes and shapes vary widely, even among healthy adults, resulting in diverse muscle sizes, strengths, and performance capacities. This study developed an artificially intelligent (AI) algorithm to segment individual muscles and bones from whole body MRI scans of 102 healthy adults (49 males, 53 females) aged 18-50 yr, generating three-dimensional (3-D) segmentations of 70 muscles and 13 bones spanning the upper limbs, trunk, and lower limbs. We quantified muscle volume, asymmetry, and fat fraction at whole body, regional, and individual-muscle levels, and examined how these properties correlate with body size and skeletal dimensions. Fat fraction and asymmetry varied across muscles and were generally similar between sexes; however, the distribution of muscle volume across the body differed between females and males. Across all predictors tested, total bone volume showed the strongest correlation with total muscle volume (r² = 0.85), followed by femur volume, height × mass, mass, height, and BMI. At the individual muscle level, the associated bone volume consistently explained more variance in muscle size than anthropometric predictors. Correlations between muscle volume and body-size parameters were significantly different between males and females, whereas bone-volume correlations showed no significant sex differences. These results suggest that skeletal dimensions-reflecting an individual's "frame size"-are stronger determinants of muscularity than body size metrics and explain the observed sex differences in muscle sizes. This work presents a comprehensive in vivo muscle-level dataset to date, introduces a novel framework for analyzing muscle-bone correlations, and provides reference data for applications from clinical diagnostics to athletic performance and musculoskeletal modeling.NEW & NOTEWORTHY This study presents the most comprehensive in vivo dataset of full-body muscle and bone volumes in healthy adults, showing that skeletal dimensions are the strongest predictors of muscularity, with height × mass emerging as the second-best predictor.

There is a metabolic cost associated with stabilizing walking, but it remains unclear to what extent stabilizing walking in the sagittal plane contributes to this cost. Furthermore, strategies for stabilizing walking in the sagittal plane vary with speed, but it is unclear whether this also leads to a speed-dependent metabolic cost of stabilizing walking. Here, we explored the metabolic cost of stabilizing walking in the sagittal plane across speeds and its relationship with control strategies. To this aim, we applied continuous treadmill belt speed perturbations (a standard deviation of 0.13 ms^-1) to 22 healthy individuals walking at 0.8, 1.2, and 1.6 ms^-1. We evaluated changes in metabolic energy consumption and control strategies between perturbed and unperturbed walking and explored relationships between energy consumption and control strategies. Perturbations induced larger increases in metabolic rate and changes in control strategies at slower than faster walking speeds, suggesting that walking is more robust against perturbations at faster speeds. Perturbations increased the metabolic rate by 16.7% at the slowest vs. 4.6% at the fastest walking speed. When perturbed, subjects took shorter, wider, and more variable steps and variability in ankle muscle activation increased, but most changes were larger at slower speeds. Metabolic rate increased more due to perturbations in individuals who reduced step length more, that is, relied more on anticipatory adjustments of the walking pattern. Our findings are especially relevant to explain the increased metabolic cost of individuals with mobility impairments, who often walk slower and have altered walking control.NEW & NOTEWORTHY Stabilizing walking requires more active control in the frontal than in the sagittal plane. Nevertheless, we demonstrated that there is a considerable energetic cost associated with stabilizing walking in the sagittal plane, especially at slower speeds. This cost is higher in individuals who adjusted their average walking pattern more when walking was perturbed. Diseases that affect both walking speed and control might therefore have a disproportionately large effect on the metabolic cost of walking.

Surgical hyoid repositioning (HR) improves upper airway (UA) patency. Tracheal displacement (TD) likely influences HR outcomes, and vice versa, due to hyoid-trachea connections. This study used computational modeling to investigate the influence of TD and HR (with fixation) on UA outcomes and the impact of a lower baseline hyoid position [obstructive sleep apnea (OSA) phenotype]. A two-dimensional (2-D) finite element model of the rabbit UA simulated TD and HR (with fixation) in different directions, separately and combined. Model outcomes included UA closing pressure (Pclose), area, anteroposterior diameter (APD), and soft tissue mechanics (stress/strain). Simulations were repeated with a more caudal baseline hyoid position. Compared with baseline (TD = HR = 0 mm), TD alone reduced Pclose by -34%, increased area by 21% and APD by up to 18%. HR alone (except caudal) improved outcomes, particularly anterior-cranial HR, which decreased Pclose by -106%, increased area by 32% and APD by up to 107%. TD + HR (except caudal) enhanced these outcomes, with TD + anterior-cranial HR further decreasing Pclose (-131%) and increasing area (55%) and APD (128%). A more caudal baseline hyoid position reduced the effect of TD + anterior-cranial HR on Pclose (-43%), area (49%), and APD (115%). Combined TD and HR (except caudal) improved UA outcomes beyond either intervention applied alone. A more caudal baseline hyoid position reduced these effects. This computational model of the rabbit upper airway suggests that optimizing OSA treatment outcomes could involve considering baseline hyoid position, degree of TD, and direction/extent of HR, with potential benefits from combining HR and TD-based approaches.NEW & NOTEWORTHY Computational simulations of the rabbit upper airway suggest that combining tracheal displacement with anterior-based hyoid repositioning, with fixation, improves airway outcomes more than either approach alone. However, a lower natural hyoid position, characteristic of obstructive sleep apnea (OSA), reduces these benefits. Optimizing OSA treatment may require considering the natural hyoid position, surgical hyoid repositioning direction/magnitude, and natural tracheal displacement range. A combined tracheal displacement-hyoid repositioning strategy may further improve airway patency in select cases.

Dietary nitrate ([Formula: see text]), a source of nitric oxide (NO), enhances muscle contractility in numerous populations, but it is still unclear whether young women also benefit. The efficacy of [Formula: see text] supplementation might vary with menstrual cycle phase, due to lower endogenous NO bioavailability when estradiol (E₂) is low. Using a double-blind, placebo-controlled, crossover design, we determined the effects of acute ingestion of 200 μmol/kg of [Formula: see text] (from concentrated beetroot juice) or placebo on muscle function in 12 normally menstruating women during the early follicular (EF) and late follicular (LF) phases of their cycle. Muscle function was determined through maximal knee extensions on an isokinetic dynamometer and electrical stimulation of the quadriceps, with menstrual phase confirmed through plasma hormone measurement. E₂ concentrations were significantly lower in EF versus LF (220 ± 90 vs. 583 ± 260 pM; P < 0.001), whereas progesterone levels did not differ. Despite this, dietary [Formula: see text] had no effect on maximal muscle power or velocity during either phase. Dietary [Formula: see text] also had no effect on unpotentiated or potentiated peak twitch torque, rate of torque development (RTD), rate of relaxation (RR), or the torque frequency relationship during either phase. However, the RTD was 2%-8% greater in the LF versus EF phase, especially in the unpotentiated state (P < 0.01). The RR was also 9% slower in the LF versus EF phase (P < 0.05). Variations in E₂ during the menstrual cycle seem to subtly influence muscle contractile function. Acute [Formula: see text] supplementation, on the contrary, has no apparent effect on muscle contractility in young women.NEW & NOTEWORTHY We determined the effects of dietary [Formula: see text] on muscle contractile function during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle. Although [Formula: see text] supplementation had no impact on muscle contractility, during electrically evoked twitches, the rate of torque development was greater, and the rate of relaxation was slower, in the LF phase. These findings enhance our understanding of how dietary [Formula: see text] and female sex hormones impact muscle contractile function.