J. Appl. Physiol. [JOURNAL]
Sun
200 papers
Exercise FITT-V during pregnancy: dose-dependent reduction in infant cellular lipid content and whole body fat.
Claiborne A, Jevtovic F, Biagioni EM … +13 more , Rossa L, Ollmann C, Zheng D, Strom C, Wisseman B, McDonald S, Newton E, Mouro S, deVente J, Kelley GA, Houmard JA, Broskey NT, May LE
J Appl Physiol (1985) · 2026 Mar · PMID 41665099 · Full text
Modifiable health behaviors such as exercise regulate adiposity in adults, but the effects of exercise during pregnancy on infant adiposity remain understudied. This report analyzed the relationship between prenatal exer...
Modifiable health behaviors such as exercise regulate adiposity in adults, but the effects of exercise during pregnancy on infant adiposity remain understudied. This report analyzed the relationship between prenatal exercise frequency, intensity, time, type, and volume (FITT-V) and infant adiposity, to better guide prenatal exercise prescription. Female participants [body mass index = 29.0 kg/m, 30.5 yr of age, with gravida = 1 and parity = 0, peak oxygen consumption (V̇o) = 21.9 mL/kg/min, and pregnant for 39.6 wk] were randomized to supervised exercise (aerobic, resistance, combination) or attention control for ∼24 wk during pregnancy. FITT-V metrics were analyzed from session records. Infant mesenchymal stem cells (MSCs), a model of infant adiposity, were collected from umbilical cord at delivery, adipogenically differentiated, and stained for lipids. Infant body fat percentage was estimated from skinfolds measured at 1 mo of age. Higher weekly exercise volume correlated with lower infant body fat ( = 0.12, = 0.03) and MSC lipids ( = 0.13, = 0.01). Weekly exercise frequency ( = 0.06, = 0.10) and total volume ( = 0.19, = 0.002) influenced adiposity. Subscapular skinfolds were notably affected by exercise ( = 0.27, < 0.001). We conclude that in utero exposure to exercise beyond minimum recommendations is associated with reduced infant adiposity. Specifically, our findings suggest that exercising below 450 metabolic equivalent (MET)·min/wk, e.g., exercising at an average of 3 METs for 150 min/wk or 5 METs for 90 min/wk, excludes individuals from these offspring health benefits. This study was the first to test how specific prenatal exercise dose, i.e., the FITT-V (frequency, intensity, time, type, volume) metrics, could influence the storage of triglycerides in infant adipogenic mesenchymal stem cells (MSCs). Prenatal exercise led to a reduction in infant whole body fat percentage (BF%), which was reflected by lower lipid storage in infant MSCs. Changes in lipid content were observed in offspring born to participants exercising beyond the minimum recommended weekly volume, 450 metabolic equivalent (MET)·min/wk.
Noradrenergic input to hypoglossal motoneurons is mediated by interneurons located in prehypoglossal region.
Jackson SE, Frasson Dos Reis L, Xu K … +2 more , Rukhadze I, Fenik VB
J Appl Physiol (1985) · 2026 Apr · PMID 41661729 · Full text
The genioglossus (GG) muscle of the tongue, innervated by hypoglossal motoneurons, plays a critical role in the pathophysiology of obstructive sleep apnea. The state-dependent activity of the hypoglossal motoneurons is l...
The genioglossus (GG) muscle of the tongue, innervated by hypoglossal motoneurons, plays a critical role in the pathophysiology of obstructive sleep apnea. The state-dependent activity of the hypoglossal motoneurons is largely maintained by excitatory noradrenergic drive. However, this drive was hypothesized to be mediated by unidentified perihypoglossal neurons. We used microinjections of phenylephrine or prazosin, α1-adrenoceptor agonist and antagonist, respectively, into the medullary reticular formation rostral to the hypoglossal nucleus to locate these neurons. The phenylephrine or prazosin was microinjected into the hypoglossal nucleus and into rostral medullary regions while recording spontaneous activity in GG and diaphragm muscles in anesthetized C57bl/6J mice. The microinjections of phenylephrine/prazosin elicited, respectively, excitatory/inhibitory responses in the GG muscle, which had minimal latencies when injected into a limited region just rostral to the hypoglossal nucleus, which we termed the "prehypoglossal region" (PHR). In isoflurane-anesthetized mice, phenylephrine injected into the PHR induced large increases in GG muscle activity (21.8 ± 3.5 vs. baseline 4.50 ± 0.86, arbitrary units). These phenylephrine-induced responses from the PHR were substantially stronger compared with those evoked from the hypoglossal nucleus (5.46 ± 1.3 vs. baseline 4.12 ± 0.73). However, in ketamine/xylazine-anesthetized mice, phenylephrine's ability to activate the GG muscle from the PHR was substantially blunted, which suggests that the ketamine-induced systemic antagonism of glutamatergic NMDA receptors may interfere with the response. Our findings suggest that the PHR contains interneurons that mediate the state-dependent noradrenergic drive to hypoglossal motoneurons, and that glutamate may be used as a mediator by PHR circuitry. PHR interneurons that transmit noradrenergic drive to hypoglossal motoneurons are located just rostral to the hypoglossal nucleus. Under isoflurane anesthesia, phenylephrine-induced excitation of PHR interneurons induced a fivefold increase in the amplitude of spontaneous genioglossus (GG) muscle activity as compared with limited GG muscle responses from the hypoglossal nucleus. Ketamine/xylazine anesthesia blunted the phenylephrine-PHR-elicited GG muscle excitation, which suggests an involvement of NMDA receptors in the control of GG muscle by PHR circuitry.
Attenuated myogenic response and contractility in middle cerebral arteries after cardiac arrest: a randomized experimental rat study.
Hansen FB, Brodersen KD, Secher N … +4 more , Prat-Duran J, Mogensen S, Simonsen U, Granfeldt A
J Appl Physiol (1985) · 2026 Mar · PMID 41661671 · Publisher ↗
Neurological injury, the leading cause of death after cardiac arrest resuscitation, has been shown to worsen progressively in the postcardiac arrest period. This deterioration may be due to impaired cerebral autoregulati...
Neurological injury, the leading cause of death after cardiac arrest resuscitation, has been shown to worsen progressively in the postcardiac arrest period. This deterioration may be due to impaired cerebral autoregulation, leading to harmful alterations in cerebral perfusion. We aimed to investigate the myogenic response, a key component of cerebral autoregulation, in the postcardiac arrest period. Rats were anesthetized, intubated, catheterized, and randomized into a sham group or cardiac arrest group. Cardiac arrest rats underwent 7 min of cardiac arrest. Subsequently, groups were observed for 4 h. Middle cerebral arteries (MCAs) were examined using pressure myography and confocal microscopy. qPCR was performed on the posterior communicating arteries. The myogenic response to increasing levels of intraluminal pressure was significantly reduced in MCAs from cardiac arrest rats compared with sham ( = 0.02, mixed model for repeated measures). The MCAs demonstrated comparable contraction with increasing concentrations of U46619, but a high K solution yielded significantly lower vasoconstriction in cardiac arrest MCAs compared with sham (sham: 152 ± 5 µm and cardiac arrest: 166 ± 3 µm, = 0.03). qPCR showed reduced gene expression of cytoplasmic tyrosine kinase ABL1, rho-associated protein kinase 1, and endothelial nitric oxide synthase in cerebral arteries from cardiac arrest rats compared with sham. Confocal microscopy revealed no significant differences in nitrotyrosine or F-actin expression between groups in MCAs. In rat MCAs, the myogenic response, myogenic tone, and the maximum contraction are significantly reduced 4 h after cardiac arrest. Our results suggest impaired calcium-sensitizing mechanisms in cerebral myogenic vasoconstriction after cardiac arrest. Cerebral autoregulation is impaired in the postcardiac arrest period, potentially altering cerebral blood flow and exacerbating neurological injury after resuscitation. To our knowledge, the current study is the first to demonstrate that cerebral arteries exhibit reduced myogenic response, tone, and contractility in an animal model following resuscitation from cardiac arrest. These alterations in vasoreactivity appear to result, at least in part, from decreased calcium sensitivity in cerebral vascular smooth muscle cells.
Energy and fluid balance during a 214-km winter ultraendurance race: a case study.
Wehmanen KW, Ruby BC, Shriver TC … +5 more , Ravelli MN, Kipp S, McDaniel J, Petushek EJ, Elmer SJ
J Appl Physiol (1985) · 2026 Apr · PMID 41651468 · Publisher ↗
The upper limits for total energy expenditure (TEE) and water turnover (rHO) in humans have been reported during several continuous single-day ultraendurance races (running, cycling, and triathlon). Currently, the upper...
The upper limits for total energy expenditure (TEE) and water turnover (rHO) in humans have been reported during several continuous single-day ultraendurance races (running, cycling, and triathlon). Currently, the upper limits for TEE and rHO during continuous single-day activity in cold weather (<0 °C) remain unknown. The Arrowhead Ultra is one of the coldest ultraendurance races in North America and provides a unique opportunity to answer these questions. Racers select a bicycle, cross-country skis, or foot travel to traverse a 214-km snow-covered trail (altitude range: 345-426 m; 2,030-m elevation gain). Historically, approximately one-half of the racers complete the event. In this case study, we assessed TEE and rHO from the racer [cyclist: age: 22 yr; height: 1.84 m; body mass: 87.7 kg; and maximal oxygen consumption (V̇o): 5.0 LO·min] who won the 2025 Arrowhead Ultra (17.9 h; -13 to -1 °C) using the doubly labeled water method. Total energy and fluid intake were recorded to assess energy and fluid balance. Mean heart rate was 141 beats·min (71% of maximum heart rate). TEE was 63.9 MJ (15,273 kcal; 9.6 times basal metabolic rate) while total energy intake was 33.2 MJ (7,941 kcal). Mean carbohydrate intake was 88 g·h. Water turnover was 17.7 L, yielding a rHO/TEE ratio of 0.28 L·MJ for the race. The cyclist demonstrated high TEE and rHO that were comparable to values from other ultraendurance athletes competing in a range of temperatures (3-34°C). Notably, rHO from this cyclist was higher compared to athletes performing other ultratype endeavors in cold weather conditions (-25 to -19 °C). Our observations shed light on energy and fluid demands during continuous single-day activity in the cold and have endurance training and performance implications. In this short report, we detail new data on the upper limits of human energy expenditure (9.6 times basal metabolic rate) and water turnover (10.5 L·12 h) during continuous single-day exercise in the cold. Our results indicated elevated energy use, and impressively, water turnover comparable to exercise in warmer conditions. These findings have implications for training and endurance performance of strenuous exercise in cold weather environments.
Global versus regional effects of PEEP on recruitment and strain: insights from preclinical and clinical studies.
Menga LS, Sousa MLA, Sun N … +15 more , Roldan R, Brault C, Pellegrini M, Ko M, Damiani LF, Phoophiboon V, Dubo S, Vieira F, Rodrigues A, Docci M, Chen L, Schreiber A, Slutsky AS, Post M, Brochard L
J Appl Physiol (1985) · 2026 Mar · PMID 41643657 · Publisher ↗
In acute respiratory distress syndrome (ARDS), regional aeration is often gravity-dependent, with positive end-expiratory pressure (PEEP) recruiting the lung dorsally. Although recruitability can be assessed globally, ou...
In acute respiratory distress syndrome (ARDS), regional aeration is often gravity-dependent, with positive end-expiratory pressure (PEEP) recruiting the lung dorsally. Although recruitability can be assessed globally, our aim was to determine the impact of PEEP on regional recruitability and regional strain. To achieve a large representation of recruitability, we studied two preclinical porcine models of acute lung injury [(ALI) 19 symmetrical and 10 asymmetrical ALI], 20 patients with ARDS of mixed etiology (mixed ARDS), and 15 with COVID-19 ARDS. All study subjects underwent a single-breath derecruitment maneuver from high-to-low PEEP to quantify recruitability using the recruitment-to-inflation ratio (R/I). The regional effects of PEEP on strain were assessed using electrical impedance tomography (EIT). Symmetrical ALI animals had the highest R/I (1.39 [1.04-1.66]), followed by mixed ARDS (1.06 [0.70-1.23]), COVID-19 ARDS (0.66 [0.51-0.98]), and asymmetrical ALI (0.45 [0.22-0.85]). Dorsal regions had the highest recruitability ( = 0.001), and differences between dorsal and ventral regions were higher in recruitable subjects. Increasing PEEP decreased ventral dynamic strain ( < 0.01), with varying effects on dorsal dynamic strain. A paradoxical increase in dorsal dynamic strain associated with ventral hyperinflation could be observed across all groups, but more frequently in the less recruitable subjects. It was predicted by the EIT ventral-to-dorsal shift in ventilation normalized to the change in dorsal lung volume ( < 0.001). In animals and patients with varying recruitability, a higher global R/I is associated with a higher effect on the dorsal versus ventral R/I. PEEP can paradoxically increase dorsal strain due to ventral overdistention, and this is detectable by EIT. Dorsal regions are more recruitable than ventral, decreasing their dynamic strain with PEEP, but relative PEEP effects vary across ARDS phenotypes with different global recruitability. The higher the global recruitability, the higher the effect on the dorsal part. This was demonstrated across two acute lung injury (ALI) animal models and two patient cohorts, mixed ARDS, and COVID-19 ARDS. PEEP can paradoxically increase dynamic dorsal strain despite recruitability if ventral overdistention occurs. EIT can detect this.
Estrogen receptor alpha determines sex-specific cardiorespiratory and autonomic responses to intermittent hypoxia in mice.
Aka E, Marcouiller F, Joseph V
J Appl Physiol (1985) · 2026 Mar · PMID 41643644 · Publisher ↗
Despite the evidence that responses to intermittent hypoxia (IH) vary between sexes, potentially underlying sex-specific comorbidities of sleep apnea, the roles that sex hormones play during exposure to IH in rodent mode...
Despite the evidence that responses to intermittent hypoxia (IH) vary between sexes, potentially underlying sex-specific comorbidities of sleep apnea, the roles that sex hormones play during exposure to IH in rodent models remain poorly defined. The estradiol receptor α (ERα), expressed in structures of the peripheral and central nervous system, contributes to autonomic regulations and control of arterial blood pressure; accordingly, we tested the hypothesis that ERα modulates respiratory and heart rate variability in male and female mice exposed to IH. We used adult wild-type (WT) and ERα knockout (ERαKO) mice of both sexes for whole body plethysmography, arterial blood pressure, and ECG recordings before and after 14 days of IH (6% O, 12 cycles/h, 12 h/day). Compared with males, WT females exhibited greater respiratory variability and higher apnea frequency before IH exposure. In females, ERα deletion increased body weight and reduced postsigh apnea frequency before IH exposure. In ANCOVA/GLM models, body weight was a significant negative covariate for postsigh and spontaneous apneas before IH exposure, whereas sex and genotype effects were not significant after adjustment. IH exposure increased the mean and diastolic blood pressures only in WT males. IH also increased apneas frequency in WT females, an effect markedly reduced by ERα deletion. Similarly, heart rate variability increased in WT females following IH, reflecting enhanced parasympathetic modulation, an effect absent in ERαKO females and in WT or ERαKO males. We conclude that in female mice, deletion of ERα prevents IH-induced improvement of heart rate variability. We show that ) the intrinsic variability of the breathing pattern and the frequency of apneas both before and after exposure to intermittent hypoxia (IH) are higher in WT female mice compared with males, ) higher body weight is significantly associated with lower apnea frequency in ERαKO female mice, and ) in female mice, the expression of ERα appears to be essential to increase heart rate variability following exposure to IH.
The time course of exercise-induced expiratory and inspiratory muscle fatigue.
Hardy TA, Chadwick MR, Ferguson C … +2 more , Cross TJ, Taylor BJ
J Appl Physiol (1985) · 2026 Feb · PMID 41617217 · Publisher ↗
Inspiratory muscle fatigue develops during exercise before intolerance. The expiratory muscles are less resistant to fatigue compared to the inspiratory muscles, but the time course of inspiratory and expiratory muscle f...
Inspiratory muscle fatigue develops during exercise before intolerance. The expiratory muscles are less resistant to fatigue compared to the inspiratory muscles, but the time course of inspiratory and expiratory muscle fatigue during exercise has not been compared. Ten healthy adults (25 ± 5 yr; 2 females) cycled on three separate occasions at 25% of the difference between estimated critical power and peak ramp incremental power (severe intensity domain) for ) 100% of time to the limit of tolerance (T; 10.2 ± 2.6 min); ) 75% T (7.7 ± 1.9 min); and ) 50% T (5.1 ± 1.3 min). Expiratory and inspiratory muscle fatigue were quantified as the pre- to postexercise reduction in the gastric (Pga) and diaphragm (Pdi) twitch pressure response to magnetic stimulation of the thoracic and cervical nerves, respectively. Pga and Pdi were reduced from baseline values after 50% T (11.9 ± 8.2% and 9.5 ± 9.2%; both < 0.05). The magnitude of expiratory and inspiratory muscle fatigue increased progressively at 75% T (20.0 ± 12.6% and 15.2 ± 10.1%; both < 0.05) and 100% T (30.3 ± 15.6% and 22.4 ± 12.5%; both < 0.05), but there was no difference between muscle groups ( > 0.05). Expiratory and inspiratory muscle fatigue develops relatively early during severe intensity exercise and increases progressively in magnitude by exercise intolerance. The onset and progression of respiratory muscle fatigue during exercise are not different between the expiratory and inspiratory muscles. During severe exercise, expiratory and inspiratory muscle fatigue develops by ∼50% of the tolerable exercise duration. The magnitude of expiratory and inspiratory muscle fatigue increases progressively toward exercise intolerance but is not different between muscle groups; this is despite the expiratory muscles being less fatigue-resistant. Inspecting esophageal and gastric twitches via cervical stimulation, we speculate that the progressive magnitude of exercise-induced inspiratory muscle fatigue is a function of recruitment and fatigue of the accessory inspiratory muscles.
From respiratory limitation to dynamic depletion of mechanical-ventilatory reserves: a paradigm shift to probe exertional dyspnea with clinical exercise testing.
Hijleh AA, Berton DC, O'Donnell DE … +1 more , Neder JA
J Appl Physiol (1985) · 2026 Mar · PMID 41616805 · Publisher ↗
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 exert...
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 [Formula: see text], increased physiological dead space, or high CO 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 pretest likelihood of abnormality.
Does excess exercise-induced cardiac activation at exercise onset independently generate increases in cardiovascular circuit flow?
Zedic AK, Mladen SPS, Forbes SPA … +1 more , Tschakovsky ME
J Appl Physiol (1985) · 2026 Mar · PMID 41616803 · Publisher ↗
We tested the hypothesis that excess cardiac activation (ECA) generates increased cardiovascular circuit flow at the onset of exercise. Thirty participants (14 females) performed 30 s of right-legged knee extension/flexi...
We tested the hypothesis that excess cardiac activation (ECA) generates increased cardiovascular circuit flow at the onset of exercise. Thirty participants (14 females) performed 30 s of right-legged knee extension/flexion exercise at 50% of one-legged WR to assess the normal cardiovascular adjustment at the onset of single-leg exercise (control; CON). ECA in isolation was accomplished in separate trials by initiating exercise with both the right leg and the occluded left leg (each at 50% one-legged WR) to generate additional muscle mass activation of autonomic cardiac control without allowing the exercising left leg circulation to add to the cardiovascular circuit. Central (finger photoplethysmography) and peripheral (Doppler ultrasound) hemodynamics were measured continuously. ECA increased cardiac activation versus CON (Δ heart rate; 35.3 ± 8.4 vs. 24.5 ± 8.7 beats/min, < 0.0001), which elevated ΔQ̇ (4.62 ± 1.62 vs. 3.48 ± 1.51 L/min, < 0.001) as Δ stroke volume was not different between conditions. ECA increased Δ mean arterial pressure (11.9 ± 5.8 vs. 5.5 ± 5.6 mmHg, < 0.0001) via ΔQ̇, as Δ total vascular conductance was also greater during ECA (36.6 ± 18.3 vs. 31.3 ± 15.1 mL/min/mmHg, = 0.0120). Δ exercising leg blood flow (LBF; 2,594.3 ± 639.6 vs. 2,425.1 ± 550.9 mL/min, = 0.0179), but not Δ leg vascular conductance, was greater in ECA vs. CON. These findings demonstrate that excess exercise-induced cardiac activation can create a greater increase in Q̇ and exercising leg perfusion at exercise onset without a change in exercising leg vasodilation magnitude during sub-maximal knee flexion/extension exercise. Whether increasing cardiac activation above normal can increase cardiovascular circuit blood flow above normal at exercise onset in humans remained unclear. We found that excess exercise-induced cardiac activation created a greater increase in cardiac output via greater heart rate increases. Furthermore, exercising leg perfusion also increased to a greater extent due to elevated arterial blood pressure created by greater cardiac output. In conclusion, increased cardiac activation can improve cardiovascular circuit flow responses at exercise onset.
Kidney injury risk during prolonged endurance running: lessons from the field.
McKenna ZJ, Atkins WC, Babcock MC … +4 more , Grosicki GJ, Linder BA, McDermott BP, Robinson AT
J Appl Physiol (1985) · 2026 Mar · PMID 41615405 · Publisher ↗
Marathon and ultramarathon runners commonly exhibit postrace rises in biomarkers of acute kidney injury. Although these perturbations are generally transient and resolve without treatment, rare but serious cases of clini...
Marathon and ultramarathon runners commonly exhibit postrace rises in biomarkers of acute kidney injury. Although these perturbations are generally transient and resolve without treatment, rare but serious cases of clinically significant kidney injury in endurance athletes have been documented postrace. 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: ) the primary mechanisms by which endurance exercise contributes to acute kidney injury; ) factors that may modulate kidney injury risk in endurance athletes; ) recommendations and considerations for field-based studies; and ) 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. In addition, 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.
A novel method to estimate discharge-independent inhibition durations of spinal and brainstem circuits in humans.
Topkara Arslan B, Özyurt MG, Türker KS
J Appl Physiol (1985) · 2026 Mar · PMID 41615390 · Publisher ↗
Direct recordings from human motoneurons are not feasible; therefore, researchers have developed indirect methods to estimate postsynaptic potential profiles, that is, the functional inhibition or excitation, on firing m...
Direct recordings from human motoneurons are not feasible; therefore, researchers have developed indirect methods to estimate postsynaptic potential profiles, that is, 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 standardize 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 analyzed 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 standardized 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. Direct recordings from human motoneurons are not feasible; therefore, synaptic inhibition must be estimated indirectly. Experiments on rat brain slices allow accurate prediction of inhibition duration, independent of motor unit discharge rate. Applying these predictions in human studies has revealed discharge rate-independent functional inhibitions across various brainstem and spinal circuits. This approach offers robust estimates of functional inhibition, with potential clinical applications for monitoring neurological disorders that affect neural circuits.
Fluid-regulating hormones and plasma volume during 60 days of head-down bed rest with exercise during artificial gravity (BRACE).
Bryans CG, Mastrandrea CJ, Hedge ET … +5 more , Siebenmann C, Hargens AR, Karlsson LL, Hughson RL, Linnarsson D
J Appl Physiol (1985) · 2026 Mar · PMID 41615387 · Publisher ↗
Reductions in plasma volume (PV), a hallmark of spaceflight and its analog head-down-bed rest (HDBR), trigger compensatory release of renin and aldosterone to promote fluid retention. Artificial gravity (AG) and exercise...
Reductions in plasma volume (PV), a hallmark of spaceflight and its analog head-down-bed rest (HDBR), trigger compensatory release 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 fluid-regulating hormones and PV during HDBR compared with exercise or sedentary control groups. We hypothesized that exercise + AG would protect PV and maintain fluid-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 ( = 8), exercise ( = 8), or exercise + AG ( = 8) groups. Exercise group participants performed near daily 30 min supine moderate-to-high-intensity interval cycling throughout HDBR, whereas exercise + AG participants performed the same exercise during 30 min 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 ( < 0.001), blood volume ( < 0.001), and hemoglobin mass ( < 0.001) in all groups, and reductions were inversely correlated with an increase in active renin (all < 0.05; = -0.615, = -0.553, and = -0.426, respectively). Erythropoietin was reduced at HDBR day 3 ( < 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. Artificial gravity (AG) combined with exercise was proposed to protect plasma volume during head-down bed rest (HDBR). Our results suggest that by performing exercise with simultaneous AG, the previously identified beneficial effect of gravity-like exposure after exercise during prolonged HDBR is lost. The lack of benefit of simultaneous exercise and AG on plasma volume and fluid-regulating hormones is likely attributable to activation of the muscle pump, attenuating fluid shifts during AG countermeasure sessions.
Attenuated cyclooxygenase-mediated vasodilation in cutaneous microvasculature with no difference in platelet aggregation in women with endometriosis.
Williams AC, Martinez Yus M, Santhanam L … +1 more , Alexander LM
J Appl Physiol (1985) · 2026 Mar · PMID 41615377 · Full text
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 (Endo) with...
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 (Endo) 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 ( < 0.01). There were no differences between groups in platelet aggregation characteristics ( ≥ 0.10, all reagents, all characteristics). There were no differences between groups in COX metabolites (Thromboxane B, = 0.27; prostaglandin E2, = 0.70). Our findings suggest that COX-mediated vasodilation is attenuated in women with endometriosis and that platelet activity is not different between women with endometriosis and healthy women. We demonstrate attenuated cyclooxygenase-mediated vasodilation in women with endometriosis. In addition, we show no differences in platelet aggregation between women with and without endometriosis despite increased platelet count in the endometriosis group.
Independent directional tuning of the human triceps surae muscles during standing postural control.
Zaback M, Thompson CK
J Appl Physiol (1985) · 2026 Apr · PMID 41615326 · Full text
The triceps surae, composed of the soleus (SOL) and medial (MG) and lateral (LG) gastrocnemii, are synergists that act as a functional unit to plantarflex the ankle. However, anatomical differences suggest that each musc...
The triceps surae, composed of the soleus (SOL) and medial (MG) and lateral (LG) gastrocnemii, are synergists that act as a functional unit to plantarflex the ankle. However, anatomical differences suggest that each muscle is capable of generating distinct torques at the ankle, raising the possibility that each can be independently controlled to suit the needs of a given task. This possibility was explored by investigating the activation patterns of the triceps surae during two balance tasks that use different neuromechanical control strategies to maintain equilibrium. High-density surface EMG was recorded from the triceps surae of 14 healthy young adults during multiple trials of dual- and single-legged standing. Newly developed analyses examined how each muscle tuned its activity with center of pressure (COP) movement throughout 2-D space. During dual-legged standing, only the SOL and MG were active, and both tuned their activity uniformly with anteroposterior COP movement. By contrast, during single-legged standing, each muscle showed robust activation and significantly different directional tuning, with the LG most active before medial COP movement, whereas SOL and MG were most active before lateral COP movement. Further analyses demonstrated the LG could be activated entirely independent of the SOL and MG, and vice versa, with independent activation of each muscle causing different angular deflections of the COP during single-, but not dual-legged standing. These observations reveal a sophisticated level of neural control, whereby the nervous system exploits subtle differences between highly similar muscles to tune stabilizing torques in a task-dependent manner. By applying new analytical techniques to high-density surface EMG and kinetic data, we show that each triceps surae muscle produces directionally tuned torques that the nervous system exploits to regulate equilibrium in a task-dependent manner. No intramuscular differences were observed, suggesting that each triceps surae muscle is treated as homogeneous, but functionally distinct, actuators. This fractionated control of synergists may be critical to the maintenance of equilibrium and impaired by musculoskeletal and neurological disorders.
Low-energy cooling strategies modulate biomarkers of kidney injury risk in older adults exposed to very hot and dry heat.
McKenna ZJ, Schlader ZJ, Sarma S … +1 more , Crandall CG
J Appl Physiol (1985) · 2026 Feb · PMID 41609722 · Full text
Acute kidney injury (AKI) contributes to excess hospital admissions observed during heatwaves. We tested the hypothesis that water spray and fan use would modulate biomarkers of AKI risk in older adults exposed to 3 h of...
Acute kidney injury (AKI) contributes to excess hospital admissions observed during heatwaves. We tested the hypothesis that water spray and fan use would modulate biomarkers of AKI risk in older adults exposed to 3 h of very hot and dry heat. On each of 3 days (randomized), older adults (12 males/8 females; 66-84 yr) were exposed to 3 h of heating (47°C, 15% relative humidity) with no cooling intervention (control), water spray, or fan use. We assessed core temperature, fluid loss, biomarkers of AKI risk (AKIRISK score), and kidney function (plasma creatinine and cystatin C). The increase in core temperature was 1.3 ± 0.5°C (means ± SD) in control, 1.0 ± 0.2°C in water spray, and 1.9 ± 0.7°C in the fan trial. Fluid loss was 0.9 ± 0.2% in control, 0.4 ± 0.2% in water spray, and 1.5 ± 0.4% in fan. Compared with control, the AKIRISK score at end-heating was -0.18 [95% CI: -0.35, -0.02] lower in water spray ( = 0.047) and 0.26 [0.09, 0.44] higher in fan ( = 0.002). Repeated-measures correlations demonstrated positive associations between end-heating core temperature ( = 0.77; < 0.001) and fluid loss ( = 0.48; = 0.001), both relative to the end-heating AKIRISK score. Compared with control, end-heating plasma creatinine was not different ( = 0.43), but plasma cystatin C was 0.07 [-0.13, -0.01] mg/L lower ( = 0.025) in water spray. Compared with control, end-heating creatinine was 0.08 [0.03, 0.12] mg/dL higher ( < 0.001), and cystatin C was 0.07 [0.01, 0.13] mg/L higher ( = 0.026) in the fan trial. These findings suggest that in very hot and dry conditions, water spray can attenuate, whereas fans elevate heat-related increases in AKI risk biomarkers. Acute kidney injury contributes to the increased mobility and mortality reported during heatwaves. Air conditioning is protective but may not be available to all; thus, there is a need to identify non-air-conditioning-dependent cooling strategies. We show that water spray mitigates, but fans elevate heat-related increases in biomarkers of acute kidney injury in older adults exposed to 3 h of very hot and dry conditions.
Atrioventricular area difference assessed by exercise cardiovascular magnetic resonance shows impaired diastolic filling in patients with heart failure.
Edlund J, Östenson B, Åkesson J … +3 more , Heiberg E, Arheden H, Steding-Ehrenborg K
J Appl Physiol (1985) · 2026 Feb · PMID 41592758 · Publisher ↗
Heart failure (HF) is a complex clinical syndrome characterized by exercise intolerance. However, most diagnostic assessments are performed at rest, when many patients are asymptomatic. To better understand the underlyin...
Heart failure (HF) is a complex clinical syndrome characterized by exercise intolerance. However, most diagnostic assessments are performed at rest, when many patients are asymptomatic. To better understand the underlying pathophysiology, examination during exercise is needed. Hydraulic force, a newly identified mechanism of diastolic filling, is proportional to the difference in short-axis areas between the left ventricle and atrium, known as the atrioventricular area difference (AVAD). Although hydraulic force has been shown to augment diastolic filling during exercise in healthy individuals, its role in HF during exercise remains unexplored. This study aimed to investigate whether hydraulic forces impair or augment diastolic filling in patients with HF during exercise, using AVAD measurements from exercise cardiovascular magnetic resonance (CMR) imaging. We examined 13 healthy volunteers and 22 patients with HF at rest and during exercise using a CMR-compatible ergometer. AVAD was measured at end-systole (ES) and end-diastole (ED). In patients with HF, AVAD at ED decreased during exercise (from 17 ± 5 cm to 15 ± 6 cm, = 0.006), whereas it increased in healthy volunteers (from 16 ± 3 cm to 17 ± 3 cm, = 0.014). AVAD at ES decreased in both HF (from -2 ± 5 cm to -8 ± 5 cm, < 0.001) and healthy volunteers (from -3 ± 2 cm to -5 ± 3 cm, = 0.011). In conclusion, the results suggest impaired diastolic function during exercise in HF through reduced hydraulic force compared with rest. These findings provide new mechanistic insights and may partly explain the hallmark symptom of exercise intolerance in heart failure. Hydraulic force is a newly identified mechanism of diastolic function. This study is the first to assess hydraulic forces in patients with heart failure during exercise using cardiovascular magnetic resonance. In contrast to healthy individuals, hydraulic force decreased from rest to exercise in patients with heart failure, suggesting impaired diastolic filling. These findings offer new mechanistic insights into diastolic dysfunction during exercise and may help explain the hallmark symptom of exercise intolerance in heart failure.
Reply to Bossi and Matta.
Stalmans M, Tominec D, Lauriks W … +4 more , Robberechts R, Ramaekers M, Debevec T, Poffé C
J Appl Physiol (1985) · 2026 Feb · PMID 41575316 · Publisher ↗
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Correction for Bouchama et al., volume 138, 2025, p. 964-978.
J Appl Physiol (1985) · 2026 Feb · PMID 41575315 · Publisher ↗
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Targeting pulmonary arterial hypertension with aerobic training: anti-inflammatory and cardioprotective effects enhance survival in experimental models.
de Araújo Alves CC, Santos RS, Rocha NN … +5 more , Félix NS, Capelozzi VL, Goulart CDL, Rocco PRM, Silva PL
J Appl Physiol (1985) · 2026 Feb · PMID 41569635 · Publisher ↗
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, increased right ventricular (RV) afterload, and high mortality. We investigated whether moderate aerobic training (AT) modulates in...
Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, increased right ventricular (RV) afterload, and high mortality. We investigated whether moderate aerobic training (AT) modulates inflammation, cardiopulmonary function, and survival in a monocrotaline (MCT)-induced PAH model. Male Wistar rats were randomized to nontrained (NT) or AT groups and treated with saline (SAL) or MCT: NT-SAL, NT-PAH, AT-SAL, and AT-PAH. AT consisted of treadmill exercise at ∼60% maximal oxygen consumption (V̇o), 5 days/wk for 5 wk, starting 3 wk after PAH induction. Outcomes included cardiac function [echocardiography and pulmonary acceleration time (PAT)/pulmonary ejection time (PET)], lung mechanics, histology (Movat pentachrome, diffuse alveolar damage, and transmission electron microscopy), inflammatory biomarkers, and survival. Compared with NT-PAH, AT-PAH animals showed higher PAT/PET ( = 0.003), smaller RV area ( = 0.003), lower Fulton index ( = 0.002), and reduced hepatic congestion ( = 0.002). Lung elastance ( = 0.006), parenchymal collagen ( = 0.007), bronchoalveolar lavage fluid total cells ( = 0.04), and neutrophils ( < 0.001) were lower in AT-PAH. Pulmonary arterioles exhibited higher IL-10 and lower IL-4, TNF-α, and VEGF (all < 0.001). Histology and ultrastructural analyses revealed reduced vascular remodeling, lower diffuse alveolar damage scores, and preserved lung and myocardial architecture (all < 0.05). Survival was higher in AT-PAH (80% vs. 60%, = 0.04). In conclusion, moderate AT before and after PAH induction improves RV-pulmonary artery coupling, reduces fibrosis and inflammation, preserves organ ultrastructure, and enhances survival. Integrating survival endpoints with noninvasive hemodynamics and dual-organ ultrastructural assessment provides mechanistic insight, supporting aerobic exercise as a potential nonpharmacological strategy in PAH. Further preclinical and clinical studies are needed to define optimal protocols and translational potential. In just 5 wk, moderate aerobic training (AT) conferred a survival advantage in experimental pulmonary arterial hypertension (PAH), while simultaneously mitigating key pathological features, including right ventricular strain, pulmonary vascular remodeling, inflammation, and fibrosis. These coordinated, multisystem benefits were achieved through a practical, low-cost intervention, underscoring exercise capacity not only as a functional outcome but also as a potential prognostic indicator in PAH. Although highly promising, clinical translation remains premature and will require validation in additional preclinical models and well-designed clinical trials.
A theory for why jugular vein thromboses develop in space.
Buckey JC, Lan M, Phillips SD … +1 more , Archambault-Leger V
J Appl Physiol (1985) · 2026 Feb · PMID 41556830 · Publisher ↗
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