{"title":"Competing influences of arterial pressure and carbon dioxide on the dynamic cerebrovascular response to step transitions in exercise intensity.","authors":"Eric T Hedge, Richard L Hughson","doi":"10.1152/japplphysiol.00643.2024","DOIUrl":"10.1152/japplphysiol.00643.2024","url":null,"abstract":"<p><p>Recent investigations of middle cerebral artery blood velocity (MCAv) kinetics at the onset of exercise have not accounted for potential dynamic changes in arterial partial pressure of carbon dioxide ([Formula: see text]) during the transient phase of exercise transitions when modeling MCAv kinetics, despite [Formula: see text] having known effects on cerebrovascular tone. The purpose of our study was to determine the independent effects of mean arterial pressure (MAP) and estimated [Formula: see text] ([Formula: see text]) on mean MCAv during repeated moderate-intensity exercise transitions. We hypothesized that cerebral autoregulation would minimize the effect of sustained exercise-induced changes in MAP on mean MCAv and that dynamic changes in [Formula: see text] would contribute to changes in mean MCAv. Eighteen young healthy adults (7 women, age: 28 ± 5 yr) performed three exercise transitions from 25 W to 90% of the ventilatory threshold in sequence with 5-min stages. Mean MCAv increased (<i>P</i> < 0.001) from 25 W (60.5 ± 14.0 cm·s<sup>-1</sup>) to 90% of the ventilatory threshold (68.8 ± 15.1 cm·s<sup>-1</sup>). MAP at the level of the middle cerebral artery (MAP<sub>MCA)</sub> (Δ = 14 ± 8 mmHg, <i>P</i> < 0.001) and [Formula: see text] (Δ = 2.7 ± 1.8 mmHg, <i>P</i> < 0.001) also increased with exercise intensity. Autoregressive moving average (ARMA) analysis isolated the independent effects of dynamic changes in MAP<sub>MCA</sub> and [Formula: see text] on MCAv, with low prediction error (mean absolute error = 1.12 ± 0.25 cm·s<sup>-1</sup>). Calculated steady states of the ARMA step responses were 0.13 ± 0.15 cm·s<sup>-1</sup>·mmHg<sup>-1</sup> for Δmean MCAv/ΔMAP<sub>MCA</sub> and 1.95 ± 0.83 cm·s<sup>-1</sup>·mmHg<sup>-1</sup> for Δmean MCAv/Δ[Formula: see text]. These data demonstrate that the combination of dynamic changes in MAP and [Formula: see text] largely explains the MCAv response during transitions in exercise intensity.<b>NEW & NOTEWORTHY</b> Time-series analysis of moderate-intensity exercise transitions suggested that cerebral autoregulation buffered the effect of sustained changes in mean arterial pressure on middle cerebral artery blood velocity (MCAv) and that changes in estimated arterial partial pressure of carbon dioxide ([Formula: see text]) contributed to the dynamic changes in MCAv during exercise transitions. Therefore, changes in [Formula: see text] at the onset of exercise are central to modeling dynamic MCAv responses and understanding the benefits of exercise on cerebral blood flow.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"816-824"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492190","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":"MEGA: a computational framework to simulate the acute respiratory distress syndrome.","authors":"Claire Bruna-Rosso, Salah Boussen","doi":"10.1152/japplphysiol.00741.2024","DOIUrl":"10.1152/japplphysiol.00741.2024","url":null,"abstract":"<p><p>The acute respiratory distress syndrome (ARDS) is a critical condition that necessitates mechanical ventilation (MV) to ensure sufficient ventilation and oxygenation for patients. Intensivists employ various therapeutic tools such as adjusting positive end-expiratory pressure (PEEP) levels or positioning the patient prone. However, practitioners encounter several challenges when dealing with ARDS: high variability among patients and limited understanding of underlying mechanisms. As a result, decision-making by physicians largely relies on experience. Yet, having the ability to estimate the likelihood of a patient responding to different therapeutic approaches would hold significant clinical value. Moreover, gaining a deeper understanding of the biomechanical and physiological phenomena underlying patient responses could inform the development of new MV strategies for ARDS management. To address these challenges, a coupled physiomechanical computational framework based on patient's computed tomography scan data was conceived and implemented. Simulations were conducted for prone positioning and PEEP-increment scenarios. The model results qualitatively align with both literature data and clinical measurements. However, some results diverge quantitatively from clinical measurements, emphasizing the necessity for thorough model calibration. Nonetheless, this serves as a proof of concept that the developed framework could be valuable in supporting intensivists' decision-making processes.<b>NEW & NOTEWORTHY</b> An original computational framework has been developed to simulate respiratory biomechanics and physiology of patients with ARDS. Using patient's CT scans, this spatially resolved model enables the calculation of global parameters (e.g., tidal volumes), but also the detailed distribution of ventilation within the lung, a capability not achievable with conventional single-compartment models commonly used in clinical practice. Furthermore, the framework allows to simulate recruitment maneuvers, including those regularly performed in ICU, such as prone positioning.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"825-835"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414396","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}
Julian Brito, Gregory J Grosicki, Austin T Robinson, Jared W Coburn, Pablo B Costa, Kristen E Holmes, Gabrielle Lyon, Zoe Hakonsson, Federica Conti, Andrew J Galpin
{"title":"Hormonal birth control is associated with altered gut microbiota β-diversity in physically active females across the menstrual cycle: a pilot trial.","authors":"Julian Brito, Gregory J Grosicki, Austin T Robinson, Jared W Coburn, Pablo B Costa, Kristen E Holmes, Gabrielle Lyon, Zoe Hakonsson, Federica Conti, Andrew J Galpin","doi":"10.1152/japplphysiol.00008.2025","DOIUrl":"10.1152/japplphysiol.00008.2025","url":null,"abstract":"<p><p>Understanding changes to gut microbiota composition in response to hormonal birth control (HBC) may provide insight into the microbial mechanisms underlying the metabolic effects of HBC, for example, altered short-chain fatty acid (SCFA) production. Athletes' unique physiological demands may interact with these microbial mechanisms in distinct ways; however, there is limited research on HBC and gut microbiota diversity and composition across different menstrual cycle phases in physically active females. A pilot cohort of physically active females using HBC (oral contraceptives, hormone-based intrauterine devices, or arm implants) and a control group not using HBC (<i>n</i> = 12 per group; 22 ± 2 yr, 24 ± 4 kg/m<sup>2</sup> vs. 22 ± 4 yr, 23 ± 4 kg/m<sup>2</sup>; <i>P</i>s ≥ 0.496) provided fecal samples alongside self-reported menstrual phase and circulating sex hormones. α-diversity (microbial richness and evenness) was assessed using the Shannon index whereas β-diversity (microbial composition differences) was analyzed using PERMANOVA based on Bray-Curtis dissimilarity. Circulating estrogen and luteinizing hormone increased from early (<i>days 1</i>-<i>5</i>) to mid-cycle (<i>days 12</i>-<i>17</i>) in both groups (time effect <i>P</i>s ≤ 0.01), with greater changes in Control (<i>P</i>s ≤ 0.046) than HBC (<i>P</i>s ≥ 0.231). Although no menstrual phase effect was observed on either diversity measure (<i>P</i>s ≥ 0.473), β-diversity differed between Control and HBC groups (<i>P</i> = 0.015), reflecting distinct gut microbiota profiles irrespective of menstrual phase. Seven taxa linked to SCFA production were less abundant in the HBC group (unadjusted <i>P</i>s ≤ 0.046), though significance was lost after adjusting for multiple comparisons. These findings suggest that in physically active females, hormonal contraception influences gut microbial composition, which may have downstream effects on metabolism and performance.<b>NEW & NOTEWORTHY</b> This study is the first to investigate interactions between hormonal contraception and the gut microbiota in a cohort of physically active young females across the menstrual cycle. Our findings suggest that hormonal contraception may influence gut microbiota composition, potentially through a reduced relative abundance of short-chain fatty acid-producing taxa. Experimental studies are needed to confirm these associations and explore their potential implications for metabolism, health, and performance.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"739-745"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416791","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}
Stephen P Wright, Tony G Dawkins, Megan I Harper, Mike Stembridge, Hannah Martin-Spencer, Rob Shave, Neil D Eves
{"title":"Intrathoracic pressure deviations attenuate left ventricular filling and stroke volume without pronounced myocardial mechanical alterations in healthy adults.","authors":"Stephen P Wright, Tony G Dawkins, Megan I Harper, Mike Stembridge, Hannah Martin-Spencer, Rob Shave, Neil D Eves","doi":"10.1152/japplphysiol.00724.2024","DOIUrl":"10.1152/japplphysiol.00724.2024","url":null,"abstract":"<p><p>Intrathoracic pressure modulates cardiac loading conditions, which then influence left ventricular (LV) chamber function, and may occur with underlying myocardial mechanical alterations. We investigated the independent effects of inspiratory negative and expiratory positive intrathoracic pressure on septal geometry, LV chamber function, and rotation, twist, and strain indices. After baseline, 20 healthy adults (11M/9F, 23 ± 4 yr) performed resistive breathing to manipulate inspiratory (-30, -20, -10 cmH<sub>2</sub>O) or expiratory (+10, +20 cmH<sub>2</sub>O) intrathoracic pressure. Echocardiography was used to acquire LV-focused two-dimensional (2-D) images, and mitral Doppler inflow and annular tissue velocity spectra. Images were analyzed for LV chamber volumes, tissue velocities, transmitral filling velocities, and speckle tracking-derived LV longitudinal, radial, and circumferential strain and strain-rate, basal and apical rotation, and twist. Across negative pressure trials, most profoundly at -30 cmH<sub>2</sub>O, we observed progressive end-diastolic septal flattening (3.9 ± 0.4 vs. 3.2 ± 0.4 cm, <i>P</i> < 0.05) and decreases in LV end-diastolic volume (103 ± 23 vs. 115 ± 25 mL, <i>P</i> < 0.05) and stroke volume, whereas end-systolic volume was unchanged. However, LV apical and basal rotation, twist (13.3° ± 3.6° vs. 13.9° ± 3.7°, <i>P</i> = 0.890), and circumferential, radial, and longitudinal strain indices were largely unchanged. During positive pressure trials, we observed main effects for septal flattening (<i>P</i> = 0.014) confined to inspiration, and modestly reduced LV end-diastolic volume (<i>P</i> < 0.001), end-systolic volume (<i>P</i> = 0.033), and stroke volume. Again, myocardial mechanics parameters changed little. Collectively, our data suggest that both positive and negative intrathoracic pressures can exacerbate direct ventricular interaction through opposing mechanisms that attenuate LV end-diastolic volume and stroke volume, but without specific changes in myocardial mechanics or mitral inflow.<b>NEW & NOTEWORTHY</b> Incrementally more negative or positive intrathoracic pressures, relative to normal dynamic breathing, progressively attenuate left ventricular end-diastolic volume and stroke volume in healthy younger adults. Incrementally more negative or positive intrathoracic pressures were each associated with progressive septal flattening during inspiration, indicating direct ventricular interaction. However, left ventricular transmitral inflow velocities, and myocardial rotation, twist, and circumferential, longitudinal, and radial strain parameters changed little.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"681-692"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382563","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}
Lauren M Colenso-Semple, James McKendry, Changhyun Lim, Philip J Atherton, Daniel J Wilkinson, Kenneth Smith, Stuart M Phillips
{"title":"Oral contraceptive pill phase does not influence muscle protein synthesis or myofibrillar proteolysis at rest or in response to resistance exercise.","authors":"Lauren M Colenso-Semple, James McKendry, Changhyun Lim, Philip J Atherton, Daniel J Wilkinson, Kenneth Smith, Stuart M Phillips","doi":"10.1152/japplphysiol.00035.2025","DOIUrl":"10.1152/japplphysiol.00035.2025","url":null,"abstract":"<p><p>There is speculation that the use of oral contraceptive pill (OCP) affects skeletal muscle biology and protein turnover in response to resistance exercise; however, research in this area is scarce. We aimed to assess, using stable isotope tracers and skeletal muscle biopsies, how second-generation OCP phase affected muscle protein synthesis and whole body proteolysis. Participants (<i>n</i> = 12) completed two 6-day study phases in a randomized order: an active pill phase (active; <i>week 2</i> of a monthly active OCP cycle) and an inactive pill phase (inactive; final week of a monthly OCP cycle). They performed unilateral resistance exercise in each study phase, exercising the contralateral leg in the opposite phase in a randomized, counterbalanced order. The active phase myofibrillar protein synthesis (MPS) rates were 1.44 ± 0.14%·day<sup>-1</sup> in the control leg and 1.64 ± 0.15%·day<sup>-1</sup> in the exercise leg (<i>P</i> < 0.001). The inactive phase MPS rates were 1.49 ± 0.12%·day<sup>-1</sup> in the control leg and 1.71 ± 0.16%·day<sup>-1</sup> in the exercise leg (<i>P</i> < 0.001), with no interaction between phases (<i>P</i> = 0.63). There was no significant effect of OCP phase on whole body myofibrillar proteolytic rate (active phase <i>k</i> = 0.018 ± 0.01; inactive phase <i>k</i> = 0.018 ± 0.006; <i>P</i> = 0.55). Skeletal muscle remains equally as responsive, in terms of stimulation of MPS, during active and inactive OCP phases; hence, our data do not support a proanabolic or catabolic, based on myofibrillar proteolysis, effect of OCP phase on skeletal muscle in females.<b>NEW & NOTEWORTHY</b> We discovered that women taking a second-generation oral contraceptive pill (OCP) showed no difference in integrated daily muscle protein synthesis or whole body myofibrillar proteolysis in the active or placebo pill phases of the pill cycle. Our data show that OCP phase neither influences skeletal muscle protein turnover in females and nor supports a marked procatabolic or anabolic effect.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"810-815"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515700","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}
Jacob P Hartmann, Stine Buus Nymand, Helene Louise Hartmeyer, Camilla Koch Ryrsø, Amalie B Andersen, Milan Mohammad, Iben Elmerdahl Rasmussen, Rie Skovly Thomsen, Cody Garett Durrer, Ronan M G Berg, Ulrik Winning Iepsen
{"title":"Effect of 12 weeks of interval training on skeletal muscle blood flow during single-leg knee extensor exercise in COPD: a nonrandomized controlled trial.","authors":"Jacob P Hartmann, Stine Buus Nymand, Helene Louise Hartmeyer, Camilla Koch Ryrsø, Amalie B Andersen, Milan Mohammad, Iben Elmerdahl Rasmussen, Rie Skovly Thomsen, Cody Garett Durrer, Ronan M G Berg, Ulrik Winning Iepsen","doi":"10.1152/japplphysiol.00798.2024","DOIUrl":"10.1152/japplphysiol.00798.2024","url":null,"abstract":"<p><p>High-intensity interval training (HIIT) has shown to improve exercise capacity, symptom burden, and quality of life in patients with chronic obstructive pulmonary disease (COPD), but it remains to be investigated if HIIT can counteract limb muscle dysfunction. Therefore, we examined the impact of a 12-wk supervised HIIT protocol on muscle oxygen conductance. Eight patients with mild-to-moderate COPD and eight age-, sex-, and BMI-matched controls underwent a 12-wk HIIT intervention. Leg blood flow ([Formula: see text]) and arterio-venous blood samples were collected at rest and during active single-leg knee-extensor exercise (KEE) at unloaded (0 W) and 20% of peak workload (W<sub>Lpeak</sub>) to estimate leg muscle oxygen conductance pre- and post-HIIT. In pre-HIIT, [Formula: see text] was similar between groups during unloaded KEE (<i>P</i> = 0.108) but lower at 20% W<sub>Lpeak</sub> in the COPD group, compared with the control group. [Formula: see text] responses were higher during unloaded KEE (28%, <i>P</i> = 0.012) and 20% W<sub>Lpeak</sub> (40%, <i>P</i> < 0.001) post-HIIT in the COPD group, whereas no change occurred in the control group. Flow-adjusted skeletal muscle O<sub>2</sub> conductance was higher in the COPD pre-HIIT group but only increased in the control group. Thus, there was no difference in diffusive or convective capacity between groups post-HIIT at submaximal KEE. COPD assessment score decreased by 2.8 [1;4] (<i>P</i> = 0.003) in the COPD group and V̇o<sub>2peak</sub> increased in both groups (COPD 192 mL O<sub>2</sub>/min, <i>P</i> = 0.032, control 257 mL O<sub>2</sub>/min, <i>P</i> = 0.004) with no time/group interaction. A 12-wk HIIT intervention may improve peripheral exercise capacity in COPD by increasing the vasodilatory function in working muscle while concurrently improving whole-body exercise capacity and symptom burden.<b>NEW & NOTEWORTHY</b> Individuals with COPD exhibit lower blood flow to the exercising leg muscles, which may be considered part of the limb muscle dysfunction associated with the disease. A 12-wk high-intensity interval training (HIIT) program increased leg blood flow in patients with COPD during single-leg knee extensor exercise achieved by improving the vasodilatory response. HIIT also improved maximal oxygen uptake and exercise capacity while reducing symptom burden.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"836-847"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492192","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}
Kylie Jones, Savanna Smith, Jonna Smith, Angie Castillo, Allison Burkes, Ahfiya Howard, Madison M Garvin, Jessica L Bolton, Luis Colon-Perez, Mark W Cunningham
{"title":"Postpartum dams exposed to a low-resource environment display neuroinflammation, elevated corticosterone, and anhedonia-like behavior.","authors":"Kylie Jones, Savanna Smith, Jonna Smith, Angie Castillo, Allison Burkes, Ahfiya Howard, Madison M Garvin, Jessica L Bolton, Luis Colon-Perez, Mark W Cunningham","doi":"10.1152/japplphysiol.00871.2024","DOIUrl":"10.1152/japplphysiol.00871.2024","url":null,"abstract":"<p><p>Women living in an impoverished environment after birth have an increased risk of developing postpartum depression (PP-Dep) and hypertension (PP-HTN). The mechanisms underlying these heightened risks are unknown and understudied. To examine the relation between reduced environmental resources, PP-Dep, and PP-HTN, postpartum rodent dams were exposed to the low-resource limited bedding and nesting (LBN) chronic stress model during weaning. Postpartum dams were divided into control (CTL) and experimental (LBN) groups, in which the experimental group experienced LBN. At 6 wks postpartum, blood pressure, sucrose preference tests (a proxy for anhedonia and depression), corticosterone, and markers of neuroinflammation were measured. We hypothesized that postpartum dams exposed to LBN will have increased corticosterone, neuroinflammation, depression-like behaviors, and HTN. Results show that postpartum dams exposed to an impoverished environment exhibit decreased sucrose preference, increased circulating corticosterone, and elevated neuroinflammation (∼150% increased TNF-α and astrocyte activation in the cerebrum). No changes in blood pressure were observed. However, there was a strong correlation between postpartum blood pressure and corticosterone and blood pressure and TNF-α levels. Importantly, this study provides insights into the pathology and development of PP-HTN and PP-Dep in the postpartum period, which will enable the discovery of novel therapeutic approaches.<b>NEW & NOTEWORTHY</b> Postpartum dams exposed to a low-resource environment experience anhedonia, elevated corticosterone, and neuroinflammation. Increases in corticosterone and neuroinflammation may contribute to the development of postpartum depression (PP-Dep) and postpartum hypertension (PP-HTN). Healthcare providers should consider asking questions about the social economic status and accessibility of resources for women after pregnancy. This study advocates for extended postpartum care beyond traditional care and better implementation of assessments for PP-Dep and PP-HTN.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"666-680"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065884","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}
Yanna Liu, Li Wang, Sirui Jiao, Xiaohan Yang, Gang Liu, Kai Fan, Henan Zhao, Jianmei Ma
{"title":"Cardiac dilation, energy stress, and ventricular remodeling: insights from prolonged voluntary exercise in male mice with TAC-induced HFpEF.","authors":"Yanna Liu, Li Wang, Sirui Jiao, Xiaohan Yang, Gang Liu, Kai Fan, Henan Zhao, Jianmei Ma","doi":"10.1152/japplphysiol.00275.2024","DOIUrl":"10.1152/japplphysiol.00275.2024","url":null,"abstract":"<p><p>Exercise in heart failure with preserved ejection fraction (HFpEF) remains a hot topic, although current treatment strategies have not been shown to improve the long-term prognosis of HFpEF. Previous studies have mostly focused on the roles of endurance training; the mechanisms underlying long-term voluntary exercise have not been elucidated. The purpose of the present analysis was to evaluate alterations in cardiac function in HFpEF mice (HFpEF-Sed) after 6 wk of voluntary running (HFpEF-Ex), investigate mechanisms, and compare the effects with fluoxetine (HFpEF-FLX). We found that voluntary exercise, instead of fluoxetine intervention, significantly improved left ventricular end-diastolic internal diameter (LVIDd) and the rate of change in anterior wall thickness (AWT) in HFpEF mice. The exercise capacity of HFpEF-Sed mice was significantly reduced, but prolonged voluntary running significantly reversed the expression of myocardial brain natriuretic peptide (BNP), TNF-α, and IL-6, α-myosin heavy chain (α-MHC), and β-MHC in HFpEF-Sed mice, along with myocardial fiber disorders accompanied by massive inflammatory cell infiltrates. Importantly, myocardial complex III and complex V, Mfn2, Drp1, p62, and LC3 II/I expression in HFpEF-Sed mice were all significantly different from those of normal mice, whereas voluntary exercise significantly reversed these expressions. These findings strongly suggest that long-term voluntary exercise is effective in avoiding acute and chronic energy stress in HFpEF-Sed mice, which is consistent with the mechanism of current first-line treatment for HFpEF. This notion was further supported by electron microscopy results, which showed no pathological features in cardiomyocyte mitochondrial morphology after prolonged voluntary exercise. In addition, fluoxetine was found to inhibit depressive-like behavior in HFpEF mice.<b>NEW & NOTEWORTHY</b> As a self-initiating, self-sustaining, and low-cost treatment for patients with heart failure, how voluntary exercise plays its roles in interfering with the pathophysiologic pathways associated with HFpEF is still largely unknown. The results of this study indicate that long-term voluntary exercise can effectively antagonize acute and chronic dual-energy stress and avoid diastolic function limitation caused by pathological ventricular remodeling.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"746-760"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052640","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}
D Karmali, S Afanador-Castiblanco, T Ötvös, G Aguilar, S Hossen, N Eikelis, K Nilsen, N M Punjabi, T Siddharthan, J P Kirkness
{"title":"Regional lung volume changes with noninvasive positive pressure ventilation in healthy adults.","authors":"D Karmali, S Afanador-Castiblanco, T Ötvös, G Aguilar, S Hossen, N Eikelis, K Nilsen, N M Punjabi, T Siddharthan, J P Kirkness","doi":"10.1152/japplphysiol.00676.2024","DOIUrl":"10.1152/japplphysiol.00676.2024","url":null,"abstract":"<p><p>Noninvasive assessments of lung volume distribution often require inhaled contrast and are limited by low regional resolution. We aimed to examine a noncontrast imaging method of spatial lung volume displacement, adapted to assess changes with noninvasive positive pressure ventilation (NIPPV). This study evaluated regional lung volume displacement in nine healthy volunteers (6 males and 3 females; ages 29-55 yr; body mass index 20.2-31.3 kg/m<sup>2</sup>) using X-ray velocimetry (XV). Participants were assessed during tidal breathing and, also with 15 cmH<sub>2</sub>O inspiratory and 5 cmH<sub>2</sub>O expiratory pressures in a supine position. Regional specific ventilation (SV) was measured during tidal breathing and NIPPV. Mean specific ventilation (MSV, mL/mL), low-volume region (LVR; % < 0.1 mL/mL), and high-volume region (HVR; % > 0.3 mL/mL) were calculated as output variables. Images were segmented into lobar as well as central and peripheral zones. Two-way ANOVA and paired <i>t</i> tests were used to determine regional differences within individuals and the effect of NIPPV. NIPPV increased MSV in both peripheral (<i>P</i> = 0.01) and central (<i>P</i> = 0.02) lung regions compared with tidal breathing. High-volume regions increased in both peripheral (<i>P</i> = 0.04) and central regions (<i>P</i> = 0.04) during NIPPV. This study demonstrates that noncontrast imaging techniques can assess regional lung ventilation and redistribution of lung volumes on NIPPV. Heterogeneous responses to NIPPV may be associated with a distinct distribution of ventilation, and further work is needed to ascertain differential responses to NIPPV due to lung pathology among those with respiratory disease.<b>NEW & NOTEWORTHY</b> Noninvasive positive pressure ventilation (NIPPV) is a commonly utilized intervention for acute and chronic respiratory failure. In this study, we use functional lung imaging to describe changes in regional lung ventilation and redistribution of lung volume with NIPPV. These results offer insight into the regional effects of NIPPV on volume expansion with the use of functional imaging.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"731-738"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143408103","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}
Alexander B Sklivas, Zachary R Hettinger, Sarah Rose, Alessandra Mantuano, Amy L Confides, Sandra Rigsby, Frederick F Peelor, Benjamin F Miller, Timothy A Butterfield, Esther E Dupont-Versteegden
{"title":"Responses of skeletal muscle to mechanical stimuli in female rats following and during muscle disuse atrophy.","authors":"Alexander B Sklivas, Zachary R Hettinger, Sarah Rose, Alessandra Mantuano, Amy L Confides, Sandra Rigsby, Frederick F Peelor, Benjamin F Miller, Timothy A Butterfield, Esther E Dupont-Versteegden","doi":"10.1152/japplphysiol.00802.2024","DOIUrl":"10.1152/japplphysiol.00802.2024","url":null,"abstract":"<p><p>The purpose of this study was to investigate the ability of mechanotherapy to enhance recovery or prevent loss of muscle size with disuse in female rats. Female F344/BN rats were assigned to weight bearing (WB), hindlimb suspended (HS) for 14 days with reambulation for 7 days without mechanotherapy or reambulation (RA) with mechanotherapy (RAM) (<i>study 1</i>), or to WB, HS for 7 days, with HS mechanotherapy (HSM) or without mechanotherapy (<i>study 2</i>) to gastrocnemius muscle. Muscle fiber cross-sectional area (CSA) and fiber type, collagen, satellite cell number, and protein synthesis (<i>k</i><sub>syn</sub>) and degradation (<i>k</i><sub>deg</sub>) were assessed. <i>Study 1</i>: muscle weight, but not CSA, was higher in RAM compared with HS, but CSA was higher in RA compared with HS. Myofibrillar <i>k</i><sub>syn</sub> was higher in RA and RAM compared to WB and HS but not different between RA and RAM. Myofibrillar <i>k</i><sub>deg</sub> was lower with mechanotherapy compared to HS. <i>Study 2</i>: muscle weight, CSA, and myofibrillar <i>k</i><sub>syn</sub> and <i>k</i><sub>deg</sub> were not different with mechanotherapy. Collagen content was lower with mechanotherapy but collagen <i>k</i><sub>syn</sub> was not. Mechanotherapy was not associated with changes in fiber type, satellite cell, or myonuclear number in either study. Compared to males, female rats had less muscle loss with HS, which was associated with less loss of myofibrillar <i>k</i><sub>syn</sub>. Recovery from atrophy was associated with higher <i>k</i><sub>syn</sub> in female and lower <i>k</i><sub>deg</sub> in male rats. Female rat muscles do not exhibit a growth response to mechanotherapy with disuse or reambulation. Furthermore, male and female rats show distinct responses to different mechanical stimuli.<b>NEW & NOTEWORTHY</b> This study investigates the response of female rats to mechanical stimulation in both active and passive forms following and during muscle disuse atrophy. New findings indicate that female rats respond to active loading with enhanced muscle regrowth and protein synthesis, whereas passive loading using mechanotherapy did not affect atrophy or recovery of female muscles. Comparison with published data indicates that there are distinct differences in male and female rats in their response to mechanical stimuli.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"652-665"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065891","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}