BACKGROUND:Patients with COPD and chronic respiratory failure (CRF) receiving long-term oxygen therapy experience exaggerated quadriceps neuromuscular fatigue (NMF). In this context, the effect of oxygen therapy on NMF remains unclear. RESEARCH QUESTION:What is the impact of different Fio2 levels on neuromuscular fatigue during intermittent isometric quadriceps exercise in a population with COPD and CRF? STUDY DESIGN AND METHODS:Three intermittent isometric quadriceps tests, all at 80% of the time to exhaustion (TTE) at 30% of maximal voluntary contraction (MVC), were performed randomly in each patient with 3 different Fio2 measurements: 21%, 30%, and 60%. TTE was evaluated previously by breathing Fio2 at 21%. NMF was assessed through changes in MVC, twitch force quadriceps potentiated (Qtwpot), and voluntary activation (VA) after exercise (at peak, and at 30 seconds and 10 minutes after). Electromyography results were evaluated continuously. RESULTS:We enrolled 20 patients (80.9% male; mean [SD] age, 71.80 [5.81] years; mean [SD] FEV1 to FVC ratio, 39.56 [9.32]; mean [SD] residual volume, 206.49% [53.14%]). Mean (SD) MVC changes were -27.60% (9.50%), -24.35% (7.80%), and -22.00% (7.13%) for the 21%, 30%, and 60% tests, respectively (P = .0341), with differences between the 21% and 30% Fio2 measurements (P = .032) and 21% and 60% tests (P = .032). Qtwpot showed mean (SD) changes of -31.10% (14.30%), -31.25% (16.70%), and -26.70% (16.10%) for the 21%, 30%, and 60% tests, respectively (P = .019), with differences between the 21% and 60% tests (P = .027) and the 30% and 60% tests (P = .014). VA decreased similarly across conditions (P = .211). INTERPRETATION:Our results show that acute oxygen administration reduces quadriceps NMF in patients with COPD and CRF. These results highlight the role of oxygen availability in modulating NMF in this population. Future studies should investigate this effect during exercise training, as well as long-term consequences. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT05533957; URL: www. CLINICALTRIALS:gov.

Background:Acute exacerbations of COPD (AECOPDs) may cause exercise-induced desaturation (EID), affecting recovery and rehabilitation outcomes. The prevalence and clinical implications of EID during early postexacerbation pulmonary rehabilitation are unclear. This study aimed to determine the prevalence of EID in COPD patients recovering from AECOPDs, with and without long-term oxygen therapy (LTOT) at rest, and to compare clinical, functional, and physiological characteristics. Methods:This retrospective, multicenter study included 262 COPD patients admitted for inpatient pulmonary rehabilitation after AECOPDs. Participants were stratified by resting oxygen therapy status. EID was defined as a ≥4% fall in peripheral oxygen saturation from baseline with nadir <90% during the 6-minute walking test. Clinical, functional, and physiological parameters were compared across subgroups. Results:Overall, 132 patients (50.4%) exhibited EID. Prevalence was higher in patients on oxygen at rest (61.5%) than in those breathing room air (33.9%, p <0.0001). Patients on oxygen therapy had greater lung function impairment, reduced exercise capacity, and higher dyspnea-related disability. EID was associated with greater heart rate response in patients on supplemental oxygen but not consistently with perceived dyspnea or fatigue, highlighting the importance of objective oximetry during exercise testing. Regardless of EID, individuals on oxygen walked shorter distances than those on room air. Conclusions:EID is common in COPD patients recovering from AECOPD, especially those receiving LTOT, and is linked to more severe functional impairment. Systematic EID assessment using objective oximetry during early pulmonary rehabilitation may support individualized oxygen titration and exercise prescriptions. Prospective studies are needed to clarify its prognostic implications.

The number of people with dementia is around 50 million worldwide and this number is expected to grow in the coming decades. To date, scientific evidence suggests that physical activity is an encouraging aid in slowing down the progression of dementia and has positive effects on many aspects: metabolic, independence in activities of daily living (ADLs), cognitive and muscle strength. However, few studies analyze the feasibility and the effects of high-intensity exercise programs in people with dementia. The aim is to synthesize evidence on the feasibility of high-intensity exercise training (HIET) in people with dementia and/or Mild Cognitive Impairment (MCI) and to evaluate its effects on cognition, physical performance, ADLs, neuropsychiatric symptoms and quality of life. Clinical trials and RCTs published up to March 2025 were selected through searches in PubMed, Scopus and Google Scholar, using MeSH terms related to dementia and high-intensity physical exercise. Studies involving people with dementia and/or MCI undergoing high-intensity aerobic and/or strength training were included. Methodological quality was assessed using the PEDro scale, and risk of bias was evaluated with the Cochrane RoB 2 tool. 21 studies met inclusion criteria, including participants with dementia and/or MCI. Feasibility was generally supported and the dropout rate was 13

Assessing regional vascular function is crucial for understanding systemic cardiovascular health. This study primarily investigated whether flow-mediated dilation (FMD) and passive limb movement (PLM) yield congruent, interchangeable patterns across the upper limbs (ULs) and lower limbs (LLs). Secondarily, we evaluated sex-specific influences on these regional vascular relationships. Twenty healthy individuals (10 males and 10 females) underwent brachial and popliteal FMD, alongside axillary and femoral PLM, in a counterbalanced single session. Baseline diameters, FMD%, allometrically scaled FMD, and blood flow (BF) PLM parameters [peakBF, ΔpeakBF, area under the curve (AUC)] were analyzed. Regarding our primary aim, FMD% was significantly higher in UL than LL (7.7 ± 2.9% vs. 4.9 ± 1.8%; P = 0.002) and was not correlated between limbs (r = 0.11, P = 0.650). However, when analyzed using an allometric mixed model with baseline diameter as a covariate, this limb difference was no longer significant (P = 0.334). PLM ΔpeakBF was lower in UL than LL (ΔUL - LL = -68.3%; P < 0.001) but showed significant interlimb correlations (r = 0.50, P = 0.024). No limb × sex interaction was found for FMD% (P = 0.889) or allometric FMD% (P = 0.815). However, a significant limb × sex interaction emerged for PLM AUC (P < 0.001), driven by a higher absolute AUC in the LL for males (P < 0.001) and a higher volume-normalized AUC in the UL for females (P = 0.003). In conclusion, brachial and popliteal FMD are not interchangeable, providing complementary, region-specific information heavily influenced by vessel size, and FMD% is not affected by sex. PLMUL and PLMLL provide partially convergent but not equivalent information, warranting caution when comparing limbs, particularly when sex is a variable of interest.NEW & NOTEWORTHY This study directly compares flow-mediated dilation and passive limb movement across upper and lower limbs, providing novel insight into limb-specific vascular function. Flow-mediated dilation and passive limb movement are not interchangeable between limbs, impacting future experimental and clinical evaluation. Vascular function differs between sexes for passive limb movement, highlighting the need to consider sex-specific effects in study design.

Introduction: Intradialytic exercise (IE) is an effective non-pharmacological intervention for patients undergoing hemodialysis (HD). During exercise training, increased blood flow (BF) within the exercising muscle is driven by elevated endothelial shear stress (SS) that is proportional, at least in part, to blood viscosity (BV). Although ultrafiltration during HD session reduces plasma volume, thereby increasing BV, it remains unclear whether this change in BV influences peripheral circulation during IE. Therefore, the aim of this cross-sectional study was to examine the effects of IE on BV and peripheral/central hemodynamics. Methods: Patients receiving maintenance 4-hour haemodialysis sessions for at least 3 months were included. BF and vascular conductance (VC) at the brachial artery were measured using Doppler ultrasound. Stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP) and heart rate (HR) were continuously monitored via finger plethysmography. BV was determined from hematocrit. All measurements were obtained at baseline (T0) and at 4 hours (T1) during a 4-hour dialysis session and a 4-hour interdialytic period (Sham). At each time point, patients performed IE through intermittent handgrip exercise at workloads of 3, 6, and 9 kg. Demographic and laboratory data were also collected. Results: 12 out of 27 patients were enrolled. BF increased progressively with workload in sham and HD periods. Compared to Sham period, BF in HD was statically significant higher at 6kg (199.1±48.2 vs. 156.1±39.2 ml/min; p< 0.05) and 9kg (289.1±54.9 vs. 223.8±49.5 ml/min; p< 0.05) but not at 3kg (139.1±32.1 vs. 135.6±26.3 ml/min). Similarly, VC increased with workload in HD (3% at 3kg; 34% at 6kg, p< 0.05; 43% at 9kg, p< 0.05). Conversely, SV, CO and MAP, indices of central hemodynamic, were significantly lower in HD (-22% at 3kg, -15% at 6kg, -9% at 9kg, p< 0.05) than Sham period. Conversely, HR increased in HD at T1 (+16%), suggesting a compensatory chronotropic response to reduced plasma volume. BV significantly higher in HD period at T1 compared to Sham (4.2±0.5 vs. 3.3±0.6 cP; p < 0.05). Conclusion: IE increased BV and peripheral vasodilation, resulting in greater BF and VC. This augmented peripheral response occurred despite reductions in central hemodynamics, suggesting that viscosity-mediated SS plays a key role in regulating peripheral hemodynamics during IE. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Chronic kidney disease (CKD) and peripheral artery disease (PAD) are highly prevalent conditions associated with morbidity, mortality, and health-care costs, particularly when they coexist. Despite advances in pharmacological and interventional therapies, patients with both CKD and PAD have rapid functional decline, higher hospitalization rates, and poor cardiovascular outcomes. In populations with either CKD or PAD alone, exercise training has been shown to improve cardiorespiratory fitness, muscle strength, physical function, and quality of life and is strongly recommended in the guidelines. However, evidence for exercise training in patients with overlapping CKD and PAD remains limited with no randomized controlled trials and only a single observational cohort, suggesting potential benefits of home-based walking programs on renal and cardiovascular outcomes. This narrative review examines the potential benefits of exercise training as a nonpharmacological approach to addressing this therapeutic gap. An ongoing randomized controlled trial, EXACT-CKD-PAD, is expected to provide more definitive evidence in this high-risk population, although further studies will be required to define long-term clinical impact and optimal implementation strategies.

Background:Vascular dysfunction has been described as worsening in Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of knowledge regarding severe patients. This retrospective cross-sectional study aimed to investigate it in COPD with Chronic Respiratory Failure (CRF) versus COPD and controls. Methods:A baseline screening was performed, including a health history, a physical examination, and an anthropometric assessment. All subjects underwent an arterial blood gas analysis, spirometry, a 6-min walking test, and a thigh muscle volume assessment. The vascular function was determined via single Passive Leg Movement (sPLM) on the dominant leg. Results:Fifteen patients with moderate COPD (FEV1 53.3% ± 11.4%), 15 patients with severe COPD (CRF; FEV1 30.6% ± 10.3%), and 15 age-matched healthy controls (CTRL) were recruited. Reactive hyperemia following sPLM was decreased in CRF [peak LBF (Leg Blood Flow) 70 ± 38 mL/min)] compared to COPD (peak LBF 162 ± 115 mL/min) and CTRL (peak LBF 268 ± 134 mL/min), p < 0.05. Interestingly, when the vascular function was normalized to the thigh muscle volume, the difference in the hyperaemic response among the CRF, COPD, and CTRL groups was mitigated but not eliminated. Moreover, the peak LBF was associated with the 6-min walking test (r = 0.7027, p < 0,0001), FEV1 (r = 0.5432, p = 0.0001), disease duration (r = 0.5062, p = 0.0004), oxygen saturation (SpO2) (r = 0.4343, p = 0.0029), and prescribed oxygen flow (r = -0.5413, p < 0.0001). Conclusion:These data provide evidence of an intrinsic vascular dysfunction during the progression of COPD, which depends only partially on locomotor muscle volume loss observed in this clinical population.

Poor vascular function and reduced nitric oxide (NO)-bioavailability have been recognized to be involved in aging and Alzheimer's Disease (AD). A non-pharmacological treatment that is gaining clinical interest in the context of vascular function is dietary inorganic nitrate (NO3-) supplementation which increases NO-bioavailability through the NO3- -nitrite (NO2-) - NO pathway. This treatment has been demonstrated to improve vascular function in several clinical populations, but no study has investigated the effects in individuals with AD. Therefore, changes in plasma NO3- and NO2- and vascular responsiveness (hyperemic response to single-passive leg movement (ΔPLM)) were measured in individuals with AD (n = 10, 76 ± 9 years), healthy elderly (OLD, n = 10, 75 ± 6 years), and young individuals (YN, n = 10, 25 ± 4 years) before (T0) and hourly for 4 h (T1, T2, T3, and T4) after ingestion of either NO3--rich beetroot juice (BR) or a placebo (PLA). No changes in NO3- and NO2-, nor ΔPLM were detected in any group following PLA intake. Plasma NO3- and NO2- increased significantly in all three groups at T1 (p < 0.001) and remained elevated for the rest of the trial. The same trend was found in ΔPLM, which significantly increased in all three groups over the time (p < 0.001). However, AD exhibited significantly lower ΔPLM values at any time point compared to YN (p < 0.001) and OLD (p < 0.001). These data suggest that AD-individuals included in this study were able to reduce NO3- to NO2- and to increase NO-mediated vascular responsiveness as non-AD-individuals. Other mechanisms, beyond NO-bioavailability, may be involved in vascular dysfunction in patients with AD. This research suggests that an acute administration of inorganic nitrate is not enough to revert chronically adapted vascular properties and completely restore vascular responsiveness in AD.

AIMS:The aim of this study was to compare the differences in length of stay (LoS) and prior hospitalization due to heart failure (HHF) in patients with HF and frailty versus without frailty. METHODS AND RESULTS:From inception until August 2024, PubMed, Scopus, Web of Science and Cochrane Library were searched. To examine the association related to LoS and HHF in patients with HF, a meta-analysis using a random-effects model was conducted (CRD42024570604). Our main analysis demonstrated a significantly increased LoS in patients with frailty versus those without frailty [n = 10; mean difference (MD): 3.67; 95% CI: 2.26-5.08, I2 = 93%, P < 0.01]. Likewise, patients with frailty had significantly increased odds of HHF [n = 17; odds ratio (OR): 1.76; 95% CI: 1.50-2.07, I2 = 81%, P < 0.01]. Risk of bias assessment of the included studies was overall fair, while Egger's test showed publication bias regarding studies that examined LoS (P = 0.02). CONCLUSIONS:Patients with frailty have longer LoS and more frequent HHF, underscoring the need for early, targeted interventions to manage frailty that may be attributed primarily to ageing and comorbidity-related status.

Reduction in exercise capacity and peak oxygen uptake (V̇O2) are common in acromegaly, but ventilatory alterations during exercise remain unstudied. We evaluated the exercise ventilatory response in terms of efficiency in patients with acromegaly. We prospectively evaluated 10 patients with acromegaly in a phase of disease control. To minimise confounders related to ventilatory response and anthropometric differences, acromegalic patients were matched with 10 control subjects according to age, body mass index, and body surface area. Chronic diseases, any cardio-respiratory condition likely to alter ventilatory response, and evidence of cardiac dysfunction were excluded. Pulmonary function tests and maximal cardiopulmonary exercise testing were performed. Ventilatory response was assessed via minute ventilation (V̇E)/carbon dioxide(CO2) output slope (V̇E/V̇CO2slope) and end-tidal carbon dioxide pressure (PETCO2). Exercise ventilatory inefficiency (EVin) was defined according to reference values for healthy individuals. No alterations in lung function were observed in either group. Compared with controls, patients with acromegaly showed lower power output and V̇O2 at peak (1.38 ± 0.20 vs. 1.90 ± 0.64 L·min−1; p = 0.033). Breathing patterns were similar to those of controls, but acromegalic patients exhibited higher values of V̇E/V̇CO2slope (31.8 ± 3.7 vs. 28.0 ± 2.7; p = 0.018), lower PETCO2 at peak (31.1 ± 5.3 vs. 36.9 ± 3.0 mmHg; p = 0.008), and a greater prevalence of EVin (60

Background:In patients with moderate COPD, response to pulmonary rehabilitation including exercise training varies according to the presence of peripheral muscle fatigue (pMF) of quadriceps. This study investigates the role of pMF in predicting pulmonary rehabilitation outcomes in more severe COPD patients who have already developed chronic respiratory failure (COPD-CRF). Methods:A post hoc analysis of a prospective randomised controlled trial was performed at Istituti Clinici Scientifici Maugeri Lumezzane (Brescia, Italy), involving 30 COPD-CRF patients undergoing a pulmonary rehabilitation programme comprising 20 endurance training sessions. Pre-to-post assessment included a 6-min walk test (6MWT), Fatigue Severity Scale (FSS), Barthel dyspnoea index, and quality-of-life questionnaires. We assessed the contractile pMF of quadriceps via electrical nerve stimulation pre-to-post a cycling fatiguing task, using the change in potentiated quadriceps twitch for pMF. Results:At baseline, 12 (40%) patients developed pMF (pMF group), while 18 (60%) did not (no-pMF group). The pMF group had a lower baseline 6-min walk distance (6MWD) with greater FSS and lower quadriceps thickness. After pulmonary rehabilitation, no change in contractile pMF was found in the overall group, but pMF ameliorated only in the pMF group. The pMF group had a greater increase in 6MWD (71.67±53.64 m versus 35.28±36.01 m, p<0.05) and was more likely to exceed the minimal clinically important difference in 6MWD (OR 6.25, 95% CI 1.05-37.07; p=0.044). Other pulmonary rehabilitation outcomes improved similarly between groups. Conclusion:Baseline quadriceps pMF predicted greater improvement in the 6MWT in COPD-CRF patients, suggesting it may be a new target for predicting pulmonary rehabilitation outcomes and optimising training protocols.

Vascular responsiveness due to passive leg movement (PLM) on the brain remains unknown. This study aimed to evaluate the effects of cold‐induced sympathetic activation (CPT) on femoral and ipsilateral and contralateral carotid arteries' vascular responsiveness evoked by PLM. Thirteen participants (seven males and six females; age: 27.0 ± 2.3 years) undertook a randomized session in which PLM was performed on the right leg at rest and during CPT. Right femoral (fBF) and right (ipsilateral) and left (contralateral) carotid (cBF) blood flows were measured by ultrasounds, and heart hemodynamics were assessed via photoplethysmography and impedance cardiograph. Systolic arterial pressure (SAP) time series were used to infer sympathetic modulation to the vessels. Femoral (fVC) and carotid (cVC) vascular conductance (BF/MAP) were calculated. CPT evoked changes in PLM on cBF, fBF, and fVC (interaction and time effect). cBF peak and cBF and cVC area under the curve were higher in the contralateral carotid in the two interventions. Low‐frequency power of SAP was higher in PLM‐CPT than in PLM; all p < 0.05. These results suggest that the CPT‐induced increases in sympathetic modulation attenuate the vascular responsiveness in the femoral, but not the carotid, arteries. Also, the contralateral carotid increased blood flow during PLM, regardless of the CPT.

Although many studies have investigated whether aerobic training in hypoxia (IHT) could bring advantages to maximal oxygen uptake (V̇O2max) and sea-level performance when compared to analogous normoxic training (NT), the literature results are inconsistent. This variability may come from differences in population, training protocols, hypoxic methods, and potential bias. Therefore, a comprehensive meta-analysis with strict inclusion criteria is needed to assess the effects of aerobic IHT on V̇O2max and performance. This study aims to review previous meta-analyses and analyze all parallel-design studies examining the effect of aerobic IHT compared to NT on V̇O2max and sea-level aerobic performance. Systematic research was conducted following PRISMA guidelines regarding the effects of aerobic IHT on sea-level V̇O2max and performance outcomes. The analysis accounted for characteristics of the population, training protocol, hypoxic environment, and publication details. A total of 35 studies involving 524 participants were included. The analysis showed that IHT, compared to NT, did not significantly improve V̇O2max (p = 0.333), peak power output (p = 0.159), and time to exhaustion (p = 0.410). Subgroup analyses identified no significant differences based on fitness level (p = 0.690) and exercise modality (p = 0.900); however, a publication bias was found (p = 0.004). These results suggest that, despite some enthusiastic findings in the literature, possibly influenced by publication-related biases, aerobic IHT does not offer superior improvement in V̇O2max and performance compared with NT. Therefore, adding hypoxia to aerobic exercise does not enhance training adaptations.

BACKGROUND:Subjects with Long COVID, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), experience a wide range of symptoms, including fatigue and respiratory disturbances, affecting their quality of life. Despite the increasing prevalence of Long COVID, the underlying pathogenic mechanisms remain poorly understood. Extracellular vesicles (EVs) are known to be involved in various processes, such as tissue repair and the transmission of viral particles. However, the specific characteristics and functional roles of EVs derived- from patients with Long COVID (LC-EVs) are poorly characterized. METHODS:To uncover systemic mechanisms underlying Long COVID, we performed a comprehensive characterization of patient-derived extracellular vesicles (EVs) via Nanoparticle Tracking analysis (NTA), Atomic Force Microscopy (AFM), Transmission Electron Microscope (TEM) and flow cytometry. These EVs were applied to lung cells, Mesenchymal Stem Cell (MSCs), Human Umbilical Vein Endothelial Cells (HUVECs) and Aortic Smooth Muscle Cells (ASMCs), revealing stress responses through SESN1, SESN2, and p53 activation. We further assessed mitochondrial respiration to evaluate metabolic dysfunction, and conducted targeted transfection experiments to dissect the molecular pathways involved, shedding light on EV-driven cellular reprogramming. RESULTS:Thus, we observed that Long COVID (LC) patients experienced breathlessness and leg discomfort during exertion. Our data highlighted that LC-EVs induce aberrant RUNX2 expression and activate the p53/p21 pathway in lung cells as well stress responses. Additionally, LC-EVs impair mitochondrial function and cellular adaptability under metabolic stress, reducing maximal respiration and ATP production at high cell densities. Protein interaction analysis showed RUNX2 involvement in key biological processes and post-transcriptional regulation by hsa-miR-204-5p was identified. Finally, LC-EVs also activated stress pathways and increased RUNX2, SESN, p53, and p21 levels in endothelial cells, aortic smooth muscle cells, and mesenchymal stem cells. CONCLUSIONS:In conclusions, these findings provide new insights into the role of extracellular vesicles in Long COVID, revealing their involvement in cellular stress and impaired mitochondrial function.

Background: Mechanical net efficiency ( η net) has proven to be mainly dependent on skeletal muscle mitochondria density. Due to the difficulty of estimating energy expenditure for high-intensity exercise, ηnet was only evaluated for intensities below the lactate (La - ) threshold. Therefore, the aim of this study was to estimate ηnet at high-intensity exercise, to find its main determinants and to compare them to those of moderate-intensity ηnet. Considering the relevance of oxygen delivery and extraction during near-maximal effort, we hypothesized that stroke volume (SV), cardiac output (Q) and net oxidative phosphorylation could be the three main factors influencing the η net for high-intensity exercise. Methodology: On the first day, 14 healthy participants (9 males, 5 females; age 24 ± 3 years) performed an incremental exercise test on a semi-recumbent ergometer to determine the peak oxygen uptake (VO 2max ) and power output (PPO). On the second day, the subjects performed a sub-maximal graded exercise test on the same ergometer with two 6-minute steps at 25% (moderate intensity) and 75% (high intensity) of the PPO. VO 2 and heart rate (HR) were monitored continuously and La - was collected at the end of each step. SV was assessed using cardiac ultrasound during exercise and Q was derived from SV and HR. We considered the last 30 s of each step. η net was calculated as the ratio of mechanical work (converted to kcal·min −1 ) to energy expenditure above the resting metabolism (also converted to kcal·min −1 ). Net expenditure was calculated from the VO2 values. For each step with more than 4.0 mmol·L −1 of La - , the glycolytic contribution was added to aerobic metabolism and estimated considering 3.0 mL·kg −1 of VO 2 for each 1 mmol·L −1 of La - accumulation. On the last day, the subject underwent a muscle biopsy of vastus lateralis to measure the net oxidative phosphorylation capacity (P-L net OX ). Summary of Results: The subject reached a mean PPO of 291±71 W and a VO 2max of 3.65±0.95L·min −1 . η net 25 was 21.7±5.3%, while η net 75 was 17.9±2.9%. HR 25 and SV 25 were 103.8±15.0bpm and 97.1±21.6mL, while HR 75 and SV 75 were 173.2±9.2bpm and 116.4±45.9mL, with the resulting Q 25 and Q 75 of 10.1±2.0 and 22.0±5.1L·min −1 , respectively. P-L net OX was 75.8±22.8pmol·s -1 ·mg -1 . The analyses do not show a correlation between central hemodynamics parameters and η net for either 25% (SV 25 : r = 0.224 and Q 25 : r = 0.220) and 75% of PPO (SV 75 : r = -0.280 and Q 75 : r = 0.390), despite the HR is lower for higher efficiency at 25% of PPO (HR 25 : r =-0.630, p=0.016*; HR 75 : r=-0.280). Conversely, P-L net OX correlates positively with η net 75 (r=0.600; p=0.023*), but not with η net 25 (r=-0.130). Conclusions: Contrary to our hypothesis, these results indicate that central hemodynamics parameters do not influence η net at high exercise intensity. However, mitochondria oxidative capacity positively correlates with high intensity η net. Therefore, high intensity η net is likely a product of peripheral factors related to mitochondria oxidative capacity rather than a consequence of central hemodynamic response. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background and aim: Vascular responsiveness in conduit arteries is highly influenced by the shear rate of blood cells against the endothelium, generating local nitric oxide-mediated vasodilation. This phenomenon is likely influenced by blood viscosity, as it alters shear rates and the degrees of vasodilation. However, it remains unclear whether changes in blood viscosity (BV%) impact vascular responsiveness. Therefore, the objective of the present study was to investigate the acute effects of hemodialysis on BV% and vascular responsiveness. We hypothesized that BV% would progressively increase during hemodialysis sessions and that this acute change would be correlated with a gradual increase in vascular responsiveness, as assessed by flow-mediated dilation (FMD%). Methods: The degree of intradialytic and interdialytic variation of BV% was measured via hematocrit, while vascular responsiveness was determined by the FMD% of the brachial artery in 17 patients receiving maintenance dialysis for at least three months. Both BV% and FMD% were measured at baseline (T0), at 2 hours (T1) and at 4 hours (T2) during the 4-hour dialysis session (HD) and a 4-hour interdialytic period (Sham) Results: At baseline (T0), FMD% was similar for both Sham and HD (2.5 ± 0.1%; 2.9 ± 0.9%). After 2 and 4 hours, FMD% did not change for the Sham (3.0 ± 1.4% and 3.2 ± 1.3%, respectively). However, a progressive and significant increase in FMD% was observed during HD at T1 (6.7 ± 1.4%; p<0.001) and at T2 (7.8 ± 1.3%; p<0.001). A similar trend was noted for BV%, comparable at T0 in Sham (33.8 ± 3.1%) and HD (33.9 ± 3.1%). No notable difference in BV% was observed during the Sham at T1 (33.9 ± 3.2%) and T2 (33.7 ± 3.1%). In contrast, BV% increased at T1 (35.4 ± 3.2%; p<0.001) and T2 (36.9 ± 2.8%; p<0.001) in HD. The changes between BV% and FMD% were significantly correlated during HD (r = 0.45; p = 0.021). Conclusion: In line with our hypothesis, the progressive increase in BV% measured during dialytic session was parallel to the acute increase in vascular responsiveness. These results highlight that shear rate stimulus-response mechanisms are linearly correlated with blood viscosity. As such, BV% should be considered in the precise analysis of vascular responsiveness in both healthy and dialysis populations. This work was partially funded by the Italian Ministry of Research University (MIUR) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Biological sex and muscle fiber type affect muscle relaxation. However, assessments probing the interaction effect are lacking. This study examined whether any difference in transcranial magnetic stimulation (TMS)-induced muscle relaxation results from the interaction effects of biological sex and skeletal muscle fiber properties in (un)fatigued knee extensors. TMS-induced muscle relaxation was assessed in twenty participants (10 females/10 males) before, after a 2-min sustained maximum voluntary isometric contraction, and four times within 8-min of recovery. Vastus lateralis muscle tissue was obtained separately from the participants’ dominant limb. Type I fiber distribution was not different between sexes (females: 53 ± 11

Background: This research investigates quadriceps muscle fatigability (MF) in Chronic Obstructive Pulmonary Disease (COPD) patients with chronic respiratory failure (CRF) at different levels of lung obstruction [severe obstruction (SO) = FEV1 <50% and > 30% versus very severe obstruction (VSO) = FEV1 ≤ 30%]. It explores the relationships between quadriceps MF and lung function, respiratory muscles, and oxygenation status.Methods: A post-hoc cross-over analysis in 45 COPD patients (20 SO and 25 VSO) undergoing long-term oxygen therapy was performed. Delta change in quadriceps maximum voluntary contraction (MVC) (absolute value and percentage) before and after a constant workload was calculated. Associations between quadriceps MF and lung function, respiratory muscles, and gas exchange were examined using Pearson’s correlation and multivariate linear regression analysis.Results: SO patients experience a more substantial reduction in MVC compared to VSO (-15.15±9.13% vs -9.29 ± 8.90%, p=0.0357), despite comparable resting MVC. Dyspnea is more pronounced in VSO at the beginning and end of the exercise. Correlations were found between MF and Maximal Inspiratory Pressure (MIP) (r = -0.4412, p= 0.0056), Maximal Expiratory Pressure (MEP) (r= -0.3561. p=0.0282), and a tendency for FEV1% (r= -0.2931, p= 0.0507). The regression model (R2 = 0.4719) indicates that lower MIP and FEV1 and high total lung capacity are significant factors in reducing quadriceps muscle fatigability after a fatiguing task.Conclusion: COPD patients with more severe pulmonary obstruction and hyperinflation and lower respiratory muscle strength have lower quadriceps MF but higher dyspnoea both at rest and during exercise.