Journal of applied physiology最新文献

Cardiopulmonary exercise testing (CPET) is frequently requested in the hope that detecting the maximal limits of cardiovascular or respiratory function will provide clinically relevant information on the genesis of exertional dyspnea. We provide a concise review of emerging evidence that analyzing whole-test data, accounting for the dynamic (mis)match between requirements and capabilities (i.e., progressive reserve depletion), is more accurate and valuable for clinical decision-making than the traditional respiratory limitation paradigm. In this context, a pattern of excessive breathing emerges when heightened inspiratory muscle activation is fully translated into increased ventilation in the absence of mechanical restraints, such as reduced PaCO₂, increased physiological dead space, or high CO₂ output. Conversely, constrained breathing results from impediments to tidal volume expansion, imposed by the prevailing inspiratory capacity, which hinders ventilation despite increased inspiratory muscle activation. Based on sex- and age-adjusted standards for submaximal 0-10 Borg dyspnea-work rate and dyspnea-ventilation, dynamic ventilatory reserve-work rate, and dynamic inspiratory reserve-ventilation, the practitioner can readily identify whether excessive and/or constrained breathing can explain the subject's exertional dyspnea. Regardless of the precise mechanism of excessive breathing, therapeutic efforts should primarily focus on reducing the sources of increased afferent ventilatory stimuli. The identification of constrained breathing should prompt interventions to improve inspiratory reserve volume. This pragmatic approach to clinical CPET interpretation focuses on dyspnea as a treatable trait across physiological and disease states, aiming at providing cogent explanations for the symptom in light of the pre-test likelihood of abnormality.

Marathon and ultramarathon runners commonly exhibit post-race rises in biomarkers of acute kidney injury. While these perturbations are generally transient and resolve without treatment, rare but serious cases of clinically significant kidney injury in endurance athletes have been documented post-race. The purpose of this mini-review is to discuss the recent literature demonstrating a link between prolonged endurance running and acute kidney injury risk. We present the following: 1) the primary mechanisms by which endurance exercise contributes to acute kidney injury; 2) factors that may modulate kidney injury risk in endurance athletes; 3) recommendations and considerations for field-based studies; and 4) clinical implications and event specific considerations. In brief, hemodynamic, muscular, gastrointestinal, and hydration stressors collectively contribute to increased risk for acute kidney injury during prolonged endurance running. Additionally, there are several extrinsic (e.g., net elevation, temperature, humidity), intrinsic (e.g., biological sex, age, fitness), and behavioral (e.g., event hydration practices, training status) factors that likely contribute to the heterogeneous responses observed in athletes. Field studies offer unique ecological insight but introduce logistical challenges that are far less controlled than laboratory environments and therefore require important methodological considerations. Longitudinal studies are needed to determine whether repeated episodes of subclinical kidney stress contribute to any long-term decline in kidney function in habitual endurance runners or athletes.

Direct recordings from human motoneurons are not feasible; therefore, researchers have developed indirect methods to estimate postsynaptic potential profiles, i.e. the functional inhibition or excitation, on firing motor units. Surface and intramuscular electromyography have shown that the duration of the functional inhibition varies depending on the neural circuit investigated and is influenced by stimulus intensity and muscle activity level. This study aimed to standardise the estimation of functional inhibition durations across three distinct spinal and brainstem circuits by leveraging the known dependence of inhibition duration on background motor unit discharge rate. We analysed data from previous rat brain slice experiments in which known currents were injected into regularly discharging motoneurons. Regression of injected inhibition duration against discharge rate revealed a strong predictive relationship when extrapolated, accurately converging on the known duration. Specifically, this regression yielded the actual inhibition duration at a discharge rate of 0.98 imp/s [range: 0, 5.91 imp/s]. Building on these findings, we conducted three inhibition paradigms in human volunteers, targeting the masseter inhibitory reflex, the cutaneous silent period and recurrent inhibition mediated by Renshaw cells. Using extrapolated correlation plots of motor unit discharge rate versus functional inhibition duration, we derived discharge rate-independent inhibition durations. All three circuits demonstrated longer inhibition duration ranges than previously reported. This standardised approach enables more accurate estimation of inhibition duration across various circuits, independent of discharge rate. It holds promise for clinical applications in the early diagnosis and monitoring of neurological disorders affecting inhibitory circuits.

Endometriosis is a systemic inflammatory disease known to increase the risk of cardiovascular disease. The inducible form of cyclooxygenase (COX), COX-2, is an inflammatory enzyme upregulated in endometriosis with COX metabolites having potent effects on platelet aggregation and neurovascular control. The purpose of this study was to determine if COX activity modulates mechanisms of platelet aggregation and neurovascular control in patients with endometriosis. We hypothesized that women with endometriosis (Endo) would demonstrate augmented platelet aggregation and anodal current-induced vasodilation (a method of inducing COX-mediated vasodilation) compared with similarly aged healthy control women (HC), and that this difference would be mediated, at least in part, by COX activity. In a randomized, placebo-controlled design, 12 Endo and 9 HC participants underwent an anodal current-induced vasodilation protocol with following placebo or aspirin (650 mg). Laser Doppler flowmetry continuously recorded red blood cell flux and cutaneous vascular conductance (CVC = flux / mean arterial pressure) was quantified. A blood sample was taken for impedance aggregometry analysis and quantification of the COX metabolite thromboxane in plasma with enzyme linked immunosorbent assay. The Endo group demonstrated attenuated increases in CVC compared with HC (p < 0.01). There were no differences between groups in platelet aggregation characteristics (p ≥ 0.10, all reagents, all characteristics). There were no differences between groups in COX metabolites (TxB2 p = 0.27, PGE2 p = 0.70). Our findings suggest COX-mediated vasodilation is attenuated in women with endometriosis and that platelet activity is not different between women with endometriosis and healthy women.

Reductions in plasma volume (PV), a hallmark of spaceflight and its analog head-down-bed rest (HDBR), trigger compensatory releases of renin and aldosterone to promote fluid retention. Artificial gravity (AG) and exercise have been proposed to counteract PV reductions during HDBR, but optimal protocols remain undefined. We investigated how simultaneous exercise and AG affects volume-regulating hormones and PV during HDBR compared to exercise or sedentary control groups. We hypothesized that exercise+AG would protect PV and maintain volume-regulating hormones at pre-HDBR levels, outperforming exercise and sedentary control groups. Twenty-four healthy males (29±6 yr) underwent 60 days of 6° HDBR and were assigned to sedentary control (n=8), exercise (n=8), or exercise+AG (n=8) groups. Exercise group participants performed near daily 30-minute supine moderate-to-high-intensity interval cycling throughout HDBR, while exercise+AG participants performed the same exercise during 30 minutes of short-arm centrifugation with head-to-foot gravitational profiles based on resting G tolerance tests. Changes in PV, fluid-regulating hormones, and erythropoietin were assessed using carbon monoxide rebreathing and biochemical assays. HDBR reduced PV (p<0.001), blood volume (p<0.001), and hemoglobin mass (p<0.001) in all groups, and reductions were inversely correlated with an increase in active renin (all p<0.05; r_rm=-0.615, r_rm=-0.553, r_rm=-0.426, respectively). Erythropoietin was reduced at HDBR day 3 (p<0.001) irrespective of group. Exercise+AG responses did not differ from the exercise or control groups, with countermeasures failing to maintain PV or blunt fluid-regulating hormone release. These results contrast work showing benefit of gravity-like exposure after exercise on PV and suggests that AG should not be applied exclusively during exercise.

Loss of dystrophin alters the biomechanical properties of skeletal muscle, including stiffness. Stiffness is typically assessed passively in excised muscle, but here we present the development of an in vivo rheological method to assess the mechanical properties of the tibialis anterior muscle in anaesthetized wild-type (WT; dystrophin-positive) and mdx (dystrophin-deficient) mice using a custom-designed apparatus compatible with an MCR 702 rheometer. To characterize stiffness, compressibility, and elasticity, rheological testing included compressive and shear strain protocols, along with recovery and assessments following contraction-induced strength loss. Relative to WT mice, the tibialis anterior of mdx mice was thicker, stiffer, and less compressible. These genotype differences aligned with hydroxyproline content, a marker of fibrosis. Postdeformation recovery was impaired in mdx mice under shear strain, and eccentric contraction-induced injury further increased stiffness and energy dissipation in the tibialis anterior of mdx mice. This rheological platform maintained the in vivo integrity of the tibialis anterior muscle of mice and consistently showed that storage and loss moduli can sensitively detect the detrimental impact of dystrophin deficiency on the in vivo viscoelastic properties of skeletal muscle. This rheological platform, termed myomechanical profiling, could be a viable and sensitive tool for assessing muscle quality and mechanical behavior of skeletal muscle, where viscoelastic properties are affected by disease.NEW & NOTEWORTHY Myomechanical profiling was developed using cyclic rheometry to assess the in vivo viscoelastic properties of mouse skeletal muscle-the in vivo environment is maintained alongside high measurement sensitivity and spatial resolution, and the ability to apply deformation transverse to fiber orientation. Myomechanical profiling was trialed in dystrophin-positive and dystrophin-negative (model of Duchenne muscular dystrophy) skeletal muscle, and showed that the loss of the biomechanical protein dystrophin increased stiffness and impaired elasticity after compressive and rotational shear deformation.

In this study, we aimed to determine the association between changes in estimates of neural drive and global measures of electromyographic (EMG) amplitude elicited by short-term strength training. A cohort of 13 individuals performed 4 wk of strength training, which increased the maximal voluntary force (MVF) of the ankle dorsiflexors by approximately 14%, maximal root mean square (RMS) EMG amplitude for the tibialis anterior by approximately 42%, motor unit discharge rate by approximately 11%, and decreased motor unit recruitment threshold by approximately 10%. The increase in EMG amplitude during the submaximal contractions was observed at 50 and 70% of MVF (P < 0.05) but only for the absolute (µV) and not the normalized (% of MVF) root mean square (RMS) values. At the level of individual participants, it was possible to predict with moderate strength the changes in recruitment threshold and discharge rate after training (recruitment threshold vs. RMS, r = -0.55, P = 0.041; discharge rate vs. RMS, r = 0.56, P = 0.037, repeated measures correlations). These associations were not statistically significant when the EMG amplitude was normalized by the RMS values during the MVF contractions. Moreover, modeling the EMG with only the tracked motor units produced a strong correlation between the changes after training for both the reconstructed and measured EMG (r = 0.86, P < 0.001). These results demonstrate that the adaptations in neural drive experienced by individual participants after short-term (<1 mo) training interventions can be estimated from the absolute amplitude of multichannel EMG signals.NEW & NOTEWORTHY The absolute EMG amplitude estimated with high-density electrode grids can partially capture within-participant changes in motor unit discharge rates and recruitment thresholds, provided the intervention does not alter muscle fiber membrane properties. These adaptations, however, are not detectable in EMG signals normalized to peak values during maximal contractions. Consequently, global EMG analysis can serve as an approximate indicator of neural adaptations within participants during the early stages of strength training.

Sex differences in endurance performance are well established, but the magnitude of these differences appears smaller in ultraendurance events, particularly swimming. This study examined sex differences in solo English Channel swimming performances and assessed the influence of age and water temperature. A retrospective analysis included 2,593 unique solo English Channel swims (1,724 males and 869 females) recorded between 1875 and 2025. Swims were obtained from the Channel Swimming & Piloting Federation database. To minimize variability from noncompetitive crossings, analyses were restricted to the top 100 swimmers of all time within each age and water temperature subgroup. Sex differences were assessed across all finishers, among the top 100 swimmers, within age and water temperature categories, and over consecutive 5-yr periods. Across all swims, males were 2.2% faster than females (13.54 ± 0.06 h vs. 13.84 ± 0.10 h, P = 0.009). Restricting analysis to the top 100 swimmers, the sex difference was 7.2% (9.00 ± 0.08 h vs. 9.67 ± 0.08 h, P < 0.001). Sex differences increased with age, ranging from 5.2% in the 20- to 29-yr group to 26.5% among swimmers >60 yr. Males outperformed females across all water temperature categories, and the fastest swims for both sexes were observed at 17°C to 17.9°C. Male swimmers are faster than female swimmers in English Channel crossings, with differences most pronounced among top performers and older athletes. However, sex differences are smaller than those reported in ultraendurance running, suggesting that the unique environmental and physiological demands of open-water swimming partially attenuate male performance advantages.NEW & NOTEWORTHY This study leverages an experiment of nature framework to examine sex-based differences in ultraendurance swimming using English Channel performance data. Males were faster than females, with the greatest differences observed among older swimmers and top performers. Performance was optimal in moderately cool water temperatures (17-18°C). These findings highlight how naturally occurring endurance events provide unique opportunities to study physiological limits and the combined influences of sex, age, and environment on human performance.

Exertional dyspnea is the main symptom of chronic obstructive pulmonary disease (COPD). Based on the positive relationship between the levels of dyspnea (Borg score) and the electrical activity of respiratory muscles [electromyogram (EMG)] during an incremental cardiopulmonary exercise test, it has been suggested that respiratory EMG can provide a physiological biomarker for dyspnea. This study aimed to characterize the relationship between dyspnea and EMG during exercises simulating daily activities. Surface EMG was measured at two locations on the chest of 28 patients with COPD while they were performing constant-work rate cycling tests and walking/cycling exercises that were part of their rehabilitation program. Simultaneously, the level of dyspnea was assessed using the Borg score at several timepoints throughout the exercise sessions, along with respiration rate (RR), heart rate (HR), and transcutaneous oxygen saturation ([Formula: see text]). Patients completed each up to 10 such study visits during their 8-wk stay at the rehabilitation center (CIRO, the Netherlands). In total, 1981 Borg scores with associated EMG measurements were recorded during 263 study visits. A linear-mixed model was used to assess the relation of the Borg score with EMG while controlling for RR, HR, (type of) exercise, [Formula: see text], age, and sex. Random effects for patient and visit were included to account for correlation in the measurements. EMG had a highly significant association with the Borg score (P < 0.0001). Respiratory EMG and Borg score showed consistent positive correlations, of which the magnitude varied between patients. These results indicate that respiratory EMG can provide a physiological biomarker for dyspnea during activities of daily living in patients with COPD.NEW & NOTEWORTHY This study demonstrates that, even after controlling several physiological variables, electromyography (EMG) of the respiratory muscles is significantly associated with dyspnea, as assessed by the Borg scale in patients with chronic obstructive pulmonary disease (COPD) during daily activities. This finding suggests that respiratory EMG may serve as a physiological biomarker for dyspnea. Surface EMG measured on the chest offers valuable insights for assessing dyspnea, providing an additional, objective tool to capture the intensity of dyspnea during daily living.

Pulmonary surfactant is a vital component of respiratory physiology. Surfactant homeostasis is disrupted in various pulmonary disease states, and exogenous surfactant therapy has been proposed as a treatment to improve lung function and recovery. Although this therapy has demonstrated clinically significant benefit in neonatal respiratory distress syndrome, for adult patients with acute respiratory distress syndrome (ARDS), the evidence is inconclusive. To understand the potential shortcomings of past trials and potential opportunities for more effective exogenous surfactant use in ARDS, we review in detail past trials and literature involving exogenous surfactant therapy in adult patients with ARDS. We assess various factors that may have impacted trial results and propose potential solutions and areas for future research. Advances in surfactant research suggest a potential role for exogenous surfactant therapy for adult patients with ARDS.