Leonie Blattmann, Daniel Hamacher, Ross Tucker, Laura Healey, Joel Mason
{"title":"Supershoes or superhumans? A controlled analysis of sex-specific road-running performance evolution in the era of advanced footwear technology.","authors":"Leonie Blattmann, Daniel Hamacher, Ross Tucker, Laura Healey, Joel Mason","doi":"10.1152/japplphysiol.90174.2026","DOIUrl":"10.1152/japplphysiol.90174.2026","url":null,"abstract":"<p><p>Advanced footwear technology (AFT) improves running economy and is credited with recent performance improvements in road running, with observational analyses consistently demonstrating that women have improved more than men. In contrast, laboratory studies generally report similar running economy responses to AFT in both sexes, leaving the observational-experimental divergence unresolved. A fundamental limitation of observational work is the absence of a control condition, making it impossible to separate AFT-related gains from concurrent performance trends. We addressed this by comparing performances between pre-AFT (2009-2015) and AFT (2017-2024) eras across road-running events (10 km, half marathon, marathon) and throwing events, the latter serving as an active control condition exposed to several shared broad temporal influences within elite athletics but unaffected by advances in footwear technology. The top 50 performances per event, era, and sex were converted to World Athletics points and analyzed using linear mixed-effects models. Performances improved between eras (β = 0.294, <i>P</i> < 0.001), with gains substantially larger in road running than in throwing (β = 0.731, <i>P</i> < 0.001). The sex-specific pattern of improvement also differed between event categories (era × event type × sex interaction, β = 0.786, <i>P</i> < 0.001): road-running improvements were greater in women than men (4.51% vs. 2.62%), whereas throwing improvements did not differ by sex (0.93% vs. 1.15%). This sex-specific divergence between event families strengthens ecological evidence that AFT contributed to greater gains in women's road-running performance than men's, although concurrent running-specific influences cannot be excluded. The contrast with laboratory findings raises the possibility that conventional protocols may not fully capture sex-specific competitive effects of AFT.<b>NEW & NOTEWORTHY</b> Elite women's road-running performance improved substantially more than men's during the era of advanced footwear technology (AFT). In contrast, throwing events, exposed to similar era-level trends but unaffected by footwear, showed no comparable sex difference. This comparison provides novel ecological evidence supporting the notion that AFT contributed to greater road-running performance gains in women than men and raises the possibility that current laboratory protocols may not fully capture sex-specific competitive effects of AFT.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1229-1239"},"PeriodicalIF":3.7,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ferenc Peták, Ádám L Balogh, Domonkos Schulcz, Éva Zöllei, József Tolnai, Gergely H Fodor, Barna Babik
{"title":"Intrabreath oscillometry reveals phase-dependent resistive abnormalities in respiratory mechanics after severe COVID-19.","authors":"Ferenc Peták, Ádám L Balogh, Domonkos Schulcz, Éva Zöllei, József Tolnai, Gergely H Fodor, Barna Babik","doi":"10.1152/japplphysiol.00287.2026","DOIUrl":"10.1152/japplphysiol.00287.2026","url":null,"abstract":"<p><p>Post-COVID syndrome is often associated with persistent respiratory symptoms despite largely unremarkable conventional pulmonary function tests, suggesting the presence of subtle alterations in respiratory mechanics. We hypothesized that phase-resolved analysis of respiratory impedance would reveal dynamic abnormalities not captured by standard endpoint-based measures. In this prospective observational study, survivors of severe COVID-19 requiring veno-venous extracorporeal membrane oxygenation (<i>n</i> = 9) were evaluated 2 yr after recovery and compared with matched healthy controls (<i>n</i> = 9). Respiratory system impedance was assessed using intrabreath oscillometry at 5 Hz. Phase-dependent mechanical behavior was characterized by inspiratory-expiratory differences in phase-averaged resistance and reactance (Δ<i>R</i><sub>av</sub>, Δ<i>X</i><sub>av</sub>), end-tidal differences (Δ<i>R</i><sub>end</sub>, Δ<i>X</i><sub>end</sub>), and resistance and reactance loop areas (<i>R</i><sub>loop</sub>, <i>X</i><sub>loop</sub>). Post-COVID patients exhibited significantly elevated end-expiratory resistance (<i>P</i> = 0.02), whereas end-inspiratory resistance did not differ significantly between groups. Δ<i>R</i><sub>av</sub> (<i>P</i> = 0.01) and <i>R</i><sub>loop</sub> (<i>P</i> = 0.03) were reduced compared with controls, whereas Δ<i>R</i><sub>end</sub>, Δ<i>X</i><sub>av</sub>, Δ<i>X</i><sub>end</sub>, and <i>X</i><sub>loop</sub> did not differ significantly. These findings indicate altered phase-dependent mechanics in post-COVID patients, characterized by elevated end-expiratory resistance and attenuated within-breath resistance modulation. Intrabreath analysis of respiratory impedance thus provides complementary information on time-varying respiratory mechanics beyond conventional whole breath oscillometry and may enable more sensitive characterization of subtle mechanical dysfunction.<b>NEW & NOTEWORTHY</b> Survivors of severe COVID-19 requiring V-V ECMO exhibit phase-specific abnormalities in respiratory mechanics beyond those detected by conventional whole breath measures. Intrabreath oscillometry revealed elevated end-expiratory resistance and attenuated within-breath resistance modulation, indicating altered phase-dependent resistive mechanics. These findings highlight the complementary value of phase-resolved impedance analysis for characterizing subtle post-COVID respiratory mechanical dysfunction.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1219-1227"},"PeriodicalIF":3.7,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ricardo Mora-Rodriguez, Diego Mora-Gonzalez, Alfonso Moreno-Cabañas, Felix Morales-Palomo, Lucia Gonzalez-García, Lucas Martin-Gomez, Celia Ortega-Alcalde, Marina Mora-Gonzalez, Jesus G Pallares
{"title":"Elevations in blood lactate by exogenous infusion blunts exercise-stimulated whole body lipolysis in healthy individuals: a randomized controlled trial.","authors":"Ricardo Mora-Rodriguez, Diego Mora-Gonzalez, Alfonso Moreno-Cabañas, Felix Morales-Palomo, Lucia Gonzalez-García, Lucas Martin-Gomez, Celia Ortega-Alcalde, Marina Mora-Gonzalez, Jesus G Pallares","doi":"10.1152/japplphysiol.00361.2026","DOIUrl":"10.1152/japplphysiol.00361.2026","url":null,"abstract":"<p><p>The purpose of this study is to determine in humans whether lactate inhibits exercise-stimulated lipolysis, fat oxidation, and plasma glucose turnover. Eight healthy active individuals (3 women) completed four trials in a semirandomized order. In two trials, subjects exercised for 60 min at 65 ± 11% (mean ± SD) of maximal aerobic power ([Formula: see text]) while receiving isovolumetric infusions of either sodium lactate [moderate intensity (MOD) + LACT trial] or saline (MOD trial). In another trial, exercise intensity was increased to 82 ± 11% of [Formula: see text] [intense exercise (INT) trial] to match lactate concentrations to those in the MOD + LACT trial. A trial without exercise was included. Stable isotopes of glycerol and glucose were infused to assess whole body lipolysis (Ra glycerol) and glucose turnover rates (Ra glucose). Fat and carbohydrate oxidation were measured using indirect calorimetry. Basal metabolic rate and plasma concentrations of lactate, glucose, insulin, free fatty acids, and glycerol were similar across trials. Plasma lactate was clamped at 4.31 ± 1.68 mM during the MOD + LACT trial, which tripled MOD concentrations (1.42 ± 0.93 mM; <i>P</i> = 0.001) and matched INT concentrations (4.39 ± 1.25 mM; <i>P</i> = 0.819). MOD + LACT blunted the exercise-induced elevation in Ra glycerol of MOD (average during exercise, 7.9 ± 2.0 vs. 10.5 ± 2.2 µmol·kg<sup>-1</sup>·min<sup>-1</sup>; <i>P</i> = 0.014). However, fat oxidation rates were similar in MOD + LACT and MOD (7.70 ± 2.02 vs. 7.38 ± 1.47 µmol·kg<sup>-1</sup>·min<sup>-1</sup>; <i>P</i> = 0.612) but reduced during INT (5.30 ± 2.93 µmol·kg<sup>-1</sup>·min<sup>-1</sup>; <i>P</i> = 0.045). Ra glucose, plasma glucose, and insulin were elevated during INT but not affected by lactate infusion. Raising circulating lactate concentrations to levels observed during high-intensity exercise blunts exercise-stimulated whole body lipolysis. However, in these metabolically healthy individuals, that reduction was not sufficient to compromise fat oxidation during moderate-intensity exercise.<b>NEW & NOTEWORTHY</b> We examined the effect of high blood lactate levels on exercise-induced lipolysis. Lactate may contribute to the reduction in fat oxidation observed with increasing exercise intensity. It could also be responsible for the reduced exercise lipolysis observed in individuals with metabolic diseases. We found that raising blood lactate during exercise reduces exercise lipolysis by 25%. Thus, lactate blunts exercise-induced stimulation of lipolysis in humans, likely contributing to impaired fat metabolism in metabolically diseased individuals.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1045-1056"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Grant H Simmons, Logan J Heenan, Shannon Hugard, Benjamin J Smith, Kathryn M Lucernoni, Ollie Jay, Samuel N Cheuvront, Katelyn S Harker
{"title":"Partitioning secreted sweat in the measure of sweating efficiency during exercise.","authors":"Grant H Simmons, Logan J Heenan, Shannon Hugard, Benjamin J Smith, Kathryn M Lucernoni, Ollie Jay, Samuel N Cheuvront, Katelyn S Harker","doi":"10.1152/japplphysiol.90044.2026","DOIUrl":"10.1152/japplphysiol.90044.2026","url":null,"abstract":"<p><p>Sweating efficiency (SE), defined as the proportion of total secreted sweat that evaporates from the body, is a critical determinant of evaporative heat loss and fluid requirements during exercise. Despite its physiological importance, direct assessments of evaporated sweat loss (ESL) and SE during upright, clothed exercise are rare, owing to substantial methodological and logistical challenges. Here, we describe a modernized direct system for quantifying ESL, total sweat loss (TSL), and SE during exercise while simultaneously partitioning the end-exercise fate of all secreted sweat. The method combines precision measurement of mass change in a subject-ergometer-oil pan system to quantify ESL with gold-standard nude body mass measurements to determine TSL, after correction for nonsweat losses. Unevaporated sweat is further partitioned into dripped sweat, sweat retained in clothing, and sweat remaining on the skin. Equipment specifications, experimental workflow, validation procedures, and calculations are detailed to ensure that ESL and TSL correspond to the same exercise interval. This approach enables rigorous investigation of environmental, physiological, and apparel-related modifiers of sweating efficiency relevant to studies of human heat and fluid balance.<b>NEW & NOTEWORTHY</b> We present a direct, mass-balance methodology for determining evaporated sweat loss and sweating efficiency during upright, clothed exercise. The approach resolves key technical barriers limiting direct assessment of sweating efficiency and enables a complete accounting of secreted sweat by partitioning it into evaporated sweat, dripped sweat, sweat retained in clothing, and sweat remaining on the skin. This framework supports mechanistic evaluation of factors that promote and limit sweating efficiency and sweat evaporation during exercise-heat stress.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1073-1084"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keisho Katayama, Zachary R Oldham, Ziba Taherzadeh, Taha A Alhalimi, Patricia T Champagne, Tianyu Wang, Benjamin E Young, Shigehiko Ogoh, Paul J Fadel
{"title":"Diminished sympathoinhibition during the onset of low-intensity leg cycling in young Black males.","authors":"Keisho Katayama, Zachary R Oldham, Ziba Taherzadeh, Taha A Alhalimi, Patricia T Champagne, Tianyu Wang, Benjamin E Young, Shigehiko Ogoh, Paul J Fadel","doi":"10.1152/japplphysiol.00368.2026","DOIUrl":"10.1152/japplphysiol.00368.2026","url":null,"abstract":"<p><p>Previous studies have reported that non-Hispanic Black (BL) males exhibit augmented blood pressure (BP) responses to dynamic exercise relative to White males; however, the underlying mechanism(s) remain unclear. To our knowledge, no studies have examined the muscle sympathetic nerve activity (MSNA) response to dynamic exercise in BL adults. The purpose of this study was to examine potential racial differences in the sympathoinhibition that occurs at the onset of dynamic exercise. We hypothesized that cardiopulmonary baroreflex-mediated inhibition of sympathetic vasomotor outflow during the onset of low-intensity dynamic exercise is diminished in BL individuals. MSNA was recorded via microneurography of the left radial nerve in 9 BL (20 ± 3 yr, mean ± SD) and 11 non-Hispanic White (WH; 22 ± 4 yr) males. BP was measured by finger photoplethysmography, which was verified by automated brachial BP measures. Participants performed 3 min of bilateral leg cycling at 15 W on a cycle ergometer in the 70° semirecumbent position. MSNA burst frequency (BF) decreased during cycling in both groups; however, the decrease was significantly smaller (<i>P</i> < 0.001) in the BL group (-4.7 ± 3.7 bursts/min) than in the WH group (-11.3 ± 5.0 bursts/min). Mean BP increased during cycling in both groups, with no significant difference between the two groups (BL +7.4 ± 4.2 vs. WH +6.9 ± 7.1 mmHg, <i>P</i> = 0.958). These findings suggest that cardiopulmonary baroreflex-mediated inhibition of sympathetic vasomotor outflow at the onset of dynamic exercise is diminished in BL males compared to WH males.<b>NEW & NOTEWORTHY</b> It is unknown whether racial differences exist in sympathetic inhibition during the onset of dynamic exercise. We observed that the reduction in muscle sympathetic nerve activity during low-intensity leg cycling was less in young non-Hispanic Black males than in age-matched non-Hispanic White males. These findings suggest that cardiopulmonary baroreflex-mediated inhibition of sympathetic vasomotor outflow during leg cycling may be diminished in Black individuals.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1122-1128"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bianca Bittencourt Lucchetti, Juliana Arruda de Souza Monnerat, Gabriel Fernandes Teixeira, Juliana Mentzinger, Luiza Rocha, Helena Naly Miguens Rocha, Gabriel Ferreira Lima, Nadia Alice Vieira Motta, Fernanda Carla Ferreira Brito, Priscila Gomes Pereira, Jemima Fuentes Ribeiro da Silva, Natalia Galito Rocha, Antonio Claudio Lucas da Nóbrega, Renata Frauches Medeiros
{"title":"Aerobic training prevents the stress-induced endothelial dysfunction in male and female Wistar rats by different pathways.","authors":"Bianca Bittencourt Lucchetti, Juliana Arruda de Souza Monnerat, Gabriel Fernandes Teixeira, Juliana Mentzinger, Luiza Rocha, Helena Naly Miguens Rocha, Gabriel Ferreira Lima, Nadia Alice Vieira Motta, Fernanda Carla Ferreira Brito, Priscila Gomes Pereira, Jemima Fuentes Ribeiro da Silva, Natalia Galito Rocha, Antonio Claudio Lucas da Nóbrega, Renata Frauches Medeiros","doi":"10.1152/japplphysiol.01061.2025","DOIUrl":"10.1152/japplphysiol.01061.2025","url":null,"abstract":"<p><p>Variable stress contributes to cardiovascular morbidity by impairing endothelial function through oxidative stress, inflammation, and hormonal imbalance. These effects depend on sex-specific physiological responses. Although aerobic exercise is recognized for its vascular benefits, the mechanisms underlying these adaptations may differ between sexes. This study investigated the sex-specific effects of aerobic training on vascular function in Wistar rats subjected to variable stress. For this, male and female Wistar rats (<i>n</i> = 8/group) were assigned to control or stress groups (8 days using four different types of stressor stimuli), with or without aerobic training (treadmill, moderate intensity, 30 min/day for 8 wk). Thoracic aortic endothelial function was evaluated by acetylcholine-induced relaxation and phenylephrine-induced contraction. Antioxidant enzyme activity, nitrite concentration, and protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS at serine 1177 (p-eNOS<sup>ser1177</sup>), catalase, and superoxide dismutase (SOD) were measured. Stress impaired endothelium-dependent relaxation and increased vascular collagen content in both sexes. In females, stress reduced eNOS phosphorylation and nitrite bioavailability, while increasing antioxidant enzyme activity. In males, no significant changes in the eNOS-nitric oxide (NO) pathway were observed, but SOD activity increased. Aerobic training attenuated stress-induced vascular injury, predominantly through the upregulation of the eNOS-NO signaling pathway in females, whereas in males, possibly through another pathway related to oxidative status. These findings demonstrate the protective effects of aerobic exercise on vascular health in rats subjected to variable stress and underscore the existence of sex-specific mechanisms, with distinct molecular pathways mediating vascular adaptations in males and females. Furthermore, histological analysis revealed that aerobic training reversed collagen deposition and enhanced elastic fiber content.<b>NEW & NOTEWORTHY</b> Variable stress impairs vascular function in male and female rats, reducing endothelium-dependent relaxation and increasing collagen deposition. Aerobic training prevented these stress-induced vascular alterations, acting through nitric oxide upregulation in females and enhanced antioxidant defenses in males. These findings reveal sex-specific mechanisms underlying vascular protection by exercise and highlight aerobic training as an effective strategy to prevent stress-induced endothelial dysfunction and preserve vascular health.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1135-1146"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149060950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katelyn S Harker, Logan J Heenan, Shannon Hugard, Ollie Jay, Samuel N Cheuvront, Grant H Simmons
{"title":"Increasing humidity progressively reduces sweating efficiency similarly in males and females during exercise-heat stress.","authors":"Katelyn S Harker, Logan J Heenan, Shannon Hugard, Ollie Jay, Samuel N Cheuvront, Grant H Simmons","doi":"10.1152/japplphysiol.90043.2026","DOIUrl":"10.1152/japplphysiol.90043.2026","url":null,"abstract":"<p><p>This study compared the impact of increasing relative humidity (RH) on sweating efficiency (SE) in males and females exercising in the heat. Twenty recreationally active adults (10 females) completed four experimental trials (15, 35, 55, or 75% RH) in an environmental chamber (35°C) dressed in a T-shirt and shorts (and sports bra for females). Each study visit involved cycling for 60 min at a moderate intensity (H<sub>prod</sub> = 220 W·m<sup>-2</sup>) over a pan of mineral oil, situated above a high precision scale. Evaporated sweat loss (ESL; g) was measured as the change in mass of the combined subject + ergometer + oil pan system during exercise; total sweat loss (TSL; g) was measured as the change in nude mass from beginning to end-exercise. SE (%) was calculated as ESL/TSL × 100. The effects of RH and sex were assessed by two-way ANOVA; there was no significant RH × sex interaction for any variable. ESL was not different among 15, 35, and 55% RH, but was lower in 75% RH (<i>P</i> < 0.001). In contrast, TSL increased in each RH condition (all <i>P</i> < 0.001). Consequently, in both sexes SE progressively decreased (all <i>P</i> < 0.001) with increasing RH (males: 91.0 ± 3.1, 86.1 ± 4.8, 71.0 ± 9.3, and 46.4 ± 11.8%; females: 86.6 ± 3.7, 79.9 ± 5.7, 67.6 ± 6.7, and 44.3 ± 5.8%). These findings demonstrate that SE during exercise is progressively reduced by increasing RH and this effect is similar in males and females.<b>NEW & NOTEWORTHY</b> This study provides the first direct measurements linking the efficiency of sweating to the total fluid lost to evaporative cooling in upright, clothed, exercising subjects. These findings demonstrate that sweating efficiency during exercise is progressively reduced by increasing relative humidity, and this effect is similar in males and females. Decrements in sweating efficiency were related to sweat retained in the clothing.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1011-1021"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Masaki Kajimoto, Charles D Lawrence, Kyle S Bilodeau, Robert M DiBlasi, Brian Perfette, Kevin A Charette, Michael A Portman
{"title":"Neuronal and inducible nitric oxide synthase inhibitor for cerebral protection during deep hypothermic circulatory arrest in porcine hippocampus.","authors":"Masaki Kajimoto, Charles D Lawrence, Kyle S Bilodeau, Robert M DiBlasi, Brian Perfette, Kevin A Charette, Michael A Portman","doi":"10.1152/japplphysiol.01155.2025","DOIUrl":"10.1152/japplphysiol.01155.2025","url":null,"abstract":"<p><p>Neurological and neuropsychological deficits remain common following cardiovascular surgery in infants, yet the mechanisms underlying neuronal injury during deep hypothermic circulatory arrest (DHCA) are not fully understood. Our previous study demonstrated that inhaled nitric oxide (NO) attenuates DHCA-induced microglial activation and neurodegeneration. In this study, we investigated whether targeted inhibition of nitric oxide synthase (NOS) could reduce brain damage following DHCA. Based on previously published data, we used 2-iminobiotin, a selective inhibitor of both neuronal NOS (nNOS) and inducible NOS (iNOS). Juvenile piglets (∼7 wk old) underwent DHCA (cooled to 18°C) for 30 min, followed by rewarming either with or without a NOS inhibitor. Neuroinflammation and neuronal injury were assessed histologically in the hippocampus. TUNEL staining revealed that the NOS inhibitor (TUNEL-positive cells; median 1.3%) significantly alleviated neuronal damage compared with the nontreatment group (median 6.7%). NOS inhibitor also reduced the microglia activities related to the cerebral neuroinflammatory reaction after DHCA. NOS inhibition reduces neuronal degeneration and microglial activation in the hippocampus following DHCA. These findings suggest that the NOS inhibitor reduces neuronal degeneration by ameliorating inflammation.<b>NEW & NOTEWORTHY</b> DHCA demonstrates strongly activated microglia and neuronal damage in the hippocampus. A selective inhibitor of both nNOS and iNOS can reduce neuronal damage by ameliorating neuroinflammation.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1022-1031"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Danny Greig, Ruchi Rastogi, Chandra S J Miryala, B J Morgan, Lili Zhao, M Safwan Badr, Susmita Chowdhuri
{"title":"Acetazolamide mitigates opioid-associated sleep-disordered breathing.","authors":"Danny Greig, Ruchi Rastogi, Chandra S J Miryala, B J Morgan, Lili Zhao, M Safwan Badr, Susmita Chowdhuri","doi":"10.1152/japplphysiol.00444.2026","DOIUrl":"10.1152/japplphysiol.00444.2026","url":null,"abstract":"<p><p>Chronic prescription opioid use can exert ventilatory depression and increase loop gain to induce sleep-disordered breathing (SDB). Alternative therapies to mitigate opioid-associated SDB are needed. We sought to examine whether oral acetazolamide (ACZ) would reduce SDB in opioid-associated SDB by reductions in plant and/or by increasing cerebrovascular responsiveness to CO<sub>2</sub> (CCR). Nine adults with opioid-associated SDB were randomized to receive oral ACZ or placebo, in crossover fashion, for 6 days, with multiple measurements of awake CCR to hypercapnia on <i>day 4</i>, followed by measurements of apneic threshold, plant and controller gains (components of loop gain), using noninvasive mechanical ventilation during NREM sleep, and subsequent overnight polysomnography while still on the drug. Serum opioid and serum total CO<sub>2</sub> levels confirmed the use of opioid drug and ACZ, respectively. Compared with placebo, ACZ significantly reduced SDB severity (apnea-hypopnea index, 25.2 ± 8.3/h vs. 32.2 ± 8.2/h, <i>P</i> = 0.03; central apnea-hypopnea index 0.9 ± 0.3/h vs. 5.0 ± 1.1/h, <i>P</i> = 0.006, i.e., reduced 22% and 82%, respectively, with increased oxygen saturations). The reduction in SDB severity was accompanied with a significant reduction in plant gain with ACZ vs. placebo (4.0 ± 0.7 mmHg vs.6.6 ± 0.6 mmHg/L/min, <i>P</i> < 0.001), driven by ACZ-induced metabolic acidosis leading to increased eupneic minute ventilation (10.0 ± 1.4 vs. 6.8 ± 0.5 L/min, <i>P</i> = 0.04) and reduced eupneic end-tidal CO<sub>2</sub> (33.1 ± 1.2 mmHg vs. 41.6 ± 1.1 mmHg, <i>P</i> < 0.001). In contrast, the controller gain and CCR were unchanged with ACZ vs. placebo. Acetazolamide significantly mitigates opioid-associated sleep-disordered breathing via reduction in plant gain but without alterations in ventilatory chemoresponsiveness or cerebrovascular responsiveness.<b>NEW & NOTEWORTHY</b> This study demonstrates that oral acetazolamide significantly reduces opioid-associated sleep-disordered breathing (SDB) by reducing the plant gain, but without concurrently altering chemoresponsiveness or cerebrovascular responsiveness to carbon dioxide. This study is the first attempt to develop personalized therapies to mitigate breathing instability and SDB related to the ubiquitous use of opioid drugs.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1085-1097"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Association between motor unit remodeling and interindividual variability in muscle strength of older adults.","authors":"Masahiro Kuniki, Kaito Igawa, Yu-Ichi Noto, Ryosuke Takeda, Kohei Watanabe","doi":"10.1152/japplphysiol.90002.2026","DOIUrl":"10.1152/japplphysiol.90002.2026","url":null,"abstract":"<p><p>Marked interindividual variability in muscle strength exists among older adults, which cannot be fully explained by differences in muscle mass alone. Although motor unit remodeling is a characteristic feature of neuromuscular aging, whether variability in motor unit remodeling contributes to interindividual differences in muscle strength remains unclear. The purpose of this study was to examine the association between motor unit remodeling and muscle strength in older adults. Forty-nine older adults (25 men and 24 women) participated in this study. Motor unit parameters of the abductor pollicis brevis muscles were estimated using the MScanFit2 program. From the stimulus-response curve, motor unit number estimation (MUNE), size of motor units at the 50% mark of the cumulative amplitude expressed as a percentage (A50), the largest surface motor unit potential (L-sMUP) (motor unit size), estimated number of larger units making up 50% of the amplitude of compound muscle action potential (N50), and N50/MUNE (motor unit size composition) were derived. Associations between motor unit parameters and pinch strength were examined using partial correlation analyses adjusted for age, sex, and body weight. Sex-specific analyses were also performed. Pinch strength was significantly correlated with MUNE (<i>r</i> = 0.360; <i>P</i> = 0.014), A50 (<i>r</i><sub>s</sub> = -0.394; <i>P</i> = 0.007), L-sMUP (<i>r</i><sub>s</sub> = -0.389; <i>P</i> = 0.007), N50 (<i>r</i> = 0.416; <i>P</i> = 0.004), and N50/MUNE (<i>r</i> = 0.439; <i>P</i> = 0.002). These correlations remained significant only in men in sex-specific analyses. A lower motor unit number and shift toward larger motor unit sizes, reflecting greater motor unit remodeling, were associated with lower pinch strength. These findings suggest that motor unit remodeling may contribute to interindividual variability in muscle strength among older adults, particularly men.<b>NEW & NOTEWORTHY</b> This study demonstrated that, after adjustment for age, interindividual variation in motor unit remodeling is associated with muscle strength in older adults. Furthermore, by evaluating motor unit size composition in addition to conventional measures of motor unit number and size, this study provides a more comprehensive characterization of motor unit remodeling. These findings provide new insight into the neuromuscular mechanisms underlying marked interindividual variability in muscle strength during aging.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1099-1105"},"PeriodicalIF":3.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}