André L Teixeira, Jordan B Lee, Massimo Nardone, Jamie F Burr, Philip J Millar
{"title":"Interindividual variability in renal and muscle sympathetic responses to mental stress: contributions to blood pressure regulation.","authors":"André L Teixeira, Jordan B Lee, Massimo Nardone, Jamie F Burr, Philip J Millar","doi":"10.1152/japplphysiol.00575.2024","DOIUrl":"https://doi.org/10.1152/japplphysiol.00575.2024","url":null,"abstract":"<p><p>Laboratory-based mental stress induces consistent increases in arterial blood pressure, while sympathetic nerve activity (MSNA) responses are highly variable. Given the ability of sympathetic nervous system to be regulated in an organ-dependent manner, we hypothesized that inter-individual variability in renal sympathetic vasoconstriction interacts with MSNA to control blood pressure during mental stress. Herein, renal artery blood velocity (Doppler ultrasound; <i>n</i>=33, 19M/14F), MSNA (microneurography; <i>n</i>=25, 17M/8F), and beat-to-beat mean arterial pressure (MAP; finger photoplethysmography) were measured at rest and during mental stress (arithmetic task) in young, healthy adults. Renal vascular resistance (RVR) was calculated as an index of sympathetically mediated renal vasoconstriction. Participants were classified as negative, non-responders, or positive responders if RVR or MSNA was below, within, or above the baseline variability, respectively. The proportions of negative (24% vs. 36%), non-responders (18% vs. 16%), and positive (58% vs. 48%) responders were significantly different between RVR and MSNA-responder types, respectively (<i>P</i>=0.02). Within the participants in whom both MSNA and RVR were obtained (<i>n</i>=25), only 13 (52%) displayed concordant response patterns (3 negative, 1 non-responder, and 9 positive-responders). Participants were further classified based on the combination of RVR and MSNA responsiveness as typically negative, mixed, or typically positive responders. Within this sub-analysis, MAP reactivity was lower in typically negative compared to mixed and typically positive responders (2±3 mmHg vs. 6±3 mmHg vs. 7±3 mmHg, respectively; <i>P</i>=0.02). These findings suggest that the interindividual variability in renal and muscle vasoconstrictor responses contribute to blood pressure regulation during mental stress in young, healthy adults.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199226","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}
Francesco Paolo Lo Muzio, Birgit Zirngast, Barbara Karner, Martin Manninger, Mattia Fontana, Paul Steendijk, Heinrich Mächler, Giacomo Rozzi, Alessio Alogna
{"title":"Intraoperative Evaluation of Right Ventricular Mechanics in a Pressure-Overload Swine Model.","authors":"Francesco Paolo Lo Muzio, Birgit Zirngast, Barbara Karner, Martin Manninger, Mattia Fontana, Paul Steendijk, Heinrich Mächler, Giacomo Rozzi, Alessio Alogna","doi":"10.1152/japplphysiol.00143.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00143.2025","url":null,"abstract":"<p><strong>Objectives: </strong>Assessment of right ventricular (RV) mechanical performance during open chest surgery is typically based on invasive methods and subjective evaluations. This study developed a porcine model of acute progressive RV pressure overload to evaluate hemodynamic changes and validate the 3D-video kinematic assessment of the Videocardiograph (VCG).</p><p><strong>Methods: </strong>Seven healthy Landrace pigs were instrumented under fluoroscopic guidance with Swan-Ganz and RV conductance catheters. Following a median sternotomy, pulmonary artery banding (PB) was performed in two stages to induce minimal (PB<sub>min</sub>) and maximal (PB<sub>max</sub>) pressure overload. In a proof-of-concept experiment, different PB steps were performed to record both videos for the VCG and invasive pressure-volume assessments (PV-loop). Additionally, these videos were subjectively evaluated by five consultant surgeons, similar to clinical routine.</p><p><strong>Results: </strong>PB<sub>max</sub> significantly increased end-systolic pressure from baseline (21.17±3.31mmHg <i>vs</i> 39.85±7.82mmHg, p=0.001) and led to RV dilation, reduced ejection fraction (52.80±10.36% <i>vs</i> 33.99±9.88%, p=0.012), and decreased myocardial efficiency. In the proof-of-concept experiment, visual evaluations were highly variable among the cardiac surgeons, resulting in only a moderate reliability of their assessments (ICC=0.59 for RV-function; ICC=0.60 for filling status). VCG-derived epicardial <i>z</i>-axis displacements, systolic timing, diastolic velocity and volume demonstrated excellent relationships with PV-loop data.</p><p><strong>Conclusions: </strong>This study established a porcine model of progressive RV pressure overload with robust PV-loop assessment. VCG-derived epicardial kinematics reliably quantified RV mechanical activity and correlated with gold-standard hemodynamic measurements. This non-invasive, cost-effective method shows promise for early detection of acute RV dysfunction in the operating room and warrants further clinical investigation.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208583","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}
Rebekah J Osborne, Brett S Kirby, Matthew I Black, Anni Vanhatalo, Andrew M Jones
{"title":"Seven (.65) seconds away: the possibility and physiology of a women's sub-4 min mile.","authors":"Rebekah J Osborne, Brett S Kirby, Matthew I Black, Anni Vanhatalo, Andrew M Jones","doi":"10.1152/japplphysiol.00074.2025","DOIUrl":"10.1152/japplphysiol.00074.2025","url":null,"abstract":"","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1335-1340"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063948","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}
Fabio Sarto, Miloš Kalc, Evgeniia S Motanova, Martino V Franchi, Daniel Stashuk, Nina Murks, Giacomo Valli, Samuele Negro, Tomaž Prašnikar, Mladen Gasparini, Giovanni Martino, Giuseppe De Vito, Aleš Holobar, Boštjan Simunič, Rado Pišot, Marco V Narici
{"title":"Twenty-one days of bed rest alter motor unit properties and neuromuscular junction transmission in young adults.","authors":"Fabio Sarto, Miloš Kalc, Evgeniia S Motanova, Martino V Franchi, Daniel Stashuk, Nina Murks, Giacomo Valli, Samuele Negro, Tomaž Prašnikar, Mladen Gasparini, Giovanni Martino, Giuseppe De Vito, Aleš Holobar, Boštjan Simunič, Rado Pišot, Marco V Narici","doi":"10.1152/japplphysiol.00178.2025","DOIUrl":"10.1152/japplphysiol.00178.2025","url":null,"abstract":"<p><p>Previous studies showed that properties of higher-threshold motor units (MUs) and neuromuscular junction (NMJ) function are preserved during short-term disuse. This study aimed to test how a longer disuse period affects MU properties, NMJ transmission, and NMJ morphology remodeling. Nine young healthy males (age: 18-29 yr) underwent 21 days of horizontal bed rest. Pre- (BR0) and postbed rest (BR21), quadriceps maximal voluntary contraction (MVC), and size were assessed. We combined intramuscular electromyography (iEMG) and high-density surface electromyography (HDsEMG) recordings on the vastus lateralis to assess MU properties at 25% and 50% of MVC. Muscle biopsies and blood samples were also collected. Quadriceps MVC and size decreased at BR21. We found alterations in MU properties at both contraction intensities, including reduced discharge rate, MU potential area changes, and increased complexity. NMJ transmission was found to be reduced at BR21 at 25% MVC. This functional NMJ impairment was biochemically corroborated by an increase in serum C-terminal agrin fragment concentration, a biomarker of NMJ instability. In addition, a direct assessment of NMJ morphology revealed the presence of some denervated NMJs exclusively at BR21. In conclusion, 21-day bed rest altered MU properties across different contraction intensities and impaired NMJ transmission with initial signs of remodeling/denervation. Disuse duration appears to be a critical factor, as previous shorter studies failed to detect some of these changes. We believe these findings are clinically relevant for disuse after trauma, surgery, or illness and may support the development of effective countermeasures.<b>NEW & NOTEWORTHY</b> Leveraging both intramuscular and high-density surface EMG recordings in the vastus lateralis, we identified alterations in motor unit (MU) properties in young adults after 21 days of bed rest. These included reduced discharge rates and changes in MU potential size and complexity, observed at both low and moderate contraction intensities. Evidence of impaired neuromuscular junction (NMJ) function and denervation was also found. Our findings indicate that medium-term disuse elicits MU-level changes not detected in shorter-duration studies.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1411-1424"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019625","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}
Maria Bauer, Mahin Gadkari, Marta Martinez Yus, Lakshmi Santhanam, Jochen Steppan
{"title":"Sexual dimorphism in animal models of heart failure with preserved ejection fraction.","authors":"Maria Bauer, Mahin Gadkari, Marta Martinez Yus, Lakshmi Santhanam, Jochen Steppan","doi":"10.1152/japplphysiol.00595.2024","DOIUrl":"10.1152/japplphysiol.00595.2024","url":null,"abstract":"<p><p>Heart failure is a complex clinical syndrome that continues to be a leading cause of cardiovascular morbidity and mortality around the world. Despite major advances in its treatment and management, the rate of hospitalization and mortality has remained unchanged in the past decade. Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of all incident-based hospital admissions for decompensated heart failure and represents a global healthcare problem. Moreover, its incidence rate among all heart failures is increasing, and survival rates are significantly <50% at 5 years. Importantly, HFpEF disproportionately affects women after menopause, with female sex being independently associated with the prevalence of HFpEF and worse outcomes. The pathophysiology and critical molecular mechanisms underlying the progression of the abnormalities of this multifaceted syndrome are incompletely understood, and no evidence-based and target-directed treatment is available to prevent or cure its structural and functional myocardial dysfunction. To overcome this knowledge gap and develop targeted HFpEF therapies, animal models remain at the forefront of cutting-edge research studies. However, this is complicated by the lack of suitable animal models available that recapitulate the HFpEF phenotype in both sexes. This narrative review provides an overview of clinical features of the disease in both sexes and details carefully selected animal models with a particular focus on their ability to replicate sex-based differences.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1449-1473"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018112","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}
Priyanka Khemraj, Anastasiya Kuznyetsova, David A Hood
{"title":"Effect of aging, endurance training, and denervation on innate immune signaling in skeletal muscle.","authors":"Priyanka Khemraj, Anastasiya Kuznyetsova, David A Hood","doi":"10.1152/japplphysiol.00038.2025","DOIUrl":"10.1152/japplphysiol.00038.2025","url":null,"abstract":"<p><p>Skeletal muscle function relies on mitochondria for energy and for mediating its unique adaptive plasticity. The NLRP3 inflammasome complex is an innate immune mechanism that responds to mitochondrial damage-associated molecular patterns (DAMPs); however, its activity relative to mitochondrial dysfunction in muscle requires exploration. The purpose of this study was to characterize immune signaling and mitochondrial function in muscle during aging, endurance training, and disuse induced by denervation. Denervation led to decreases in muscle mass, mitochondrial content, and impaired respiration. Protein analyses revealed increases in NF-κB p65 and downstream inflammatory markers, including NLRP3, caspase-1, GSDMD-N, STING, and IL-1β, along with pro-apoptotic BAX and AIF. When assessing potential DAMPS, denervation led to increased ROS production but no changes in cytosolic mtDNA levels, relative to total mtDNA. Since we hypothesized that inflammasome activation would be increased with age, we studied young (6-8 mo) and aged (21-22 mo) mice that remained sedentary or underwent a 6-wk voluntary running protocol. Aging resulted in marked increases in the expression of multiple pro-inflammatory and pro-apoptotic proteins. Remarkably, training uniformly attenuated age-related increases in BAX, NLRP3, caspase-1, STING, and gasdermin-D (GSDMD) protein expression and tended to reduce the elevated level of cytosolic mtDNA evident in aged muscle. Training adaptations were also evident in the aged animals by the preservation of muscle mass and improvements in oxygen consumption and endurance performance, and were achieved despite a lower training distance than in young animals. Our results strongly implicate endurance training as a promising therapeutic for combating disuse and age-related inflammation in skeletal muscle.<b>NEW & NOTEWORTHY</b> This study aims to further elucidate the role between skeletal muscle activity, mitochondria, and innate immune signaling, specifically looking at the NLRP3 inflammasome complex. Our results demonstrate that disuse conditions such as aging and denervation were associated with a pro-inflammatory phenotype and impairments in mitochondrial functioning, whereas chronic endurance training demonstrated anti-inflammatory effects. Notably, this work highlights the benefits of exercise in attenuating age-related inflammation in aged skeletal muscle.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1341-1356"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997431","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}
Sydney E Hilton, Johan S Thiessen, Alise D Rycroft, Natalie I Miners, Julian C Bommarito, Tanvir S Matharu, Pardeep K Khangura, Rileigh K Stapleton, Leilani C Rocha, Massimo Nardone, Philip J Millar
{"title":"Influence of sex and aerobic fitness on blood pressure during maximal treadmill exercise in young healthy adults.","authors":"Sydney E Hilton, Johan S Thiessen, Alise D Rycroft, Natalie I Miners, Julian C Bommarito, Tanvir S Matharu, Pardeep K Khangura, Rileigh K Stapleton, Leilani C Rocha, Massimo Nardone, Philip J Millar","doi":"10.1152/japplphysiol.00056.2025","DOIUrl":"10.1152/japplphysiol.00056.2025","url":null,"abstract":"<p><p>Exaggerated exercise blood pressure (BP) is a predictor of future hypertension but commonly observed in athletes despite their reduced cardiovascular risk. Normalizing exercise BP to metabolic or mechanical work may provide better discrimination between physiological and pathological responses. This study investigated the effects of sex and aerobic fitness on peak systolic BP (SBP) and peak SBP per metabolic equivalent (SBP/MET slope). One hundred and eleven healthy adults (22 ± 5 years; 51 female) performed a graded maximal treadmill exercise test (modified Bruce protocol) with brachial BP measured using automated auscultation (Tango M2, SunTech Medical). Peak oxygen uptake rate (V̇o<sub>2peak</sub>) was assessed using indirect calorimetry. Males had a higher relative V̇o<sub>2peak</sub> (<i>P</i> < 0.01) but not V̇o<sub>2peak</sub> percentile (<i>P</i> = 0.16). Peak SBP was higher in males (208 ± 26 vs. 182 ± 23 mmHg, <i>P</i> < 0.01), while the SBP/MET slope did not differ between sexes (6.5 ± 2.4 vs. 6.3 ± 2.6 mmHg/MET, <i>P</i> = 0.60). Adjustment for differences in body mass index and V̇o<sub>2peak</sub> did not alter these results. The SBP-V̇o<sub>2peak</sub> regression slope did not differ between sexes (<i>P</i> = 0.92), with both slopes not different from zero (both, <i>P</i> > 0.47). The SBP/MET-V̇o<sub>2peak</sub> regression slope did not differ between sexes (<i>P</i> = 0.43), but both slopes were different from zero (both, <i>P</i> < 0.001). The present cohort demonstrated sex differences in peak SBP but not the SBP/MET slope. The SBP/MET slope was lower in individuals with higher aerobic fitness, but the influence of V̇o<sub>2peak</sub> did not differ between sexes. Using the SBP/MET slope in cross-sectional studies can reduce the confounding effects of sex on peak SBP, but differences in participant aerobic fitness should be considered.<b>NEW & NOTEWORTHY</b> Higher peak systolic blood pressure (SBP) during exercise is linked with an increased risk of developing hypertension. It has been suggested that exercise SBP should be normalized to mechanical or metabolic work to account for differences in aerobic fitness. We found that the influence of aerobic fitness on peak SBP or SBP per metabolic equivalent (SBP/MET slope) does not differ between sexes but that the SBP/MET slope is lower in participants with higher aerobic fitness.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1321-1326"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019630","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":"How much of HERstory is in the HIStory of the <i>Journal of Applied Physiology</i>?","authors":"Sushant M Ranadive, James M Hagberg","doi":"10.1152/japplphysiol.00950.2024","DOIUrl":"10.1152/japplphysiol.00950.2024","url":null,"abstract":"<p><p>Female underrepresentation in research has been a longstanding issue in clinical trials and health-related research. However, minimal data exist relative to this underrepresentation in physiology studies. To address this, we reviewed every article published in the <i>Journal of Applied Physiology</i> from 1948 to 2023. Articles were coded as human or animal study, or nonexperimental, and the number of female/male research participants, authors, and first/last authors. Across the <i>Journal of Applied Physiology</i>'s 75 yr, relative to human research studies the percentage of female research participants was 34% and the percentage of studies including female research participants was similar. Thus almost twice as many male research participants were studied (∼230,000 vs. ∼120,000), and there were twice as many studies including male compared to those including female research participants (10,318 vs. 5,138 studies). Furthermore, there were 10 times as many studies with only male versus only female research participants (5,757 vs. 559 studies). The percentage of female authors over the <i>Journal of Applied Physiology</i> history was 20% or four times more male authors compared to female authors (73,885 vs. 18,782 authors). The percentage of papers with female first/last authors was 28% or three times more male compared to female first/last authors (15,237 vs. 5,825 papers). All measures of female research participants and authors increased over the <i>Journal of Applied Physiology</i>'s history. However, the long-term outcome of the underrepresentation of female research participants and authors persists until the present. Thus <i>Journal of Applied Physiology</i> clearly has substantially less of HERstory than HIStory represented in its 75 yr of publication.<b>NEW & NOTEWORTHY</b> Females have been consistently underrepresented in the <i>Journal of Applied Physiology</i>, both as research participants and as manuscript authors. This study provides a comprehensive audit of the journal's publications from its inception in 1948 through the end of 2023 to examine these biological sex-related trends over time. Except for 2023, data reveal a persistent and significant gap in the inclusion of female participants and authors throughout the journal's history.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1327-1334"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998436","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":"Ketone ester ingestion impairs exercise performance without impacting cognitive function or circulating EPO during acute hypoxic exposure.","authors":"Myrthe Stalmans, Domen Tominec, Wout Lauriks, Ruben Robberechts, Monique Ramaekers, Tadej Debevec, Chiel Poffé","doi":"10.1152/japplphysiol.00097.2025","DOIUrl":"10.1152/japplphysiol.00097.2025","url":null,"abstract":"<p><p>Altitude-induced hypoxemia impairs exercise performance and cognition. Interestingly, ketone ester (KE) ingestion may attenuate hypoxemia, which likely explains the observation that KE impairs high-intensity exercise performance in normoxia but not in hypoxia. Moreover, KE was reported to attenuate cognitive decline at extreme altitudes (∼6,100 m). Given that hypoxemia is unaffected by KE in milder conditions, the impact of KE on cognition and performance in the absence of elevated oxygenation remains unknown. As KE may increase postexercise circulating [erythropoietin] ([EPO]) at sea level, we also assessed if KE might augment the blood [EPO] response after hypoxic exercise. In a double-blind, cross-over design, 13 healthy, male participants completed two 5.5-h sessions at 4,000-m simulated altitude while receiving either KE or placebo (CON). Throughout a graded exercise test (EX<sub>MAX</sub>) after 1.5 h, and a submaximal exercise bout (EX<sub>SUBMAX</sub>) after 3 h, blood and tissue oxygenation, ventilatory parameters, and acid-base balance were evaluated. Other measurements included cognitive function and blood [EPO]. KE reduced power output achieved during EX<sub>MAX</sub> by 3.6%, whereas blood and cerebral oxygenation were similar. KE ingestion lowered blood pH, [[Formula: see text]], pCO<sub>2</sub>, and [glucose], but did not impact cognitive function. In both KE and CON, circulating [EPO] increased by ∼56% after 5 h. These results indicate that KE ingestion impairs high-intensity exercise performance, at least if not compensated by elevated oxygenation. A progressively increasing oxygenation upon KE was unable to protect against hypoxia-induced cognitive declines and potentially counteracted a KE-induced augmentation of circulating [EPO].<b>NEW & NOTEWORTHY</b> This study is the first to show that KE ingestion impairs exercise performance in hypoxia, at least when KE does not alleviate hypoxemia. Despite a subsequent, progressive increase in oxygenation upon KE after 3-4 h, this does not protect against hypoxia-induced cognitive declines. Although studies in normoxia show potential of KE to increase blood [erythropoietin], we identified that KE ingestion fails to augment the increase in blood [erythropoietin] through hypoxic exposure and exercise.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1309-1320"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018110","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}
John Ashley, Evan P Pasha, Takashi Tarumi, Tsubasa Tomoto, Rong Zhang
{"title":"Lower diastolic velocity in the internal carotid artery mediates lower cerebral blood flow with age.","authors":"John Ashley, Evan P Pasha, Takashi Tarumi, Tsubasa Tomoto, Rong Zhang","doi":"10.1152/japplphysiol.00847.2024","DOIUrl":"10.1152/japplphysiol.00847.2024","url":null,"abstract":"<p><p>Advanced aging is characterized by reduced cerebral blood flow (CBF) and increased central arterial stiffness. Increased arterial stiffness is associated with increased CBF pulsatility, which is detrimental to cerebrovascular integrity. We examined the associations between central arterial stiffness, diastolic, systolic, and total CBF in healthy cognitively normal subjects (<i>n</i> = 163, age 20-81 yr, 62% female) who underwent color-coded duplex ultrasonography of the internal carotid (ICA) and the vertebral artery (VA) to measure pulsatile CBF and total CBF. Cerebral tissue oxygenation was measured using near-infrared spectroscopy (NIRS). Carotid β-stiffness index and carotid-femoral pulse wave velocity (cfPWV) were assessed via applanation tonometry and ultrasonography to assess central artery stiffness. Age was negatively associated with total CBF (<i>R</i><sup>2</sup> = 0.268, <i>P <</i> 0.001). ICA diastolic velocity was negatively associated with cfPWV (<i>R<sup>2</sup></i> = 0.163, <i>P <</i> 0.001) and carotid β-stiffness index (<i>R</i><sup>2</sup> = 0.134, <i>P <</i> 0.001). Higher carotid β-stiffness index was associated with lower CBF with age, which was mediated through lower ICA diastolic velocity. These findings suggest that central arterial stiffness with age may lead to reductions in ICA diastolic velocity, contributing to a reduction in CBF.<b>NEW & NOTEWORTHY</b> In this study, we demonstrated that higher central arterial stiffness is associated with lower diastolic velocity of the ICA, which mediates lower CBF with age. These findings provide new mechanistic insights into the reduction in CBF with age and add to the mounting evidence for the importance of age-related central arterial stiffening in brain health.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"1385-1397"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993866","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}