Zachary A Graham, Matthew P Bubak, Christiana J Raymond-Pope, Gary R Cutter, Jeremy S McAdam, S Craig Tuggle, Jacob A Siedlik, Luis G O de Sousa, Ed J Chappe, Kana Meece, Amritpal Kaur, Benny S R Ruiz, Sophia C Bamman, Katherine M Vanselow, Trevor W Perry, Jorge S Acosta-Arreguin, Natalie J Bohmke, Greg J Addison, J Michelle Bowers, Rachel L Wright, Lena D Fuentes, Jennifer E Smith, Karyn A Esser, Benjamin F Miller, Sue C Bodine, Marcas M Bamman
{"title":"Multidimensional Modeling to Maximize Adaptations to eXercise: The M<sup>3</sup>AX Trial Rationale and Study Design.","authors":"Zachary A Graham, Matthew P Bubak, Christiana J Raymond-Pope, Gary R Cutter, Jeremy S McAdam, S Craig Tuggle, Jacob A Siedlik, Luis G O de Sousa, Ed J Chappe, Kana Meece, Amritpal Kaur, Benny S R Ruiz, Sophia C Bamman, Katherine M Vanselow, Trevor W Perry, Jorge S Acosta-Arreguin, Natalie J Bohmke, Greg J Addison, J Michelle Bowers, Rachel L Wright, Lena D Fuentes, Jennifer E Smith, Karyn A Esser, Benjamin F Miller, Sue C Bodine, Marcas M Bamman","doi":"10.1152/japplphysiol.00486.2025","DOIUrl":"10.1152/japplphysiol.00486.2025","url":null,"abstract":"<p><p>Age-related functional declines are thought to be caused by hallmark biological processes that manifest in physical, mental, and metabolic impairments compromising intrinsic capacity, healthspan and quality-of-life. Exercise is a multipotent treatment with promise to mitigate most aging hallmarks, but there is substantial variability in individual exercise responsiveness. This inter-individual response heterogeneity (IRH) was first extensively interrogated by Bouchard and colleagues in the context of endurance training. Our group has interrogated IRH in response to resistance training and combined training, and we have conducted trials in older adults examining dose titration and adjuvant treatments in attempts to boost response rates. Despite the work of many groups, the mechanisms underpinning IRH and effective mitigation strategies largely remain elusive. The National Institute on Aging (NIA) hosted a focused workshop in 2022 titled \"Understanding heterogeneity of responses to, and optimizing clinical efficacy of, exercise training in old adults\". This workshop spurred a dedicated NIA request for applications (RFA) with the major goal \"to better understand factors underlying response variability to exercise training in older adults.\" We developed a two-phase Sequential Multiple Assignment Randomized Trial (SMART) in response to the RFA that will allow us to classify individual responsiveness to combined endurance and resistance training and interrogate potential mechanistic underpinnings (Phase I), followed by an approach to boost responsiveness (Phase II). Using deep in vivo, ex vivo, and molecular phenotyping, we will establish multidimensional biocircuitry of responsiveness and build predictive models, providing a basis for personalized exercise prescriptions.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182006","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":"Effects of riluzole on sevoflurane-induced gasping in adult mice.","authors":"Saki Taiji, Takashi Nishino, Hisayo Jin, Mayumi Hashida, Shiroh Isono","doi":"10.1152/japplphysiol.00347.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00347.2025","url":null,"abstract":"<p><p>The inhalation of a high sevoflurane concentration under hyperoxia induces gasping, similar to the breathing patterns observed during hypoxia-induced gasping in mice. This observation, coupled with the understanding that burster neurons in the pre-Bötzinger complex, which rely on a persistent sodium current, play a crucial role in generating hypoxia-induced gasping, led us to investigate whether sevoflurane-induced gasping could be triggered by activating this current within the brainstem. To this end, we evaluated the dose-dependent effects of intraperitoneal administration of riluzole, a blocker of persistent sodium channels, on sevoflurane-induced gasping in adult mice. Ten tracheally-intubated, spontaneously breathing, sevoflurane-anesthetized mice. Seven mice randomly received three doses of intraperitoneal riluzole (6, 12, 18 mg/kg, i.p.) with an interval of approximately four weeks. The test trials to elicit the sevoflurane-induced gasping were conducted before and after administering each dose of riluzole by a sudden rise in inspired concentration of sevoflurane from 0.8 MAC (2.5-2.7%) to 2 MAC (6.4-6.6%). In the other three mice, the test trials for eliciting the hypoxia-induced gasping were performed before and after administering 18 mg/kg riluzole. The administration of the increasing dose of riluzole demonstrated an apparent and dose-dependent attenuation of sevoflurane-induced gasping. The administration of 18 mg/kg of riluzole completely abolished the hypoxia-induced gasping. These results indicate that sevoflurane-induced gasping, like hypoxia-induced gasping, could be generated by activating persistent sodium current within the brainstem.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182070","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}
Pavel Vebr, Frantisek Galatík, Aneta Marvanova, Barbara Elsnicova, Daniela Hornikova, Marek Vecka, Sarka Spinova, Olga Novakova, Jitka M Zurmanova
{"title":"Long-term exposure to moderate cold reduces incidence of reperfusion tachyarrhythmias in rats.","authors":"Pavel Vebr, Frantisek Galatík, Aneta Marvanova, Barbara Elsnicova, Daniela Hornikova, Marek Vecka, Sarka Spinova, Olga Novakova, Jitka M Zurmanova","doi":"10.1152/japplphysiol.00509.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00509.2025","url":null,"abstract":"<p><p>Recently, moderate cold acclimation (9 °C; MCA) was found to exert cardioprotective effects by increasing resistance to ischemia-reperfusion (IR) injury and mitochondrial calcium overload in rats, but the effect of MCA on the incidence of IR arrhythmias is not known. The aim of this study was to determine whether MCA can induce an anti-arrhythmic effect and, if so, to elucidate a possible mechanism. Adult male Wistar rats were acclimated (9 °C) for short (1-3-10 days) and long-term (5 weeks; CA) periods, followed by a two-week recovery period (24 °C; CAR). The number of premature ventricular complexes (PVCs) and their duration after IR, western blotting, thin layer and gas chromatography were performed on left ventricular myocardium. We revealed that total reperfusion PVCs and tachyarrhythmia duration decreased even after CA, and accordingly the anti-arrhythmic n-3PUFAs increased in cardiac membrane phospholipids, the n-6/n-3 PUFA ratio decreased. CA increased the distribution of connexin 43 (Cx43) in favor of end-to-end junctions and the expression of uncoupling protein UCP3 in mitochondria. These beneficial effects were lost after two-weeks recovery period CAR. Interestingly, the mitochondrial antioxidants superoxide dismutase (SOD2) and thioredoxin reductase (TRXRD2) were strongly upregulated exclusively after 1 day of cold exposure, whereas cytosolic TRXRD1 was downregulated. In conclusion, long-term MCA (5-weeks) reduces the incidence of reperfusion arrhythmias, increases the proportion of anti-arrhythmic n-3PUFAs in cardiomyocyte membranes and has a positive effect on Cx43 distribution. By increasing the amount of UCP3 in mitochondria, it may reduce the likelihood of free radical formation in mitochondria during reperfusion.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130878","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":"The medial gastrocnemius fascicle shortening and tendon lengthening in static standing are associated with age-related postural instability in older adults.","authors":"Taku Miyazawa, Hiroki Hanawa, Keisuke Kubota, Keisuke Hirata, Tsutomu Fujino, Naohiko Kanemura","doi":"10.1152/japplphysiol.00431.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00431.2025","url":null,"abstract":"<p><p>Muscle-tendon unit (MTU) dynamics are involved in small body movements, including static standing. However, the effect of age-related reductions in tendon stiffness on static standing stability remains unclear. In this study, Achilles tendon stiffness was assessed in young and older adults, and muscle fascicle length and tendon length were measured during static standing with eyes open (EO) and eyes closed (EC) using ultrasonography. To isolate muscle-controlled activity, we analyzed intervals around the peak center of pressure (COP) velocity points. Fascicle length change (ΔL<sub>fas</sub>) and tendon length change (ΔL<sub>TS</sub>) during these intervals were calculated, compared by age group, and examined for their relationship to COP sway. COP was decomposed into rambling and trembling components, representing supraspinal and spinal-peripheral control processes, respectively. Results showed significantly reduced Achilles tendon stiffness and increased COP velocity and trembling in older adults (P=0.02, <0.001, and <0.001, respectively). Both age groups demonstrated fascicle shortening and tendon lengthening around peak COP velocity points, but changes were more pronounced in older adults, showing greater fascicle shortening and tendon elongation (age effect: P=0.012 and 0.031, respectively). ΔL<sub>fas</sub> amplitude positively correlated with COP velocity (EO: Young r=0.39, Older r=0.55; EC: Young r=0.71, Older r=0.44, all P<0.05) and trembling velocity (EO: Young r=0.49, Older r=0.56; EC: Young r=0.82, Older r=0.45, all P<0.001). These parameters, known to increase with age, are linked to co-contraction. This study demonstrates that excessive fascicle shortening, resulting from reduced tendon stiffness, contributes to increased postural sway in older adults.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130963","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}
Abid R Bhat, Awadhesh K Arya, Zuha Imtiyaz, Su Xu, Stephen R Thom
{"title":"Critical role for scavenger receptor CD36 in microparticle-mediated neuroinflammation in a murine model of decompression sickness.","authors":"Abid R Bhat, Awadhesh K Arya, Zuha Imtiyaz, Su Xu, Stephen R Thom","doi":"10.1152/japplphysiol.00484.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00484.2025","url":null,"abstract":"<p><p>Blood-borne microparticles (MPs) play a role in several forms of brain injury, but how they interact with the vasculature and contribute to neuroinflammation is unknown. The scavenger receptor CD36 is expressed across various cell types and regulates inflammation, vascular function, and innate immunity. We hypothesized that CD36 mediates MPs induced neuroinflammatory responses in a murine model of decompression sickness (DCS). Wild type mice subjected to decompression and naïve mice injected with MPs from decompressed mice exhibited a 2.2±0.5 fold elevation in perivascular MPs deposition, 2.8 ±0.6 fold elevation of inflammatory MPs in blood and 2.4 ±0.4 fold in cervical lymph nodes, 2.7 ± 0.6 fold increase in neutrophil activation, 2.0 ± 0.3-fold increased glymphatic flow, 3.1 ± 0.4 fold increased leakage of 6 megadalton dextran at the blood-brain barrier, and a doubling of inflammatory proteins in brain. These events failed to occur in CD36 knock-out mice and those conditionally deficient in endothelial CD36 (FLOX). We conclude that inflammatory MPs interact with endothelial CD36 to mediate neuroinflammatory responses and vascular injury in DCS.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130934","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}
Viet Q Dinh, Malinda Hansen, K Austin Davis, Lindsey Peralez, Caroline A Rickards
{"title":"Acute cardiovascular and cerebral blood flow responses to high frequency, low amplitude vibration on the neck.","authors":"Viet Q Dinh, Malinda Hansen, K Austin Davis, Lindsey Peralez, Caroline A Rickards","doi":"10.1152/japplphysiol.00328.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00328.2025","url":null,"abstract":"<p><p>Local muscle vibration (LMV) is a potential therapeutic approach to treat symptoms related to stroke by improving muscle function and blood flow. In this study, we assessed the acute cardiovascular and cerebral blood flow responses to LMV when applied to the anterior neck muscles in young and healthy participants. We hypothesized that LMV would elicit minimal acute cardiovascular responses. Ten human participants (5 male, 5 female) underwent LMV on both sides of their neck for 5-min each. Arterial pressure, middle cerebral artery blood velocity (MCAv), and common carotid artery (CCA) blood flow were measured continuously. There was no effect of LMV on <b>mean arterial pressure</b> (RIGHT, Baseline: 96.9±4.9 mmHg vs. LMV: 97.8±5.7 mmHg vs. Recovery: 98.2±4.6 mmHg, P=0.25; LEFT, Baseline: 96.0±7.8 mmHg vs. LMV: 97.0±7.7 mmHg vs. Recovery: 97.9±7.5 mmHg; P=0.23) or <b>MCAv</b> (RIGHT, Baseline: 61.4±10.5 cm/s vs. LMV: 62.0±10.7 cm/s vs. Recovery: 59.3±9.7 cm/s; P=0.15; LEFT, Baseline: 59.9±10.2 cm/s vs. LMV: 60.6±10.8 cm/s vs. Recovery: 58.4±10.2 cm/s; P=0.20). <b>CCA diameter</b> increased slightly with LMV on both sides of the neck (RIGHT, Baseline: 6.2±0.6 mm vs. LMV: 6.3±0.7 mm, P=0.03; LEFT, Baseline: 6.4±0.5 mm vs. LMV: 6.5±0.5 mm, P=0.03). However, this did not affect <b>CCA blood flow</b> (RIGHT, Baseline: 330.7±68.5 ml/min vs. LMV: 324.7±57.6 ml/min, P=0.59; LEFT, Baseline: 358.1±67.5 vs. LMV: 344.2±78.3 ml/min, P=0.30). These data provide evidence that a single acute session of LMV does not affect key cardiovascular parameters in young and healthy participants.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130918","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}
Antonis Elia, Mikael Gennser, Ola Eiken, Michail E Keramidas
{"title":"Systemic and regional hemodynamic and (de)oxygenation responses across repeated breath-holds.","authors":"Antonis Elia, Mikael Gennser, Ola Eiken, Michail E Keramidas","doi":"10.1152/japplphysiol.00508.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00508.2025","url":null,"abstract":"<p><p><b>Introduction:</b> Regional cerebral and peripheral tissue (de)oxygenation responses to breath-holding (apnea) have predominantly been examined during isolated attempts. How these responses evolve across repeated efforts remains unclear, as previous studies either averaged data across bouts or focused solely on the final repetition. Accordingly, this study mapped the (de)oxygenation dynamics across successive breath-holds. <b>Methods:</b> Fifteen non-divers performed three repeated maximal static breath-holds, separated by two-minute rest-intervals. Systemic cardiovascular variables, gas exchange, and cerebral frontal-cortex and forearm-muscle (de)oxygenation were assessed. <b>Results:</b> At each breath-hold onset, a transient fall in cerebral oxygenated hemoglobin (cO<sub>2</sub>Hb) and arterial pressure occurred, coinciding with tachycardia. A cardiovascular steady state followed which persisted until the onset of involuntary breathing movements (IBMs). At IBM onset, cO<sub>2</sub>Hb increased only during the first attempt (Δ8±5μM,p<0.001), with smaller changes in subsequent breath-holds (apnea-2,Δ3±6μM;apnea-3,Δ3±5μM,p≤0.014). Cerebral deoxygenated hemoglobin (cHHb) increased progressively across breath-holds (apnea-1,Δ3±4μM;apnea-2,Δ5±4μM;apnea-3,Δ7±5μM,p≤0.001), whereas arterial pressure increases were of similar magnitude (p≥0.064). Forearm (de)oxygenation profiles were comparable across attempts (p≥0.085). In 9 subjects, a triphasic peripheral response emerged: initial rapid decline in O<sub>2</sub>Hb and rise in HHb at breath-holding onset, a transient intermediate-plateau, and further divergence near IBM onset. Breath-holds were terminated at successively lower cO<sub>2</sub>Hb, cerebral tissue oxygen index, and end-tidal oxygen, and higher cHHb (p≤0.034), but similar end-tidal carbon dioxide levels (p>0.912). <b>Conclusion:</b> The magnitude and timing of regional (de)oxygenation responses vary greatly over repeated breath-holds. Cerebral oxygenation showed a pronounced increase during the first attempt, but progressively smaller changes across subsequent bouts. In contrast, peripheral tissue oxygenation, demonstrated a time-dependent decline across successive attempts.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130928","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":"Edward F. Adolph Distinguished Lecture: Protein & Energy Metabolism - A State of Flux.","authors":"Benjamin F Miller","doi":"10.1152/japplphysiol.00762.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00762.2025","url":null,"abstract":"<p><p>Physiology processes are integrated, dynamic, and periodic, and thus benefit from methods that capture their dynamic nature. Since we are often limited to discrete sampling points in physiological studies, many methods provide snapshots of a system. However, these snapshots can at times be limited in their ability to understand the underlying events. This article is a summary of my 2025 Adolph Lecture and discusses how tracers (particularly, stable isotopes) go beyond mere snapshots to provide important insight into dynamic events. The article is part review and part narrative that provides insight into my scientific journey and the thought process that went into the design of the highlighted studies. I primarily feature articles published in APS journals and note what insight the tracer-based measurements provide. I hope that the reader comes away with an appreciation of the complexity of physiological studies and why tracer-based studies are in fact mechanistic.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124516","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}
Nicole V Bushfield, Nicole A Johnson, Jessica A Dickenson, Benjamin W L MacKenzie, Rodion Isakovich, Anne Kalker, Janne Bouten, Nicholas D J Strzalkowski, Taylor S Harman, Pontus Holmström, Ajaya J Kunwar, Nilam Thakur, Sunil Dhungel, Nima Sherpa, Abigail W Bigham, Tom D Brutsaert, Trevor A Day
{"title":"No Altitude Required: Differential ventilatory and blood acid-base homeostasis between unacclimatized lowlanders and Tibetan highlanders at 1,400 m.","authors":"Nicole V Bushfield, Nicole A Johnson, Jessica A Dickenson, Benjamin W L MacKenzie, Rodion Isakovich, Anne Kalker, Janne Bouten, Nicholas D J Strzalkowski, Taylor S Harman, Pontus Holmström, Ajaya J Kunwar, Nilam Thakur, Sunil Dhungel, Nima Sherpa, Abigail W Bigham, Tom D Brutsaert, Trevor A Day","doi":"10.1152/japplphysiol.00619.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00619.2025","url":null,"abstract":"<p><p>Tibetan highlanders (TH) possess physiological adaptations supporting ventilation, oxygenation, and acid-base regulation with acclimatization to chronic hypobaric hypoxia. While well-characterized at high-altitude, it is unclear whether these traits are evident at low-altitude, independent of environmental hypoxic stimuli. To evaluate baseline physiological differences, we compared variables related to ventilatory, blood oxygen, and acid-base balance between unacclimatized ancestral lowlanders (LL; n=29) and TH (n=31) residing at 1,400 m, a subthreshold altitude not expected to elicit ventilatory or renal acclimatization. Heated hand capillary blood samples were analyzed for hemoglobin ([Hb]<sub>c</sub>), oxygen content (C<sub>c</sub>O<sub>2</sub>), alveolar ventilation (V̇<sub>A</sub>), steady-state chemoreflex drive (SSCD), partial pressure of carbon dioxide (P<sub>c</sub>CO<sub>2</sub>), bicarbonate ([HCO<sub>3</sub><sup>-</sup>]<sub>c</sub>), and pH<sub>c</sub>. TH demonstrated significantly higher V̇<sub>A</sub> (4.6±0.4 vs. 4.8±0.3 l/min; +5.2%; P=0.0101) and SSCD (11.9±1.9 vs. 13.2±1.9 a.u.; +10.3%; P=0.0127) than LL, despite equivalent SpO<sub>2</sub> (P=0.8882). Additionally, TH exhibited lower P<sub>c</sub>CO<sub>2</sub> (37.9±2.8 vs. 36.0±2.5 mmHg; -5%; P=0.0086) and [HCO<sub>3</sub><sup>-</sup>]<sub>c</sub> (22.9±1.4 vs. 21.5±1.6 mmol/l; -6.1%; P=0.0007) compared to LL, with no difference in pH<sub>c</sub> (P=0.256).The reduction of [HCO<sub>3</sub><sup>-</sup>]<sub>c</sub> in TH was greater than expected from passive chemical buffering alone, suggesting differential renal handling breathing ambient air at low altitude. These findings suggest that TH maintain a distinct ventilatory and acid-base homeostatic set-point at low altitude, characterized by enhanced resting ventilatory drive and renal excretion of HCO<sub>3</sub><sup>-</sup>. These traits, characterized at low altitude, suggest that developmental exposure to hypoxia and/or Tibetan ancestry is associated with developed or evolved physiological traits that optimize respiratory and acid-base homeostasis during high-altitude ascent.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080833","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}
Miles F Bartlett, Andrew P Oneglia, Delaney Davis, Sauyeh Zamani, Ashfaq Siddiqui, Mark D Ricard, Michael D Nelson
{"title":"Maximal-effort knee-extension exercise impairs skeletal muscle oxidative capacity and VO<sub>2</sub> recovery <i>in vivo</i>.","authors":"Miles F Bartlett, Andrew P Oneglia, Delaney Davis, Sauyeh Zamani, Ashfaq Siddiqui, Mark D Ricard, Michael D Nelson","doi":"10.1152/japplphysiol.00517.2025","DOIUrl":"https://doi.org/10.1152/japplphysiol.00517.2025","url":null,"abstract":"<p><p>In the present study, we examined how fatiguing exercise affects O<sub>2</sub>-based measures of skeletal muscle oxidative capacity <i>in vivo</i> by measuring changes in the rate constant of muscle VO<sub>2</sub> recovery (<i>k</i><sub>VO2</sub>). Healthy young adults completed isokinetic (120º∙s<sup>-1</sup>), maximal voluntary dynamic contractions (MVDCs) lasting 24- (baseline <i>k</i><sub>VO2</sub>) and 240 s (post-fatiguing exercise <i>k</i><sub>VO2</sub>). Vastus lateralis <i>k</i><sub>VO2</sub> was measured using near-infrared diffuse correlation spectroscopy (NIRS-DCS) via the conventional repeated arterial occlusion method (Part-A, n=14) or a novel NIRS-DCS 'free-flow' method (Part-B, n=13). Pulmonary VO<sub>2</sub> (pVO<sub>2</sub>), muscle VO<sub>2</sub> (mVO<sub>2</sub>), and surface electromyography (sEMG) measures of muscle activation were also measured throughout the 240-s trial. Compared to the 24-s trial, <i>k</i><sub>VO2</sub> following 240s of MVDCs was impaired by ~25% (Part-A; p=0.005) and ~16% (Part-B; p=0.017). Moreover, both pVO<sub>2</sub> and mVO<sub>2</sub> rapidly increased to maximal levels, where they remained for the duration of the 240-s trial, despite sEMG activity and peak MVDC power declining. These results demonstrate that fatiguing exercise not only impairs O<sub>2</sub>-based measures of skeletal muscle oxidative capacity, but that mitochondrial O<sub>2</sub>-consumption is uncoupled from power output and ATP demand during fatiguing exercise.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080830","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}