{"title":"Effect of short-term high-altitude acclimatization on the relationship between cerebral blood flow and symptoms of mild acute mountain sickness in males.","authors":"Kazunobu Okazaki, Katsumi Asano, Masahiro Horiuchi","doi":"10.1152/japplphysiol.00434.2024","DOIUrl":"10.1152/japplphysiol.00434.2024","url":null,"abstract":"<p><p>People who climb high altitudes frequently experience headaches, which are the primary symptoms of acute mountain sickness (AMS). Although headaches and AMS are primarily caused by hypoxia, they remain poorly understood, specifically, the effects of regional cerebral blood flow on headache and AMS. In this high-altitude laboratory study, we investigated the hypothesis that regional cerebrovascular responses to high-altitude (3,776 m) sojourns are associated with AMS symptoms. The internal carotid artery (ICA), vertebral artery (VA), cardiorespiratory and vascular responses, and symptoms of AMS were assessed in eight healthy male lowlanders (mean age, 34 yr) at sea level (SL, 450 m) and on three consecutive days at the summit of Mount Fuji (3,776 m). Compared with sea level, ICA flow increased on <i>day 3</i> (<i>P</i> = 0.009) and ICA diameter increased on <i>days 1</i>-<i>3</i> (<i>P</i> < 0.001). In contrast, VA flow increased on <i>days 1</i> and <i>2</i> (<i>P</i> = 0.008 and <i>P</i> = 0.018, respectively) and VA velocity increased on <i>day 1</i> (<i>P</i> = 0.044). Headaches increased over the 3 days (<i>P</i> = 0.011 to <i>P</i> = 0.048), but AMS increased on <i>day 3</i> (<i>P</i> = 0.001). Repeated-measures correlation analysis revealed that changes in headaches from the previous day were correlated with percent changes in ICA diameter (<i>r</i><sub>rm</sub> = 0.596, <i>P</i> = 0.012), VA flow, and velocity (<i>r</i><sub>rm</sub> = 0.537, <i>P</i> = 0.026 and <i>r</i><sub>rm</sub> = 0.619, <i>P</i> = 0.008, respectively). Thus, a high-altitude-induced increase in cerebrovascular perfusion may contribute to the worsening of headaches, which is a typical AMS pathogenesis.<b>NEW & NOTEWORTHY</b> Acute mountain sickness (AMS) symptoms for 3 days at 3,776 m were assessed using volumetric cerebral blood flow. Internal carotid arterial (ICA) flow increased gradually, whereas vertebral arterial (VA) flow acutely increased on <i>day 1</i> but decreased thereafter. Headaches increased over 3 days, but AMS did not until <i>day 3</i>. Changes in headaches were correlated with those in ICA diameter and VA flow/velocity. Thus, a high-altitude-induced increase in cerebrovascular perfusion may contribute to worsening headaches.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"571-581"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764948","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}
Auni C Williams, Virginia G Content, Raegan E Atha, Arpit Davé, Kristin Riley, Lacy M Alexander
{"title":"Longitudinal measurements of NO-mediated vasodilation and physical activity over 1 yr following endometriosis excision surgery: a passive experiment.","authors":"Auni C Williams, Virginia G Content, Raegan E Atha, Arpit Davé, Kristin Riley, Lacy M Alexander","doi":"10.1152/japplphysiol.00297.2025","DOIUrl":"10.1152/japplphysiol.00297.2025","url":null,"abstract":"<p><p>Women with endometriosis are at increased risk of cardiovascular disease and demonstrate endothelial dysfunction. The gold standard for diagnosis of endometriosis is through operative laparoscopy with surgical excision and histopathologic identification of endometrial-type glands and stroma. Symptoms of endometriosis are often immediately improved or resolved following excision surgery, but the cardiovascular impact of excision surgery is underappreciated. This passive experiment reports the longitudinal adaptations of the macrovascular and cutaneous microvascular endothelium in a single patient following surgical excision of endometriosis. The patient participated in multiple vascular research studies targeting nitric oxide-mediated vasodilation over the course of the succeeding 13 mo postsurgery. We show no nitric oxide (NO)-mediated vasodilation in the microvascular endothelium [-34 arbitrary units (AU)] and no flow-mediated dilation (FMD) in the brachial conduit artery (-0.06%) 1-mo postsurgery, with a recovery seeming to occur ∼8 mo postsurgery (178 AU, 3.69% FMD) that does not remain ∼13 mo postsurgery (3 AU, 0.43%). These values occur in tandem with reported exercise before testing [1,746 to 3,759 to 1,954 metabolic equivalent (MET) min/wk, respectively]. The results of these studies, placebo and baseline visits, are presented here. These findings suggest that microvascular endothelial function in an otherwise healthy young woman with endometriosis is not necessarily recovered following excision surgery, but may be dramatically improved with resistance exercise. Our data may lend insight into the progression of vascular dysfunction in this disease and the role of surgical versus lifestyle intervention in this realm.<b>NEW & NOTEWORTHY</b> This passive experiment demonstrates that vascular endothelial function is not recovered following endometriosis surgery but may be improved with resistance exercise.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"438-443"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Casey L Sexton, Selene Meza-Perez, Konstantinos Papanikolaou, Tomasz M Kaminski, Marta Nowacka-Chmielewska, Piotr Rodak, Yi Lin, Thomas W Buford, Peter E Morris, Davis A Englund, Robert T Mankowski
{"title":"The role of adipose tissue in critical illness-induced skeletal muscle wasting-new considerations for treatment approaches.","authors":"Casey L Sexton, Selene Meza-Perez, Konstantinos Papanikolaou, Tomasz M Kaminski, Marta Nowacka-Chmielewska, Piotr Rodak, Yi Lin, Thomas W Buford, Peter E Morris, Davis A Englund, Robert T Mankowski","doi":"10.1152/japplphysiol.00203.2025","DOIUrl":"10.1152/japplphysiol.00203.2025","url":null,"abstract":"<p><p>Critical illness-induced muscle wasting is associated with poor in-hospital and long-term outcomes, but prevention strategies are lacking. Critical illness elicits muscle wasting through upregulation of protein degradation and downregulation of protein synthesis via primary (i.e., modulation of ubiquitin-proteasome, autophagy-lysosome, calpain, and caspase-3 pathways) and secondary (i.e., bed rest/disuse, nutritional modulation, and accumulation of cellular damage) mechanisms. However, therapeutic targeting of these skeletal muscle mechanisms has not advanced the prevention of critical illness-induced muscle wasting, which may require exploring the roles of other peripheral organs. For example, recent research has demonstrated positive associations between whole-body adipose tissue mass, maintenance of muscle mass, and lower mortality rates in critically ill patients. However, having excess adiposity is often associated with impaired skeletal muscle remodeling due to blunted anabolic signaling, which has been tied to insulin resistance, lipid accumulation, and inflammation. Thus, the positive association between adiposity and beneficial outcomes in critical illness is paradoxical. This may be explained, at least partially, by an incomplete understanding of the processes by which adipose tissue influences skeletal muscle health and function in the context of critical illness. This review highlights the current evidence and key questions that warrant further investigations to improve understanding of the relationship between adipose tissue and skeletal muscle health. This knowledge may then be leveraged to facilitate new therapeutic approaches aimed at improving skeletal muscle health and functional outcomes in patients with critical illness.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"414-437"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528125","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}
Joshua B Currens, Richard E Moon, Matthew S Makowski, Michael J Natoli, Jayne Leypoldt, Jean Woolard, David Brown, Arian Azarang, Robert Brown, Eric Schinazi, Zach Ransom, Virginie Papadopoulou, Rachel M Lance
{"title":"Ultrasound detection of lymphatic bubbles in a porcine dive model.","authors":"Joshua B Currens, Richard E Moon, Matthew S Makowski, Michael J Natoli, Jayne Leypoldt, Jean Woolard, David Brown, Arian Azarang, Robert Brown, Eric Schinazi, Zach Ransom, Virginie Papadopoulou, Rachel M Lance","doi":"10.1152/japplphysiol.00171.2025","DOIUrl":"10.1152/japplphysiol.00171.2025","url":null,"abstract":"<p><p>Ultrasound is currently the optimal imaging modality in the decompression research field for assessing intracorporeal gas. Decompression sickness (DCS) is triggered by excess gas bubble presence in the body; however, the relationship is not well understood. Presently, the decompression physiology field does not have a strong predictive DCS biomarker. In this study, we explore the presence of lymph node decompression bubbles in a porcine model after a provocative hyperbaric exposure. Porcine test subjects (<i>n</i> = 37 subjects) underwent an aggressive decompression profile as part of a larger study, and a subsequent investigation of the left inguinal lymph node was conducted with ultrasound. Ultrasound images were assessed by three trained sonographers for lymph node bubbles. Regional brightness was analyzed after post hoc phantom-calibrated standardization of ultrasound depth and gain settings. Out of the 37 animals that we examined for lymph node bubbles, 17 were diagnosed with severe DCS and 14 identified to have lymph node bubbles. A postmortem dissection was conducted for a few animals, and bubbles could be found streaming from the lymph node corresponding to a severe DCS subject. The brightness assessment of the standardized ultrasound images indicated that DCS cases typically had a decrease in the region intensity after the dive with a potential peak sensitivity of 94.1% and specificity of 55% based on receiver-operating curve analysis. This study is the first noninvasive detection of lymph node decompression bubbles with confirmation of bubbles by postmortem dissection. A positive correlation between lymph node bubbles and DCS severity was found.<b>NEW & NOTEWORTHY</b> This is the first ever study to noninvasively detect lymphatic decompression bubbles and examine their correspondence with severe decompression sickness (DCS) outcome. The image brightness analysis found that subjects with severe DCS were likely to have darker lymph node images postdive indicating potential gas presence, after variable ultrasound system settings were unified post hoc. These findings may provide an early framework for a wearable ultrasound device to monitor real-time decompression stress.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"365-375"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528126","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}
Matthew J McDonald, Sharon D Fears, Samuel A Martin, Brian Shariffi, Todd L Lancaster, Jill A Kanaley, Jacqueline K Limberg
{"title":"Resveratrol restores indices of neurovascular coupling following acute sleep restriction in young men and women.","authors":"Matthew J McDonald, Sharon D Fears, Samuel A Martin, Brian Shariffi, Todd L Lancaster, Jill A Kanaley, Jacqueline K Limberg","doi":"10.1152/japplphysiol.00402.2025","DOIUrl":"10.1152/japplphysiol.00402.2025","url":null,"abstract":"<p><p>Acute sleep restriction (4 h time in bed) impairs the link between neural activity and cerebral blood flow (i.e., neurovascular coupling, NVC). Nitric oxide (NO) is an important mechanism in the NVC response. Insufficient sleep increases reactive oxygen species (ROS) and reduces NO bioavailability. Resveratrol, a polyphenol with antioxidant properties, reduces ROS and improves vascular function. We hypothesized that NVC following acute sleep restriction would be improved with acute oral resveratrol supplementation. Sixteen adults (8 M/8 F, age: 28 ± 7 yr, 25 ± 3 kg/m<sup>2</sup>) completed two morning visits following a night of normal (NS; 449 ± 46 min) or restricted (RS; 243 ± 12 min) sleep. During each visit, middle (MCAv) and posterior (PCAv) cerebral artery velocity (transcranial Doppler ultrasound) were measured before and 45 min following oral resveratrol (250 mg) during: <i>1</i>) a validated visual search paradigm (Where's Waldo) and <i>2</i>) 5-min carbogen (95% O<sub>2</sub>, 5% CO<sub>2</sub>) air breathing. The peak cerebral blood velocity response to visual stimulation was reduced following sleep restriction (MCAV: NS 16 ± 7%, RS 11 ± 7%, <i>P</i> = 0.017; PCAv: NS 43 ± 13%, RS 32 ± 14%, <i>P</i> = 0.017) and restored with resveratrol in the PCA (RS + resveratrol: 40 ± 17%; <i>P</i> = 0.028), but not the MCA (RS + resveratrol: 9 ± 5%; <i>P</i> = 0.391). There was no effect of oral resveratrol on the peak response to visual stimulation following normal sleep. There was no effect of sleep restriction nor oral resveratrol on cerebrovascular response to carbogen air breathing. One night of RS (4 h time in bed) impairs NVC and resveratrol mitigates this impairment, particularly in the PCA. These results enhance our mechanistic understanding of sleep-associated impairments in NVC.<b>NEW & NOTEWORTHY</b> Herein, we demonstrate that one night of restricted sleep (4 h time in bed) impairs the link between neural activity and cerebral blood flow (i.e., neurovascular coupling, NVC) of both middle and posterior cerebral arteries, and oral resveratrol supplementation may mitigate these impairments, particularly in the posterior cerebral artery. These results enhance our mechanistic understanding of sleep-associated impairments in NVC and advance our knowledge of neurovascular dysfunction occurring after restricted sleep.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"376-383"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560232","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}
Virginia R Nuckols, Kristen G Davis, Meaghan Smith, Mariah L Carey, Blair Bell, Mark K Santillan, Donna A Santillan, Gary L Pierce
{"title":"Association of physical activity, sedentary time, and sleep with maternal vascular function in women with a history of preeclampsia.","authors":"Virginia R Nuckols, Kristen G Davis, Meaghan Smith, Mariah L Carey, Blair Bell, Mark K Santillan, Donna A Santillan, Gary L Pierce","doi":"10.1152/japplphysiol.00928.2024","DOIUrl":"10.1152/japplphysiol.00928.2024","url":null,"abstract":"<p><p>A history of preeclampsia (hxPE) is associated with persistent vascular dysfunction and elevated risk of chronic hypertension. Twenty-four-hour activity behaviors, including physical activity, sedentary time (SED), and sleep, are modifiable factors that may promote favorable vascular function and blood pressure in women with a hxPE. The primary objective of this study was to investigate the cross-sectional relations between habitual physical activity, SED, and sleep with aortic stiffness and 24-h blood pressure patterns in young women with a hxPE and healthy pregnancy controls. Participants (<i>n</i> = 68; aged 21-42 yr, 1-5 yr after delivery) wore a thigh-mounted activity monitor (activPAL) for 7 days and maintained a sleep log to assess habitual physical activity, SED, and sleep duration. Participants underwent measures of aortic stiffness (measured by carotid-femoral pulse wave velocity, CFPWV) and 24-h ambulatory blood pressure monitoring (ABPM). Women with a hxPE (<i>n</i> = 33) did not differ in physical activity, SED, or sleep compared with healthy pregnancy controls (<i>n</i> = 35). SED (β = 0.214, 95CI [0.004, 0.416]) and light-intensity physical activity (β = -0.204, 95CI [-0.397, -0.004]) were independently related to CFPWV. Frequency of sleep disturbances, but not shorter sleep duration, was associated with higher 24-h diastolic blood pressure (β = 0.258, 95CI [0.009, 0.525]). Select perceived benefits and barriers to exercise were more pronounced among women with hxPE, and benefits were associated with higher moderate-vigorous physical activity (ρ = 0.43, <i>P</i> = 0.003). Our findings link habitual activity, pregnancy history, and perceived exercise benefits with aortic stiffness and identify population and behavioral targets to improve cardiovascular health in young parous women.<b>NEW & NOTEWORTHY</b> Preeclampsia is associated with persistent vascular dysfunction and incident hypertension, but the contributing behavioral factors are unclear. We demonstrate that greater light-intensity physical activity and lower sedentary time are associated with lower aortic stiffness, and link sleep disturbances to 24-h blood pressure among women with a recent history of preeclampsia and healthy pregnancy controls. Time spent in light intensity activity and sedentary behavior may represent interventional targets to mitigate elevated cardiovascular risk in postpartum women.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"384-393"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marcela S Araújo, Adamor S Lima, Rosa V D Guerrero, Lauro C Vianna
{"title":"Central command activation during exercise is an essential mechanism to sustain diving bradycardia.","authors":"Marcela S Araújo, Adamor S Lima, Rosa V D Guerrero, Lauro C Vianna","doi":"10.1152/japplphysiol.00274.2025","DOIUrl":"10.1152/japplphysiol.00274.2025","url":null,"abstract":"<p><p>Previous studies have shown that the bradycardic response to diving is maintained or enhanced during exercise. However, the integrative mechanism by which diving-induced bradycardia supersedes exercise-induced tachycardia remains unclear. This study aimed to elucidate the contributions of central and peripheral afferent mechanisms to the diving response in humans under controlled laboratory conditions. Thirty-two healthy participants [17 males, 15 females; mean age: 22 ± 3 yr; body mass index (BMI): 24 ± 4 kg/m<sup>2</sup>] were exposed to simulated diving via trigeminal nerve stimulation (TGS) under three experimental conditions: <i>1</i>) voluntary light (LEx) and moderate (MEx) leg cycling exercise, <i>2</i>) passive exercise and the cold pressor test (CPT), and <i>3</i>) a combination of voluntary exercise and CPT. Continuous beat-to-beat heart rate (HR) and arterial blood pressure were measured, with surface electromyography confirming the absence of voluntary muscle contractions during passive cycling. TGS elicited significant bradycardia at rest, and this response was increased during voluntary LEx, and preserved during voluntary MEx when compared with rest. In contrast, compared with rest, the HR response to TGS during passive exercise was significantly attenuated, whereas CPT completely abolished the bradycardic response to TGS. However, during LEx combined with CPT, TGS elicited a significant bradycardic response when compared with CPT alone. Overall, these findings suggest that <i>1</i>) central command activation is an essential mechanism for sustaining the diving bradycardia; <i>2</i>) isolated peripheral afferent reflexes exert inhibitory feedback to regulate diving-induced bradycardia; and <i>3</i>) central and peripheral afferent feedback are important mechanisms by which volitional skeletal muscle contractions modulate the cardiovascular adjustments to \"diving.\"<b>NEW & NOTEWORTHY</b> Diving triggers conflicting heart rate control pathways: the diving response induces bradycardia, whereas muscular contraction engages neural signals that can cause tachycardia. Although bradycardia persists during exercise, the mechanisms by which diving-induced bradycardia overrides exercise-induced tachycardia are unclear. Our findings show that central command activation is essential for sustaining diving bradycardia, whereas peripheral afferent reflexes provide inhibitory feedback. These results advance our understanding of cardiovascular adaptations to diving, with implications for marine biology and exercise physiology.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"355-364"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528121","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}
Francesca Gelpi, Beatrice Cairo, Vlasta Bari, Beatrice De Maria, Angela S M Salinet, Man Y Lam, Osian Llwyd, Jonathan Ince, Jatinder S Minhas, Ronney B Panerai, Alberto Porta
{"title":"Cerebrovascular variability interactions after acute ischemic stroke: insights from directionality analysis based on transfer entropy.","authors":"Francesca Gelpi, Beatrice Cairo, Vlasta Bari, Beatrice De Maria, Angela S M Salinet, Man Y Lam, Osian Llwyd, Jonathan Ince, Jatinder S Minhas, Ronney B Panerai, Alberto Porta","doi":"10.1152/japplphysiol.00250.2025","DOIUrl":"10.1152/japplphysiol.00250.2025","url":null,"abstract":"<p><p>Dynamic cerebral autoregulation (CA) limits fluctuations of mean cerebral blood flow, approximated as mean cerebral blood velocity (MCBv) measured via transcranial Doppler ultrasound, in the presence of variations of mean arterial pressure (MAP). This mechanism is impaired after acute ischemic stroke (AIS). CA impairment is usually assessed by hypothesizing that MAP variations are completely responsible for MCBv changes, although disregarding the MCBv contributions to MAP variability. We exploited transfer entropy (TE) and conditional TE (CTE) to assess the strength of the directional interactions from MAP to MCBv and vice versa accounting for partial pressure of end-tidal carbon dioxide. Traditional markers were computed for comparison. We analyzed recordings from 34 control individuals (CTRL, age: 66 ± 7 yr) and 48 patients with AIS (age: 66 ± 13 yr) acquired within 48 h of stroke symptom onset. MCBv was recorded in both hemispheres including affected and unaffected hemispheres in patients with AIS. Patients with AIS exhibited hypertension and hypocapnia. After AIS MCBv diminished, especially in the affected hemisphere. TE and CTE decreased along the pressure-to-flow pathway as well. Both directional markers tend to increase along the flow-to-pressure arm irrespective of the hemisphere. Traditional indexes could not detect any difference. Our analysis suggests that the CA impairment was characterized by an imbalance of information transfer within the MCBv-MAP closed loop with a reduced importance of the pressure-to-flow and increased relevance of the flow-to-pressure arm. The study stresses the relevance of assessing MCBv-MAP relationship in closed loop, especially when variability of MAP and MCBv are considered.<b>NEW & NOTEWORTHY</b> The study emphasizes the importance of understanding the closed-loop relationship between mean arterial pressure and mean cerebral blood velocity when characterizing cerebrovascular control. Directional analysis is particularly insightful in acute ischemic stroke because modifications occurring along the flow-to-pressure link complement the ones derived from the more traditionally examined pressure-to-flow pathway.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"341-354"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528122","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":"Reliability of using the skin blood flow plateau response to local heating as a noninvasive assessment of nitric oxide-dependent vasodilation.","authors":"Brett J Wong, Matthew J Hayat","doi":"10.1152/japplphysiol.00324.2025","DOIUrl":"10.1152/japplphysiol.00324.2025","url":null,"abstract":"<p><p>Whether the noninvasive plateau phase of the skin blood flow response to local heating correlates with more invasive, direct quantification of the NO component is unresolved. To reliably quantify how well these two variables relate to each other, a large sample size is required. We therefore retrospectively analyzed data from 194 young adults at a control microdialysis site that was perfused with lactated Ringer's solution. Skin blood flow was measured using laser-Doppler flowmetry, and the skin was heated from 33 to 39°C. Perfusion of the nonspecific NO synthase inhibitor, N(G)-Nitro-L-arginine methyl ester (L-NAME) (20 mM), was used to quantify the NO component. Data were analyzed using multivariable linear regression. The local heating plateau and NO component were calculated and expressed in multiple ways based on a recently published analysis (Wolf ST, et al<i>. J Appl Physiol (1985)</i> 137: 1418-1424, 2024). There was a positive linear association between the local heating plateau, expressed as the total local heating response, and the NO component, expressed as Δ%CVC<sub>max</sub>. The relation between the plateau and other indices of the NO component appears to largely depend on how the NO component is calculated and expressed. We also found that the relation between the total local heating response and Δ%CVC<sub>max</sub> was not influenced by racial identity or biological sex. Our retrospective analysis of a large cohort of participants suggests that the noninvasive local heating plateau may serve as a reliable surrogate for the more invasive quantification of the NO component when the ability to use more invasive methods is not feasible.<b>NEW & NOTEWORTHY</b> The ability to assess NO-dependent dilation using noninvasive methods has important clinical implications. Here we show that there is a strong relationship between the skin blood flow plateau response to local heating (noninvasive) and directly quantified NO-dependent dilation (invasive).</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"454-464"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637110","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}
Camilla Tvede Schytz, Joachim Nielsen, Niels Ørtenblad, Anne-Kristine Meinild Lundby, Robert Acton Jacobs, Carsten Lundby
{"title":"Effect of high-altitude exposure on skeletal muscle mitochondrial subcellular distribution, ultrastructure, and respiration in sea-level residents.","authors":"Camilla Tvede Schytz, Joachim Nielsen, Niels Ørtenblad, Anne-Kristine Meinild Lundby, Robert Acton Jacobs, Carsten Lundby","doi":"10.1152/japplphysiol.00042.2025","DOIUrl":"10.1152/japplphysiol.00042.2025","url":null,"abstract":"<p><p>The skeletal muscle mitochondrial network, composed of interconnected subsarcolemmal and intermyofibrillar mitochondria, is essential for oxygen-dependent energy transduction. Since high altitude is characterized by tissue hypoxia, this network may adapt by increasing its respiratory efficiency, but little is known about potential adaptations of the mitochondrial network in such an environment. We investigated the effects of high-altitude exposure on mitochondrial subcellular distribution, ultrastructure, respiratory control, and intrinsic respiratory capacity. Nine healthy and recreationally active sea-level residents (8 males and 1 female) resided at an altitude of 3,454 m, with biopsies collected from the vastus lateralis muscle before and after 7 and 28 days at high altitude. Mitochondrial volume per skeletal muscle fiber volume (total fiber mitochondrial volume density) increased after high-altitude exposure, driven by an increase in the intermyofibrillar mitochondrial volume density (<i>n</i> = 9). This was, however, accompanied by a decreased cristae surface area per skeletal muscle fiber volume (total fiber cristae density) because of a decline in the cristae surface area per mitochondrial volume (mitochondrial cristae density) (<i>n</i> = 7). Despite a reduced total fiber cristae density, mass-specific respiration increased slightly (<i>n</i> = 9) and was considerably elevated when normalized to total fiber cristae density (<i>n</i> = 7), suggesting intrinsic adjustments. Correcting cristae-specific respiration for an associated cristae-specific leak respiration showed a higher net oxidative phosphorylation capacity, meaning an augmented respiratory capacity potentially available for phosphorylation per total fiber cristae density after 7 and 28 days at high altitude (<i>n</i> = 7). In conclusion, these findings suggest that high-altitude exposure alters mitochondrial subcellular distribution and ultrastructure and induces intrinsic mitochondrial respiratory adjustments.<b>NEW & NOTEWORTHY</b> Skeletal muscle mitochondrial networks may adapt to high altitude by improving respiratory efficiency. We show that despite an increased mitochondrial volume density following a 28-day sojourn at 3,454 m, the surface area of the infoldings of the inner mitochondrial membrane (cristae) decreased within the muscle fiber due to a decline in the mitochondrial cristae density. However, respiration per cristae surface area increased following 7 and 28 days, suggesting intrinsic adjustments.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"482-495"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560231","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}