J. Appl. Physiol. [JOURNAL]
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200 papers
Neurophysiological and perceptual responses to consecutive days of exhaustive high-intensity interval cycling are dissociated.
Zhang J, Morgan SJ, Pricop M … +4 more , Bannister K, Pageaux B, MacInnis MJ, Aboodarda SJ
J Appl Physiol (1985) · 2026 May · PMID 41996131 · Publisher ↗
The impact of performing consecutive high-intensity interval (HIIT) exercise sessions on psychophysiological responses remains unclear. We hypothesized that consecutive HIIT sessions would exacerbate neuromuscular functi...
The impact of performing consecutive high-intensity interval (HIIT) exercise sessions on psychophysiological responses remains unclear. We hypothesized that consecutive HIIT sessions would exacerbate neuromuscular function impairments, metabolic disruptions, and perceptual responses. Sixteen healthy participants (7 females) performed five consecutive days of HIIT (4:4 min cycling:rest intervals) to task failure. On , , and , transcranial magnetic and femoral nerve stimuli were delivered in the final minute of each interval to characterize corticospinal excitability. Immediately upon completion of each interval, neuromuscular fatigue was assessed by a maximal isometric voluntary knee extension coupled with superimposed and resting twitches. Cardiorespiratory and metabolic responses were measured throughout the exercise. Perceived fatigue, pain, breathlessness, and effort were recorded at the end of each work bout, using psychophysical scales. The total intervals completed were unchanged across the five days ( = 0.415). The decline in quadriceps resting twitch force was attenuated on compared with ( = 0.038) and ( = 0.020). Motor evoked potential normalized to maximal muscle compound action potential (i.e., corticospinal excitability) was lower on compared with ( = 0.044). Blood lactate concentration was lower ( < 0.001), and perceived fatigue ( < 0.001), effort ( < 0.001), pain ( = 0.002), and breathlessness ( < 0.001) were all higher on compared with . Overall, the five consecutive HIIT sessions resulted in less decline in resting twitch, decreased corticospinal excitability, and exacerbated perceptual responses. These results suggest increased perceptual responses observed after five consecutive days of HIIT exercise reflect fatigue-related central alterations rather than alterations at the muscle level. The psychophysiological mechanisms underpinning potential performance decrement or retention across consecutive exercise days are unknown. Here, we demonstrated that across five days of exhaustive interval cycling, a lesser reliance on anaerobic glycolysis-evidenced by lower lactate and blunted muscle twitch decline-appeared to counterbalance decreased corticospinal excitability and exacerbated perceptions of fatigue, pain, breathlessness, and effort. The elevated perceptual responses likely reflect a supraspinal compensatory mechanism allowing maintenance of performance.
The impact of cognitive stress on vascular response and force steadiness during a handgrip task in males and females.
Pereira HM, Battung EF, Keller NR … +3 more , Nolan M, Gigliotti A, Kellawan JM
J Appl Physiol (1985) · 2026 May · PMID 41989888 · Publisher ↗
Although activities of daily living often involve performing a stressful cognitive task simultaneously with a motor task, it is not well understood whether vascular tone and the control of force under these stressful con...
Although activities of daily living often involve performing a stressful cognitive task simultaneously with a motor task, it is not well understood whether vascular tone and the control of force under these stressful conditions differ from tasks performed in isolation (i.e., without the cognitive task) in males and females. Our goal was to determine the impact of performing a difficult cognitive task simultaneously with a handgrip task on forearm vascular conductance and force steadiness. Fifteen males (19-30 yr) and 15 females (18-30 yr) performed isometric contractions at 5%, 10%, and 20% of maximal voluntary contraction (MVC) in the presence and absence of a difficult math task (subtractions by 13). Mental math reduced force steadiness particularly at 5%, but not 10% and 20% of MVC (Δ: 0.8 ± 0.2 vs. 0.2 ± 0.1 vs. 0.01 ± 0.1% respectively, session × intensity: = 0.017) for males and females (session × intensity × sex: = 0.666). Vascular conductance relative to lean mass was reduced in the presence of mental math at lower contraction intensities (Δ: 0.47 ± 0.2 vs. 0.46 ± 0.2 vs. 0.12 ± 0.2 mL × min × kg × mmHg for 5%, 10%, and 20% MVC, respectively; session × intensity: = 0.039), and the reductions were negatively associated with MVC. Although males and females had similar reductions in force steadiness in the presence of mental math, individuals with lower MVC, often females, were more likely to show reductions in vascular conductance in the presence of cognitive stress. The impact of performing a stressful cognitive task simultaneously with a motor task is not well understood. We showed that handgrip force steadiness and vascular control were reduced in the presence of a stressful cognitive task, particularly at a very low contraction intensity, in males and females. Motor performance and mechanisms involved under this combined demand can differ from a task performed in isolation.
Reorganization of fractal gait dynamics by auditory cueing with scale-dependent control.
Hirata K, Rouhani H, Marshall T … +4 more , Abe MO, Nakazawa K, Nozaki D, Masani K
J Appl Physiol (1985) · 2026 May · PMID 41979889 · Publisher ↗
Fractal dynamics characterize healthy human gait, with stride-interval fluctuations exhibiting long-range correlations generated by intrinsic locomotor control. These correlations diminish when gait is synchronized to an...
Fractal dynamics characterize healthy human gait, with stride-interval fluctuations exhibiting long-range correlations generated by intrinsic locomotor control. These correlations diminish when gait is synchronized to an external metronome, often accompanied by curvature in detrended fluctuation analysis (DFA) scaling, but whether this reflects suppression of intrinsic structure or a scale-dependent reorganization of control remains unclear. Here, we identified a delayed-correction mechanism capable of reproducing the characteristic curvature of DFA scaling during metronome walking. We reanalyzed treadmill data from 12 healthy men (1.1 m/s, 20 min) under free walking (FW) and metronome walking (MW). Stride intervals were extracted from foot-switch measurements and evaluated using DFA. As expected, FW showed a near-linear DFA profile, whereas MW exhibited pronounced curvature, indicating reorganization of temporal structure across scales. To test the control structure underlying this curvature, we constructed difference series from FW stride intervals and compared their DFA profiles with those of MW. Guided by simulation results predicting curvature emergence under delayed error correction, we systematically varied the differencing lag ( = 1-30). Both empirical and simulated analyses showed that MW-like curvature emerged when the current stride was corrected using information from approximately six earlier strides, with statistical analyses supporting an optimal range of 4-8 strides. These findings indicate that metronomic cueing does not simply eliminate fractal (long-range temporal) structure of gait but reorganizes gait dynamics through the superposition of two control processes: long-range fractal structure and a short-range, multistridedelayed error correction loop. Fractal gait dynamics diminish during metronome walking, but the underlying control framework remains unclear. We demonstrate that metronomic cueing does not abolish fractal structure of gait but reorganizes it via delayed, multistride error correction. Analysis reveals that the characteristic DFA curvature arises when stride timing errors are corrected using information from approximately six preceding strides. This supports the interpretation that delayed error correction contributes to the reorganization of gait dynamics during metronome walking.
Intra- and intersession reliability of ipsilateral motor pathway excitability measurements in male and female adults.
Zhou J, Ahtiainen JP, Piirainen JM … +3 more , Kidgell DJ, Avela J, Walker S
J Appl Physiol (1985) · 2026 May · PMID 41979887 · Publisher ↗
Examining ipsilateral motor pathways, purportedly reflecting cortico-reticulospinal excitability, has received growing attention in rehabilitation and exercise science. However, the reliability of measures used to assess...
Examining ipsilateral motor pathways, purportedly reflecting cortico-reticulospinal excitability, has received growing attention in rehabilitation and exercise science. However, the reliability of measures used to assess its excitability, such as ipsilateral motor-evoked potential (iMEP), remains largely unverified. Fifty-three participants (26 males and 27 females) completed two laboratory visits 1 wk apart. Dominant arm contralateral MEP (cMEP) and nondominant arm iMEP, along with maximal compound muscle action potential (M-max), from both m.biceps brachii were recorded. After determination of preacher curl one-repetition maximum (1-RM), participants performed four sets of five preacher curl repetitions at 30% of 1-RM, with 30 s rest between sets. Transcranial magnetic stimulation was delivered at 100% of maximum stimulator output during the concentric phase of the contraction (110° of flexion). Intraclass correlation coefficients (ICCs) for all variables indicated good-to-excellent intrasession (ICC ≥ 0.88) and intersession reliability (ICC ≥ 0.80). Notably, the ICCs for iMEP and cMEP amplitudes demonstrated excellent reliability for both intrasession (ICC ≥ 0.98) and intersession (ICC ≥ 0.91) measurements. iMEP presence was reliable (ICC = 0.87) and had similar variability as iMEP amplitude. However, ICC for iMEP/cMEP ratio (ICAR) was 0.83, and there was substantial intersession variability (coefficient of variation = 56.8%; relative standard error of measurement = 31.7%). Sex did not influence the reliability of the measures. iMEP and cMEP measured during preacher curl exhibited excellent intrasession and good-to-excellent intersession reliability in both sexes. Thus, this test is a useful tool to evaluate cortico-reticulospinal and corticospinal excitability in humans, although caution is advised if using ICAR. The cortico-reticulospinal tract is now thought to be an important regulator of voluntary force, but there is a shortage of accepted measures assessing its excitability. Here, we used transcranial magnetic stimulation to elicit ipsilateral motor-evoked potentials (iMEPs) in a large group of healthy males and females. We demonstrated good-to-excellent reproducibility across all iMEP characteristics (including latency, amplitude, and presence) in both sexes. iMEPs are, thus, a useful tool to assess cortico-reticulospinal excitability.
Hyperactive muscle mTORC1 attenuates functional adaptations to endurance training despite alterations in mitochondrial and lipid profiles.
Kalenta H, Marchant ED, Kilroe SP … +9 more , Maroto R, May JT, Bugay V, Romsdahl TB, Linares JJ, Hinojosa MR, Lai Z, Russell WK, Rasmussen BB
J Appl Physiol (1985) · 2026 May · PMID 41979886 · Full text
Mechanistic target of rapamycin complex I (mTORC1) is a key regulator of cell growth and metabolism, and its activity increases with aging. Hyperactivation of mTORC1 is associated with the pathology of sarcopenia and mit...
Mechanistic target of rapamycin complex I (mTORC1) is a key regulator of cell growth and metabolism, and its activity increases with aging. Hyperactivation of mTORC1 is associated with the pathology of sarcopenia and mitochondrial dysfunction. Exercise training has been shown to improve muscle quality and function in people with sarcopenia. However, it is unknown if hyperactive mTORC1 will alter exercise training-induced adaptations. In this study, we examined the effect of endurance training on muscle function and metabolism in a mouse model of hyperactive mTORC1 [DEP domain-containing protein 5 muscle-specific knockout (DEPDC5 mKO)]. After 8 wk of exercise training, DEPDC5 mKO mice had increased mitochondrial activity and tibialis anterior (TA) muscle mass, despite no change in physical function. Furthermore, DEPDC5 mKO mice had a trend for reduction in the phosphorylation of the mTORC1 downstream target, ribosomal protein S6, which may have contributed to the lack of functional adaptations. In addition, there was a reduction in triglycerides (TGs) and phosphatidylcholines (PCs) in DEPDC5 mKO mice, suggesting an increase in lipid fuel use and alterations in lipid membrane composition due to an increase in mitochondrial activity. We conclude that hyperactive mTORC1 in muscle may attenuate functional adaptations to endurance exercise training, despite increasing mitochondrial respiration and alterations in lipid metabolism. Endurance exercise training in mice with hyperactive muscle mechanistic target of rapamycin complex I (mTORC1) was associated with increase in mitochondrial activity and TA muscle mass despite lack of changes in physical function. These findings could be attributed to altered autophagy-related signaling and a reduction in the phosphorylation of ribosomal protein S6, downstream target of mTORC1, after exercise training in DEPDC5 mKO mice. Reduction in phosphatidylcholines (PCs) and triglycerides (TGs) may suggest an increase in lipid fuel use and alterations in lipid membrane composition due to an increase in mitochondrial activity.
Ketone monoester reduces blood glucose, exogenous CHO oxidation, and oxidation efficiency in trained male cyclists when fed 120 g/h of CHO during exercise.
Martyn HJ, Cameron NE, Edmondson JA … +6 more , Phelan MM, Gonzalez JT, Shepherd SO, Pugh JN, Owens DJ, Morton JP
J Appl Physiol (1985) · 2026 May · PMID 41962970 · Publisher ↗
We examined the effects of ketone monoester (KME) and carbohydrate (CHO) coingestion on exogenous CHO oxidation (via U-C-enriched glucose-fructose drinks), metabolomic responses, and exercise capacity. In a randomized cr...
We examined the effects of ketone monoester (KME) and carbohydrate (CHO) coingestion on exogenous CHO oxidation (via U-C-enriched glucose-fructose drinks), metabolomic responses, and exercise capacity. In a randomized crossover design (after 36 h of CHO loading and pre-exercise meal of 12 and 2 g·kg, respectively), eight trained male cyclists (V̇o; 66 ± 7 mL·kg·min) ingested 0 g·h (PLA), 120 g·h CHO (CHO), or 120 g·h CHO + 75-g ketone monoester (CHO + KME) during 3 h of cycling at power outputs corresponding to 95% of lactate threshold (LT) followed by exercise to exhaustion at 150% LT. Mean blood glucose concentrations during exercise were different between all pairwise comparisons ( < 0.05) such that CHO > CHO + KME > PLA (4.9 ± 0.3, 4.4 ± 0.2, 3.7 ± 0.4 mmol·L, respectively). Mean exogenous CHO oxidation (1.35 ± 0.15 vs. 1.50 ± 0.16 g·min, < 0.01) and oxidation efficiency was lower in CHO + KME (67 ± 7%) compared with CHO (75 ± 6%, < 0.01). Exercise capacity was greater ( < 0.05) in CHO (349 ± 189 s) and CHO + KME (319 ± 225 s) compared with PLA (75 ± 105 s), though no differences were evident between CHO and CHO + KME ( > 0.05). Ketone monoester ingestion increased abundance of metabolites associated with carbohydrate metabolism (glucaric acid) and protein turnover (3-methylhistidine). We conclude that ketone monoester ingestion does not enhance exercise capacity and reduces blood glucose concentrations, exogenous CHO oxidation, and oxidation efficiency when compared with CHO alone. To promote exercise performance, endurance athletes frequently consume CHO during exercise at ingestion rates of 90-120 g·h. Here, we report for the first time that coingestion of a ketone monoester before and during prolonged cycling reduces blood glucose concentrations, exogenous CHO oxidation, and oxidation efficiency compared with CHO alone (120 g·h; 1:0.8 ratio of maltodextrin and fructose). Ketone monoester ingestion also increased plasma abundance of metabolites associated with carbohydrate metabolism (glucaric acid) and protein turnover (3-methylhistidine).
Initial contractions of a single-load fatiguing exercise provide a valid assessment of age-related differences in peak power.
Wrucke DJ, Colosio M, James JJ … +2 more , Hunter SK, Sundberg CW
J Appl Physiol (1985) · 2026 May · PMID 41956706 · Full text
The "gold standard" for measuring peak muscle power outputs is a comprehensive torque-velocity assessment performed across a wide range of loads and contraction velocities. However, this approach requires multiple high-l...
The "gold standard" for measuring peak muscle power outputs is a comprehensive torque-velocity assessment performed across a wide range of loads and contraction velocities. However, this approach requires multiple high-load efforts that place stress on the joints, is time-intensive, and is often impractical in large cohorts or in clinical populations such as very old adults. Furthermore, it remains unclear whether simplified protocols underestimate age- and sex-related differences in peak power. We compared peak knee extensor power derived from a torque-velocity assessment with that obtained from the initial 10 contractions of a single-load fatiguing task in young, old, and very old males and females. Thirty young (22.6 ± 2.2 yr, 15 females), 73 old (70.6 ± 4.7 yr, 33 females), and 16 very old adults (85.8 ± 4.2 yr, 9 females) completed a torque-velocity assessment (14 isokinetic velocities, 30-450°·s) and a 4-min dynamic fatiguing exercise task (1 isotonic load at 20% of maximal voluntary isometric contraction, 80 contractions). Peak power outputs were strongly correlated between protocols ( < 0.001, = 0.962), and the estimated age-related declines in power did not differ between the torque-velocity and fatigue task in males (∼6.6 W·yr vs. ∼6.5 W·yr, = 0.639) or females (∼4.3 W·yr vs. ∼4.2 W·yr, = 0.736). Peak power outputs from the initial 10 contractions of the fatigue task were ∼13% lower compared with the torque-velocity assessment ( < 0.001). These findings indicate that a brief fatiguing exercise task provides a valid alternative to the torque-velocity assessment for determining peak power across age groups, while simultaneously measuring fatigability, a clinically and physiologically important neuromuscular characteristic. The initial contractions of a single-load fatiguing exercise can determine peak power outputs, showing a strong correlation ( = 0.962) with a comprehensive isokinetic torque-velocity assessment in young, old, and very old males and females. This approach accurately captures the age-related differences in peak power while simultaneously quantifying fatigability. Although peak power is underestimated by ∼13% compared with the torque-velocity assessment, the approach offers a practical way to evaluate two important neuromuscular outcomes in a single task.
Primary cilia mediate stress vulnerability and exercise-induced antidepressant adaptation: evidence for ventral hippocampal astrocytic ciliary remodeling.
Hwang DJ, Cho JY
J Appl Physiol (1985) · 2026 May · PMID 41956699 · Publisher ↗
Chronic stress engenders marked interindividual heterogeneity in vulnerability to depression and anxiety, indicating that distinct neurobiological processes shape susceptibility and resilience. To identify the mechanisms...
Chronic stress engenders marked interindividual heterogeneity in vulnerability to depression and anxiety, indicating that distinct neurobiological processes shape susceptibility and resilience. To identify the mechanisms underlying this divergence, male C57BL/6J mice subjected to chronic restraint stress were stratified into stress-susceptible or resilient phenotypes using multidimensional behavioral clustering. To examine how exercise modifies these stress-defined endophenotypes, we used a graded treadmill paradigm in which low-, moderate-, and high-intensity exercises were parametrically defined relative to the ventilatory threshold (VT). Only low-intensity exercise performed below VT produced robust antidepressant and anxiolytic effects in susceptible mice. Whole-brain c-Fos mapping revealed the selective recruitment of the ventral hippocampus (vHPC) during low-intensity exercise. Chemogenetic silencing of vHPC neurons abolished these behavioral benefits, indicating that vHPC engagement is essential for exercise-induced resilience. Transcriptomic profiling of vHPC showed that this adaptive state was associated with the coordinated modulation of primary cilium-associated gene networks. Morphometric analyses confirmed that chronic stress-induced pronounced elongation of primary cilia, particularly in astrocytes, whereas low-intensity exercise restored both ciliary length and the proportion of ciliated astrocytes. These structural recalibrations coincided with reduced expression of proinflammatory cytokines, including IL-1α and fractalkine, suggesting that astrocytic cilia act as a key interface linking stress signaling to neuroimmune regulation. Collectively, these findings outline a mechanistic cascade in which exercise below the VT engages vHPC circuits, reorganizes cilia-related transcriptional programs, and restores astrocyte and inflammatory homeostasis, converting stress-susceptible states into resilient phenotypes. Chronic stress produced distinct stress-susceptible and stress-resilient phenotypes in mice. Exercise intensity was critical: low-intensity running below the ventilatory threshold alleviated depression- and anxiety-like behaviors and normalized basal corticosterone levels. These benefits required ventral hippocampal activity, as chemogenetic silencing blunted the behavioral rescue. Stress susceptibility was associated with elongation and increased prevalence of astrocytic primary cilia in the vHPC, which were reversed by low-intensity exercise, accompanied by transcriptomic reprogramming and alteration in proinflammatory cytokine expression.
Operating lung volume and perceived dyspnea during progressive hypercapnia: the effect of biological sex.
Adibmoradi G, Shekarloo P, Darko CA … +4 more , Jamal-Zadeh P, Sadeghi A, Edgell H, Phillips DB
J Appl Physiol (1985) · 2026 May · PMID 41934503 · Publisher ↗
Females often report greater breathing discomfort and unpleasantness than males during exercise, secondary to a greater respiratory mechanical load for a given level of ventilation. However, sex differences in breathing...
Females often report greater breathing discomfort and unpleasantness than males during exercise, secondary to a greater respiratory mechanical load for a given level of ventilation. However, sex differences in breathing discomfort/unpleasantness and the relative influence of respiratory mechanics during hypercapnia (increased arterial CO tension) are poorly understood. We compared ventilatory and perceptual parameters during progressive hypercapnia in young healthy females and males. We hypothesized that heightened dyspnea during hypercapnia in females would be associated with greater mechanical loads, compared with males. Fifteen healthy young females and 15 age-matched males completed lung function testing, followed by a modified Duffin CO rebreathing test. Pulmonary ventilation, breathing pattern, partial pressure of end-tidal CO ([Formula: see text]), operating lung volumes (to estimate respiratory mechanical load), and perceived breathing discomfort and unpleasantness (modified Borg 0-10 scale) were acquired throughout CO rebreathing. Linear mixed modeling was used to determine between-sex differences in ventilatory and perceptual parameters throughout CO rebreathing. Pulmonary ventilation and tidal volume were lower, and end-inspiratory lung volume (EILV), perceived breathing discomfort, and unpleasantness were greater in females than males during hypercapnia (all < 0.05). The rise in breathing discomfort/unpleasantness ratings relative to pulmonary ventilation was greater in females than in males (both < 0.05). When accounting for the magnitude of between-group differences in EILV during hypercapnia, breathing discomfort and unpleasantness were similar between the sexes. These data suggest that the heightened perceptual consequence of greater EILV reflects an increased awareness of higher inspiratory mechanical loads during hypercapnia in females. Despite past findings providing mechanistic insights into biological sex differences in dyspnea sensation during exercise, it remains unclear how biological sex differences in respiratory/structure function regulate the perception of dyspnea during progressive hypercapnia. Our results show that females report greater perceived breathing discomfort and unpleasantness than males during progressive hypercapnia. When accounting for the magnitude of between-group differences in end-inspiratory lung volume during hypercapnia, breathing discomfort and unpleasantness were similar between the sexes.
Exogenous ketosis does not alter oxygenation, oxygen uptake kinetics, or whole-body efficiency during submaximal exercise in early high-altitude acclimatization.
Tominec D, Stalmans M, Narang BJ … +3 more , Millet GP, Poffé C, Debevec T
J Appl Physiol (1985) · 2026 May · PMID 41934484 · Publisher ↗
Exogenous ketosis, induced via ketone monoester (KE) ingestion, has been shown to attenuate hypoxia-induced blood, muscle, and brain deoxygenation and augment oxygen uptake (V̇o) under acute normobaric hypoxia. However,...
Exogenous ketosis, induced via ketone monoester (KE) ingestion, has been shown to attenuate hypoxia-induced blood, muscle, and brain deoxygenation and augment oxygen uptake (V̇o) under acute normobaric hypoxia. However, its effects on exercise responses during early acclimatization at terrestrial high-altitude remain unexplored. Thirty-four healthy, active adults completed four exercise sessions: one near sea level and then once per day during a 3 day altitude sojourn (3,375 m), with regular KE or placebo ingestion. Pulmonary gas exchange, minute ventilation, cardiac output, pulse oxygen saturation, skeletal muscle tissue saturation index (TSI), and brain TSI were measured during moderate- and heavy-intensity exercise. KE ingestion induced ketosis at the start of each exercise session (group × time interaction: < 0.001). However, compared with placebo, KE resulted in a comparable (group × time interaction: = 0.501) high-altitude-induced slowing of the primary phase time constant of V̇o kinetics during heavy-intensity exercise (time effect: < 0.001). Moreover, both groups exhibited similar (all group × time interactions: > 0.123) hypoxia-related decreases in gas exchange and increases in minute ventilation, accompanied by reductions in pulse oxygen saturation and brain TSI during both moderate- and heavy-intensity exercise across the 3 days (all time effects: < 0.015). Notably, KE ingestion increased cardiac output during moderate-intensity exercise on the first altitude day (group × time interaction: = 0.042). Whole-body energy efficiency was preserved across time at 3,375 m (time effect: = 0.060) in both groups (group × time interaction: = 0.084). These data indicate that intermittent exogenous ketosis does not attenuate altitude-induced alternations in V̇o kinetics or tissue oxygenation, nor improves whole-body efficiency, during moderate- or heavy-intensity exercise across 3 days at 3,375 m. This study demonstrates that intermittent exogenous ketosis does not alter the high-altitude slowing of the primary phase of V̇o kinetics during the transition to heavy-intensity exercise, nor does it change ventilatory, gas exchange, blood or tissue oxygenation responses, or whole-body efficiency across 3 days at 3,375 m. However, preexercise ketone monoester ingestion increased cardiac output during moderate-intensity exercise on arrival to 3,375 m and after 24 h, but this did not translate to broader physiological benefits.
Sex-specific differences in lung mitochondrial function and injury in rats exposed to hyperoxia.
Taheri P, Taye AG, Dave D … +5 more , Jacobs ER, Sharma GP, Clough AV, Dash RK, Audi SH
J Appl Physiol (1985) · 2026 May · PMID 41934471 · Full text
Hyperoxia is both an essential therapy and a contributor to lung injury in acute respiratory distress syndrome. We hypothesized that adult female rats are relatively protected from hyperoxia-induced acute lung injury (HA...
Hyperoxia is both an essential therapy and a contributor to lung injury in acute respiratory distress syndrome. We hypothesized that adult female rats are relatively protected from hyperoxia-induced acute lung injury (HALI) compared with males and that this protection is associated with sex-dependent differences in lung mitochondrial bioenergetics and HO production. Adult rats were exposed to room air (normoxia) or hyperoxia (>95% O) for up to 60 h. Lung injury was assessed by pleural effusion, lung wet weight, pulmonary vascular filtration coefficient (), histologic injury scores, and cleaved caspase-3 (CC3) staining. Expression of mitochondrial - was quantified in lung tissue. Mitochondrial oxygen consumption rates (OCRs) and HO (mtHO) production were measured in isolated lung mitochondria, and lung HO release rate was quantified in isolated perfused lungs. Hyperoxia caused systemic and pulmonary injury in both sexes. However, compared with females, males showed greater body weight loss and larger increases in lung wet weight, pleural effusion, , and CC3-positive cells. Hyperoxia decreased expression in males but not females and impaired OCRs in both sexes. For both sexes, was the dominant mtHO source. Hyperoxia nearly doubled mtHO production in female, but not male, mitochondria. Nevertheless, whole lung HO release rate in females did not increase, consistent with enhanced tissue-level scavenging. These findings indicate attenuated severity of HALI in adult females, highlight as a major mtHO source during hyperoxia, and support consideration of sex as a biological variable in mitochondria-targeted therapies for HALI. We investigated sex-specific responses to hyperoxia-induced acute lung injury (HALI) in rats. Female rats exhibited attenuated severity, with less pleural effusion, pulmonary edema, and apoptosis than males. Studies in isolated mitochondria, lung tissue homogenates, and isolated lungs indicate that this attenuated severity is associated with mitochondrial adaptations and enhanced tissue HO scavenging capacity. These findings underscore the importance of sex as a biological variable and identify mitochondrial as a potential HALI therapeutic target.
Heat training augments hemoglobin mass during a moderate-altitude training camp in well-trained endurance athletes.
Rønnestad BR, Urianstad Odden T, Blindheim PM … +5 more , Hansen J, Hamarsland H, Ellefsen S, Urianstad Odden I, Mølmen KS
J Appl Physiol (1985) · 2026 May · PMID 41934470 · Publisher ↗
Altitude training is a well-established method for increasing hemoglobin mass (Hb) in endurance athletes, with altitudes >2,300-2,500 m above sea level (m.a.s.l.) commonly used to promote such adaptations. However, logis...
Altitude training is a well-established method for increasing hemoglobin mass (Hb) in endurance athletes, with altitudes >2,300-2,500 m above sea level (m.a.s.l.) commonly used to promote such adaptations. However, logistical constraints, including limited access to sport-specific facilities (e.g., shooting ranges for biathletes), may limit its use. Therefore, this study investigated whether adding heat training to a camp conducted at moderate natural altitude (1,865 m.a.s.l.) could enhance hematological adaptations. Forty-six well-trained cross-country skiers and biathletes [F, 20; M, 26; maximal oxygen uptake, 69.1 (8.2) mL·min·kg] were assigned to one of three groups for a 3 wk intervention: ) residing and training at moderate altitude with three weekly heat-suit cycling sessions (MOD-ALT), ) residing and training at moderate altitude (MOD-ALT), or ) residing and training at sea level (CON). Hematological variables and roller-ski performance were assessed before and after the intervention. MOD-ALT demonstrated a greater increase in Hb (2.9%) compared with both MOD-ALT (1.2%, = 0.017) and CON (-0.2%, < 0.001). The greater Hb increase was accompanied by a larger increase in red blood cell volume. No significant difference in Hb change was observed between MOD-ALT and CON, and no between-group differences were found in submaximal or maximal performance measures. These findings suggest that including three weekly heat-suit cycling sessions to a moderate-altitude training camp enhances hematological adaptations compared with moderate altitude or sea level training alone, although no significant between-group differences were observed in roller-skiing performance indicators. This strategy may offer a practical and effective alternative for athletes and coaches when access to higher altitude training environments is limited. Adding three weekly heat training sessions to a training camp at moderate natural altitude (<2,000 m.a.s.l.) resulted in greater increase in hemoglobin mass compared with traditional training at moderate altitude or sea level in well-trained endurance athletes. However, these hematological improvements were not accompanied by significant between-group differences in submaximal or maximal roller-ski performance indicators. Heat training may represent a practical strategy for coaches and athletes to enhance erythropoietic adaptations when higher-altitude environments are unavailable.
Acute stress induces coordinated reorganization across interacting brain networks.
Braun J, Patel M, Woods W … +3 more , Keatch C, Lambert E, Kameneva T
J Appl Physiol (1985) · 2026 May · PMID 41931582 · Publisher ↗
Stress initiates alterations in electrophysiological brain activity that are correlated with increases in muscle sympathetic nerve activity (MSNA), heart rate (HR), and blood pressure (BP). However, we do not know if cha...
Stress initiates alterations in electrophysiological brain activity that are correlated with increases in muscle sympathetic nerve activity (MSNA), heart rate (HR), and blood pressure (BP). However, we do not know if changes in brain activity occur solely in regions comprising the central autonomic network, or if other large-scale brain networks are involved in the stress-induced pressor response. To answer this question, this study measured connectivity between different brain regions at rest and during acute stress, using magnetoencephalography in 29 healthy individuals. Whole head and regions of interest analyses were performed using phase-lag indices as a connectivity metric. Regions of interest were confined to the central autonomic, sensorimotor, salience, default, and central executive networks. Functional connectivity was calculated on magnetoencephalography recordings that were filtered into delta (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz), low gamma (30-80 Hz), and high gamma (80-120 Hz) bands. Substantial reductions in connectivity were observed during cognitive stress. These were largely characterized by reduced parahippocampal-sensorimotor connectivity in beta and high gamma bands. Moreover, reduced connectivity within the central autonomic, sensorimotor, and default mode networks was noted, specifically as a reduction in the alpha band between the precuneus and hippocampus. We observed a salience-directed switching between the default and executive networks, driven by reduced right anterior cingulate-right insula connectivity. Furthermore, we observed reduced right medial prefrontal cortex-brainstem connectivity in beta band. Our results indicate that stress influences the functional connectivity of several key brain regions that interact with multiple large-scale brain networks linked to mental and physical states. This study reveals significant reductions in functional connectivity among several large-scale brain networks during stress. Reduced connectivity was observed within central autonomic, sensorimotor, default, salience, and executive networks in alpha (8-13 Hz), beta (13-30 Hz), and high gamma (80-120) bands, including reduced connectivity between the right medial prefrontal cortex and the brainstem.
Impeding respiratory venous return fluctuations alters cardiorespiratory autonomic and mechanical interactions.
Skytioti M, Holme NL, Zilakos I … +2 more , Søvik S, Elstad M
J Appl Physiol (1985) · 2026 May · PMID 41931555 · Publisher ↗
Cardiorespiratory interactions are important for circulatory control. The act of breathing modulates cardiac output. To explore underlying mechanisms, we investigated cardiovascular responses to respiration-synchronous i...
Cardiorespiratory interactions are important for circulatory control. The act of breathing modulates cardiac output. To explore underlying mechanisms, we investigated cardiovascular responses to respiration-synchronous intermittent hypovolemia. Twelve healthy subjects underwent metronome-paced breathing synchronized with oscillatory lower body negative pressure (LBNP, 0 to -30 mmHg). Oscillations were timed to either ) induce LBNP on inspiration (Insp + LBNP), reducing venous return and impeding mechanical effects of breathing on circulation, or ) release LBNP on inspiration (Exp + LBNP), augmenting mechanical effects of breathing through augmented venous return fluctuations. We recorded heart rate (HR, from ECG), noninvasive finger arterial blood pressure, and estimated left cardiac stroke volume by ultrasound Doppler (l-SV). We quantified each cardiovascular variable's respiratory-related variability by spectral analysis at peak respiratory frequency ±0.03 Hz and calculated coherence and phase angles by cross-spectral analysis. Differences between LBNP situations were tested by Wilcoxon paired signed rank test. Oscillatory LBNP elicited different responses depending on the timing of onset and release within the respiratory cycle. Variability in MAP increased fivefold during Insp + LBNP compared with Exp + LBNP, whereas variability in SV doubled during Exp + LBNP compared with Insp + LBNP. Variability in HR and SV showed a consistent phase with respiration, independent of LBNP onset and release. MAP showed little variability when the respiratory pump was augmented, and larger variability when normal interplay between the respiratory pump and circulation was impeded. HR variability was mainly driven by respiration, despite concomitant respiration-synchronous oscillatory central hypovolemia. Respiration may have a higher potential for autonomic enforcement during cardiovascular stress, such as hypovolemia. We used an innovative approach to modulate the effects of the respiratory pump on circulation in healthy individuals. By synchronizing lower body negative pressure with either inspiration or expiration, the respiratory pump was inhibited or augmented. The arterial blood pressure declined, and its fluctuations became pronounced when the respiratory pump was impeded, and normal cardiorespiratory interactions were disrupted. Cardiorespiratory interactions seem to supersede the strong baroreceptor stimulus generated by cyclic fluctuations in central blood volume.
Effects of glucose ingestion on blood flow in the small intestine and exercising limbs during endurance exercise.
Endo MY, Kashima H, Miura A … +1 more , Fukuba Y
J Appl Physiol (1985) · 2026 May · PMID 41926638 · Publisher ↗
Performance during endurance exercise depends on the balance between the blood flow (BF) to active muscles and their energy use. We compared the acute cardiovascular regulation after the ingestion of a 300-mL drink conta...
Performance during endurance exercise depends on the balance between the blood flow (BF) to active muscles and their energy use. We compared the acute cardiovascular regulation after the ingestion of a 300-mL drink containing 50 g glucose (G trial) or not (water, W trial) during the ninth minute of 40 min of bilateral knee extension exercise in 12 healthy participants. The blood pressure, heart rate, cardiac output, gas exchange variables, and BF through the superior mesenteric (SMA), femoral (FA), and brachial (BA) arteries and skin in the forearm and chest were measured continuously. Regional vascular conductance (VC) was calculated as BF/mean arterial pressure. BF significantly decreased after glucose ingestion, but did not change after water ingestion. BF significantly increased from 15 min after glucose ingestion to the end of protocol, but did not change after water ingestion. BF through the BA and forearm and chest skin during the G and W trials significantly increased after drink ingestion and did not significantly differ between the trials. Temporal changes in the VC of the FA, SMA, BA, and skin of the forearm and chest mirrored the BF responses in each vessel. The central hemodynamic variables, V̇o, and V̇co responses did not significantly differ between the G and W trials. These findings imply that the cardiovascular responses to glucose ingestion during exercise involve the redistribution of some of the BF in the active limbs to the small intestine for digestion and absorption, but no additional increase in cardiac output. This study is the first to comprehensively assess regional blood flow (BF) responses to glucose ingestion during exercise. We demonstrate that glucose intake during high-intensity exercise increases intestinal BF, while reducing the flow to active limbs, without changes in cardiac output. These findings imply that there is a competition between digestion and working limbs for limited circulatory resources, and provide novel insight into how carbohydrate intake affects BF distribution and energy delivery during endurance exercise.
Fluid balance, kidney function, and acute kidney injury risk in healthy men and women during simulated work-related heat stress.
Freemas JA, Goss CS, Ables R … +9 more , Baker TB, Bruinvels G, Mündel T, Martin BJ, Carter SJ, Chapman RF, Khandpekar OM, Zoh RS, Schlader ZJ
J Appl Physiol (1985) · 2026 May · PMID 41914660 · Full text
We tested the hypothesis that men are at greater risk of dehydration during simulated work-related heat stress (WrHS) compared with women independent of menstrual cycle phase. Twelve eumenorrheic women completed a WrHS s...
We tested the hypothesis that men are at greater risk of dehydration during simulated work-related heat stress (WrHS) compared with women independent of menstrual cycle phase. Twelve eumenorrheic women completed a WrHS simulation during the early follicular (EF), late follicular (LF), and midluteal (ML) phase of their menstrual cycle and 12 men completed one WrHS simulation. The WrHS simulation involved a 4-h exposure to 33.8 ± 0.8°C, 54 ± 1% relative humidity, where participants walked on a treadmill for 30 min per hour at a rate of metabolic heat production of 5.2 ± 0.7 W/kg (199 ± 28 W/m). Participants drank a cool noncaloric sport drink ad libitum. Percent changes in nude body weight from pre- to post-WrHS did not differ between men (-0.5 ± 0.5%) and women (EF: -0.5 ± 0.9%; LF: -0.3 ± 0.9%; ML: -0.3 ± 0.7%) during any phase of the menstrual cycle ( ≥ 0.4694). Relative fluid intake was higher in women during LF [43 ± 18 mL/kg lean body mass (LBM); = 0.0148] and ML (43 ± 16 mL/kg LBM; = 0.0048), but not EF (36 ± 21 mL/kg LBM; = 0.1792) compared with men (24 ± 5 mL/kg LBM). Relative urine output was higher in women (20 ± 12 mL/kg LBM) compared with men (8 ± 4 mL/kg LBM) across menstrual cycle phases ( ≤ 0.0367). Relative total sweat loss did not differ between men [700 ± 160 mL/m body surface area (BSA)] and women (675 ± 254 mL/m BSA) during any phase of the menstrual cycle ( ≥ 0.8458). Although the way it was achieved differed, when cool fluids are available, fluid balance is similarly achieved in men and women independent of the menstrual cycle, suggesting that the risk of dehydration during WrHS is not modified by biological sex. Although men are often thought to be at greater risk of dehydration during work-related heat stress due to lower fluid intake, the impact of biological sex on fluid balance remains unclear. This study shows that when cool fluids are available, men and women maintain similar fluid balance regardless of menstrual cycle phase, suggesting that sex does not influence dehydration risk during simulated work-related heat stress.
The effect of nasal patency and anatomy during asymmetrical nasal high flow.
Rees M, Vieira F, Yarragudi SB … +2 more , Barnes M, Tatkov S
J Appl Physiol (1985) · 2026 May · PMID 41903146 · Publisher ↗
Nasal high flow (NHF) with the asymmetrical cannula interface (AI) is increasingly used as respiratory support across a broad range of patients. By incorporating one unilaterally oversized prong, the AI enhances dead-spa...
Nasal high flow (NHF) with the asymmetrical cannula interface (AI) is increasingly used as respiratory support across a broad range of patients. By incorporating one unilaterally oversized prong, the AI enhances dead-space clearance and increases airway pressure. This study investigated the effects of nasal patency and anatomical variability of the upper airways during NHF delivered with the AI. Twenty healthy adults underwent three 3-h study periods, whereby heated, humidified air was delivered at 30 L/min via either an AI, a symmetrical interface (SI), or a control condition without NHF. Nasal patency was assessed every 30 min using acoustic rhinometry, rhinomanometry, and a self-assessment questionnaire. Measurements were quantified using a laterality index, and ventilation was monitored by respiratory inductance plethysmography. Nasal anatomy was evaluated using magnetic resonance imaging, and airway replicas reconstructed from these images, including original and mirrored models, were tested in bench-top experiments. All measures of nasal patency were significantly positively correlated ( < 0.001). There was no association between the AI laterality index and respiratory rate or tidal volume. In the three-dimensional models, both airway pressure and dead-space clearance increased when the leak area was reduced by changing the SI to the AI. Compared with the originals, mirroring the nasal passages showed no difference except for the model with severe nasal septum deviation. NHF with SI or AI did not alter the dominant side of nasal patency, which did not affect ventilation. Nares morphology, rather than physiological alternation in nasal patency, may have a greater influence on pressure generation during NHF. The asymmetrical cannula interface used during nasal high flow (NHF) causes unequal occlusion of the nares. This study demonstrates that physiological changes of nasal patency at the internal nasal valve, known as the nasal cycle, do not affect ventilation during NHF. In contrast, anatomical variability, such as differences in the cross-sectional area of the nares or severe nasal septum deviation, may substantially influence the generated pressure and could produce physiologically relevant effects during therapy.
Resting physiological and perceptual responses to nasal high-flow O therapy in naïve patients with fibrotic interstitial lung disease.
Thivent S, Ginoux M, Verges S … +2 more , Hérengt F, Marillier M
J Appl Physiol (1985) · 2026 Apr · PMID 41886313 · Publisher ↗
Fibrotic interstitial lung disease (-ILD) is characterized by impaired pulmonary gas exchange, increased ventilatory demand, and disabling dyspnea. Conventional O therapy at rest improves patients' oxygenation but not ve...
Fibrotic interstitial lung disease (-ILD) is characterized by impaired pulmonary gas exchange, increased ventilatory demand, and disabling dyspnea. Conventional O therapy at rest improves patients' oxygenation but not ventilatory requirements. Nasal high flow (NHF) with or without supplemental O may reduce ventilatory demand, but its acute physiological and perceptual benefits remain unclear in -ILD. Fifteen naïve patients (partial pressure of arterial O = 57 ± 12 mmHg) underwent, in a randomized, single-blind, cross-over trial, six bouts of 7-min exposure: room air; conventional O [fraction of inspired O ([Formula: see text]) = 0.5 or 1.0]; nasal high-flow without O-enriched air (NHF; 30 L·min, [Formula: see text] = 0.21); and nasal high-flow O ([Formula: see text]; 30 L·min, [Formula: see text] = 0.3 or 0.5). Breathing pattern (respiratory plethysmography), O saturation ([Formula: see text]), dyspnea intensity (Borg CR-10), and qualitative descriptors were compared across conditions. [Formula: see text] improved in O-enriched conditions (≥98%) versus air and NHF (∼92%; < 0.001). NHF and [Formula: see text] with [Formula: see text] = 0.3 and [Formula: see text] = 0.5 lessened ventilation versus room air (7.8 ± 3.0, 7.1 ± 3.3, 7.0 ± 2.5, and 9.3 ± 3.0 L·min, respectively; all ≤ 0.044), but conventional O had no significant effect. Respiratory rate only decreased with [Formula: see text] with [Formula: see text] = 0.3 versus air (20 ± 6 vs. 23 ± 5 breaths·min; = 0.008). Dyspnea intensity was greater with NHF modalities versus conventional O (∼1 Borg unit; all ≤ 0.030); qualitative descriptors did not differ across conditions. In moderately hypoxemic patients with -ILD, NHF (regardless of O enrichment) but not conventional O therapy lessened resting ventilatory requirements. Concurrently, NHF increased dyspnea intensity despite preserved qualitative dimensions, suggesting dissociation between physiological and perceptual responses in this population. These findings highlight the need for individualized strategies when implementing [Formula: see text] in naïve patients with -ILD. In moderately hypoxemic, naive individuals with fibrotic interstitial lung disease, nasal high flow (regardless of O enrichment) lessened resting ventilatory requirements versus room air but increased dyspnea intensity versus conventional O therapy, suggesting dissociation between physiological and perceptual responses in this population. Our findings thus highlight the need for individualized strategies when implementing nasal high flow O therapy in these patients.
Characterizing motor unit firing rates in the human erector spinae.
Travis PJ, Fanous J, Rice CL
J Appl Physiol (1985) · 2026 May · PMID 41886304 · Publisher ↗
Muscles of the erector spinae (ES) are vital for maintaining posture, yet their motor unit firing rates (MUFRs) are not well described compared with many limb muscles. Therefore, this study aimed to characterize ES MUFRs...
Muscles of the erector spinae (ES) are vital for maintaining posture, yet their motor unit firing rates (MUFRs) are not well described compared with many limb muscles. Therefore, this study aimed to characterize ES MUFRs across a full range of contractile intensities, including at maximum voluntary contraction (MVC). Intramuscular electromyography was used to record motor unit activity from the ES muscles (left and right sides) in 10 healthy participants. Data were collected during isometric trunk extension at intensities from 10% to 100% MVC. Voluntary activation was assessed using transcranial magnetic stimulation, and mean values were >88%. Torque-firing rate relationships were analyzed to identify rate-coding patterns and potential side-to-side differences at each intensity. Contrary to our hypothesis, the ES exhibited rate-coding patterns similar to limb muscles reported previously. A linear relationship was observed between torque and MUFR, with mean rates increasing from ∼10 Hz at 10% MVC to ∼34 Hz at 100% MVC. A significant side-related effect was found at higher intensities, in which the nondominant side demonstrated higher MUFRs compared with the dominant side. These findings indicate that whereas the ES serves a unique postural role, rate-coding strategies are comparable to those of the appendicular musculature. The observed side-to-side differences at high intensities may reflect functional asymmetries in trunk stabilization. This study provides a comprehensive characterization of the human erector spinae motor unit firing rates across a full range of intensities, including maximal effort with assessment of voluntary activation during isometric back extensions. Contrary to neural circuitry differences and postural function, the erector spinae rate codes similar to limb muscles. Furthermore, we identified significant side-to-side differences in firing rates at higher intensities, indicating a neural compensation to maintain spinal stability.
Muscle atrophy after ACL reconstruction involves molecular mechanisms beyond unloading.
Keeble AR, Gonzalez-Velez S, Thomas NT … +10 more , Owen AM, Stone AV, Johnson DL, Candia J, Ferrucci L, Narici M, Dupont-Versteegden EE, Noehren B, Franchi MV, Fry CS
J Appl Physiol (1985) · 2026 Apr · PMID 41886295 · Full text
Anterior cruciate ligament reconstruction (ACLR) leads to profound muscle atrophy and weakness that remain resistant to rehabilitation. Although early recovery typically involves a brief period of limb unloading, the deg...
Anterior cruciate ligament reconstruction (ACLR) leads to profound muscle atrophy and weakness that remain resistant to rehabilitation. Although early recovery typically involves a brief period of limb unloading, the degree to which disuse alone accounts for muscle pathology after ACLR remains unclear. Here, we leveraged publicly available RNA-seq datasets of muscle biopsies from vastus lateralis obtained 7 days after ACLR or 10 days after unilateral lower limb suspension (ULLS), each with matched control limbs, to directly compare disuse-driven and ACLR-specific early transcriptional responses. Despite similar periods of reduced loading, substantial transcriptomic divergence was identified using both intersection and interaction bioinformatic analyses. Only 16% of differentially expressed genes (DEGs) were common to both ACLR and ULLS, with ACLR eliciting over 1,000 more DEGs than ULLS. ACLR was characterized by reduced extracellular matrix (ECM) remodeling and robust induction of denervation-responsive genes, which were not observed with unloading alone. These findings indicate that unloading contributes only modestly to the early muscle transcriptomic response following ACLR. Identifying potential ACLR-specific molecular effectors of atrophy advances our understanding of its unique pathophysiology that may underlie poorer functional recovery. Disuse is often suggested as a major driver of quadriceps pathology following anterior cruciate ligament reconstruction (ACLR). This study identifies shared and unique gene signatures that occur early with ACLR and unilateral lower limb suspension (ULLS), highlighting ACLR-specific responses that likely contribute to prolonged quadriceps atrophy and weakness.
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