Experimental Physiology最新文献

{"title":"Antenatal betamethasone impairs markers of cardiac development and function in near-term lambs.","authors":"Reza Amanollahi, Ashley S Meakin, Stacey L Holman, Vicki L Clifton, Kent L Thornburg, Michael D Wiese, Kathryn L Gatford, Mitchell C Lock, Janna L Morrison","doi":"10.1113/EP093025","DOIUrl":"https://doi.org/10.1113/EP093025","url":null,"abstract":"<p><p>Antenatal corticosteroids are commonly administered to promote fetal lung maturation; however, their impact on heart development is not well understood. This study therefore investigated the effects of antenatal betamethasone on cardiac development in near-term lambs, using tissues collected from a cohort of ewes with mild experimentally induced asthma. Pregnant ewes received two doses of either saline (Saline) or betamethasone (Betamethasone, intramuscular, 11.4 mg) given 24 h apart, before delivery at 140 days of gestation (term = 150days of gestation). Cardiac protein expression and hormone concentrations in the left ventricle were analysed using western blot and LC-MS/MS, respectively. Fetal and neonatal heart rate and blood pressure were higher in Betamethasone compared to Saline lambs. Betamethasone lambs had lower cardiac concentrations of cortisol, corticosterone, oestradiol, progesterone and thyroxine but a higher triiodothyronine. The protein ratio of glucocorticoid receptor GRβ:GRα-A was higher in the hearts of Betamethasone compared to Saline. Additionally, the expression of insulin-like growth factor 1 receptor (a marker of cardiac proliferative capacity), proliferating cell nuclear antigen (a marker of DNA replication) and the fatty acid transporter CD36 were lower in Betamethasone lambs. These findings suggest that antenatal betamethasone may disrupt normal heart development by altering glucocorticoid receptor isoform expression and reducing cardiac exposure to glucocorticoid and sex hormones. Consequently, this leads to decreased expression of markers associated with cardiac growth and fatty acid uptake. These alterations in heart development caused by antenatal corticosteroids exposure may increase the risk of cardiovascular disease later in life if these changes persist into adulthood.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new method for non-invasive determination of effective pulmonary blood flow and cardiac output in spontaneously breathing subjects.","authors":"Andras Gedeon, Jakob Jansson, David Patrickson, Mats Wallin","doi":"10.1113/EP093079","DOIUrl":"https://doi.org/10.1113/EP093079","url":null,"abstract":"<p><p>The differential Fick method is well established for measuring effective pulmonary blood flow (EPBF) and cardiac output (CO) but until now it has only been used for patients on mechanical ventilation. Here we present and evaluate a new approach adapted to spontaneous breathing situations. Ten healthy subjects with diverse anthropometric and respiratory parameters were studied in the sitting position. Rebreathing through a dead space of precisely known volume and recording the resulting rise in the end-tidal CO₂ value allowed the determination of EPBF. The shunted blood flow fraction was estimated from the arterial oxygen saturation to obtain cardiac output (FickCO). Two measurements were made on each subject 15 min apart. Reference values for cardiac output (RefCO), were calculated as the product of stroke volume and heart rate where the stroke volume was measured with established echocardiography techniques. Heart rate and arterial oxygen saturation were measured with an ordinary pulse oximeter. Comparing FickCO to RefCO using a Bland-Altman analysis, we obtained a mean bias of 0.03 L/min, limits of agreement (LoA) of +1.43 to -1.37 (95% CI) L/min and a percentage error (PE) of 0.25. For the mean of two FickCO observations, we obtained a mean bias of -0.04 L/min, LoA +0.94 to -1.01 (95% CI) and PE of 0.17. The differential Fick method can be adapted to spontaneously breathing situations with good absolute accuracy using simple equipment. Short data collection times make it possible to use the mean of repeated observations and thereby get adequate precision. The new method could therefore be of value both in the pre-operative and the post-operative setting.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fmr1 knockout disrupts multiple intrinsic properties via reduced HCN channel activity in mediodorsal thalamocortical neurons.","authors":"Gregory J Ordemann, Polina Lyuboslavsky, Alena Kizimenko, Audrey C Brumback","doi":"10.1113/EP092894","DOIUrl":"10.1113/EP092894","url":null,"abstract":"<p><p>The neurodevelopmental disorder fragile X syndrome (FXS) results from hypermethylation of the FMR1 gene, which prevents production of the FMRP protein. FMRP modulates the expression and function of a variety of proteins, including voltage-gated ion channels, such as hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, which are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving the mediodorsal thalamus (MD), has been implicated in neurodevelopmental disorders such as FXS. MD connectivity with the medial prefrontal cortex (mPFC) is integral to executive functions such as working memory and social behaviours that are disrupted in FXS. We used a combination of retrograde labelling and ex vivo brain slice whole-cell electrophysiology in 40 wild-type and 42 Fmr1 knockout male mice to investigate how a lack of Fmr1 affects intrinsic cellular properties in lateral (MD-L) and medial (MD-M) MD neurons that project to the mPFC (MD→mPFC neurons). In MD-L neurons, Fmr1 knockout decreased the HCN-mediated membrane properties voltage sag and membrane after-hyperpolarization. We also identified a delay in rebound spike timing in both complex bursts and low-threshold spikes. In Fmr1 knockout mice, reduced HCN channel activity in MD-L→mPFC neurons impaired both the timing and the magnitude of HCN-mediated membrane potential regulation. Changes in response timing might adversely affect rhythm propagation in Fmr1 KO thalamocortical circuitry. MD thalamic neurons are crucial for maintaining rhythmic activity involved in cognitive and affective functions. Understanding specific mechanisms of thalamocortical circuit activity might lead to therapeutic interventions for individuals with FXS and other conditions characterized by thalamic dysrhythmia.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the impact of the cardiovascular system on cerebrovascular health using MRI.","authors":"Ian D Driver, Kevin Murphy","doi":"10.1113/EP092467","DOIUrl":"https://doi.org/10.1113/EP092467","url":null,"abstract":"<p><p>Human cerebrovasculature is finely tuned to enable local changes in blood flow to meet the brain's demands, whilst protecting the brain from systemic changes in blood pressure, both acutely during a heartbeat and chronically over time. This review summarises cerebrovascular structure and function, their role in disease and neurodegeneration and the part MRI measurements can play in probing them. MRI methods to measure various aspects of cerebrovascular physiology are described and placed in context of applications studying cerebrovascular health. The role of the cardiovascular system linking the cardiac pulse wave to cerebrovascular disease and gaps in mechanistic knowledge are highlighted.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression characteristics of dual-specificity phosphatase 2 and hypoxia-inducible factor-1α in acute kidney injury and preliminary study of the effect of dual-specificity phosphatase 2 on HK-2 cells.","authors":"Xueqian Chu, Songmin Xue, Lanyan Lin, Xuan Huang, Sisi Chen, Wulaer Adeli, Zulibiya Tuohetiyaer, Suhua Li, Chen Lu","doi":"10.1113/EP092493","DOIUrl":"https://doi.org/10.1113/EP092493","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is a global health problem with significant long-term harm if the prognosis is poor. Dual-specificity phosphatase 2 (DUSP2) is involved in key regulatory pathways in several disease processes, but its function in renal pathophysiology is unclear. The expression levels of DUSP2 in the peripheral blood of AKI and non-AKI patients were first examined. The expression characteristics of DUSP2 and hypoxia-inducible factor-1α (HIF-1α) in AKI conditions were analysed in renal tissues from AKI patients and different AKI model mice. Human renal tubular epithelial cells (HK-2) were utilized for in vitro experiments to investigate the effects of overexpression of DUSP2 on cell proliferation, apoptosis and HIF-1α levels under hypoxia-reoxygenation conditions. DUSP2 showed low expression in the peripheral blood serum of AKI patients. In the renal tissues of patients and mouse models of AKI, DUSP2 expression was significantly lower, and HIF-1α expression was significantly higher. Under hypoxia-reoxygenation conditions, DUSP2 overexpression promoted HK-2 cell proliferation, inhibited apoptosis and suppressed HIF-1α expression. The present study demonstrated a significant correlation between DUSP2 and HIF-1α expression in the context of AKI and revealed the protective effect of DUSP2 overexpression on renal tubular epithelial cells under hypoxia-reoxygenation, which provides a new better understanding of AKI.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The physiology of survival: Fluid and food.","authors":"Mike Tipton, Hugh Montgomery","doi":"10.1113/EP093194","DOIUrl":"https://doi.org/10.1113/EP093194","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Water and wisdom: Hydration as a defence against dementia.","authors":"David C Byfield, Damian M Bailey","doi":"10.1113/EP093168","DOIUrl":"https://doi.org/10.1113/EP093168","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Commuting by bicycle (vs. by car) is associated with improved aerobic power, microvascular function and diminished CO₂ output in the atmosphere.","authors":"Caterina Ursella, Giovanni Baldassarre, Lucrezia Zuccarelli, Federica Caponnetto, Francesco Curcio, Mattia D'Alleva, Maria De Martino, Elisabetta Fontanini, Andrea Palomba, Antonio Paolo Beltrami, Federico Formenti, Bruno Grassi","doi":"10.1113/EP092636","DOIUrl":"https://doi.org/10.1113/EP092636","url":null,"abstract":"<p><p>The study investigated whether bicycle compared with car commuting, over relatively small distances, has positive effects on physiological variables, cardiometabolic fitness and CO₂ output in the atmosphere. Bike Commuters (11 M, 15 F; age [median value (interquartile range)] 51.5 (38.3-56.8) years; body mass index [BMI] 22.8 (21.0-24.1) kg m^-2) were compared with Car Commuters (12 M, 19 F; age 47.0 (36.0-56.5) years; BMI 23.5 (21.4-24.9) kg m^-2). In a longitudinal arm of the study, 20 Car Commuters were re-evaluated after they switched for 24 weeks to bicycle commuting (Car→Bike Commuters). Measurements included peak aerobic power ( <math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> <annotation>${dot V_{{{mathrm{O}}_2}{mathrm{peak}}}}$</annotation></semantics> </math> ) and ventilatory thresholds on a cycle ergometer, blood flow increase in the common femoral artery during a passive leg movement (PLM) test, energy expenditure and <math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><mi>C</mi> <msub><mi>O</mi> <mn>2</mn></msub> </mrow> </msub> <annotation>${dot V_{{mathrm{C}}{{mathrm{O}}_2}}}$</annotation></semantics> </math> exhaled during commuting. Bike Commuters had higher <math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> <annotation>${dot V_{{{mathrm{O}}_2}{mathrm{peak}}}}$</annotation></semantics> </math> (33.7 (31.3-38.1) versus 25.3 (23.5-28.9) mL kg^-1 min^-1, P < 0.001) and ventilatory thresholds than Car Commuters, higher Δpeak blood flow (+25%, P = 0.04) and area under the blood flow versus time curve (+46%, P = 0.03) during PLM, and an enhanced skeletal muscle oxidative metabolism. <math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> <annotation>${dot V_{{{mathrm{O}}_2}{mathrm{peak}}}}$</annotation></semantics> </math> and PLM variables increased in Car→Bike Commuters. Metabolic CO₂ output during bicycle commuting was ∼12 times less than that for a petrol car. In moderately active individuals, short-distance bicycle commuting at moderate intensity was associated, compared with car commuting, with positive effects on several physiological functions and environmental factors.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seven days of mixed-method heat acclimation improved markers of cardiovascular and fluid-regulatory strain during exercise-heat stress.","authors":"Daniel Snape, Barney Wainwright, Iain T Parsons, Michael J Stacey, David R Woods, John O'Hara","doi":"10.1113/EP092681","DOIUrl":"https://doi.org/10.1113/EP092681","url":null,"abstract":"<p><p>A mixed-method heat acclimation (HA) protocol may optimise performance by supporting the training taper while promoting thermal adaptation; however, the impact on cardiovascular and fluid-regulatory adjustments to protect health is unknown. Therefore, we examined the effects of a mixed-method heat protocol on physiological responses, including cardiovascular and fluid-regulatory strain with exercise-heat stress, and self-paced performance in the heat. Twenty (15 males, five females) triathletes were randomised to 8 days of HA (HOT), or exercise in thermoneutral conditions (TEMP). A heat stress test (HST) comprising 45 min of cycling in a climatic chamber (32°C, 70% relative humidity) was performed on days 1, 5 (HOT only) and 8. Before and after the intervention, a cycling time trial was conducted in the same climatic conditions (days 0 and 10). Venous blood samples were analysed at rest and post-HST (days 1 and 8 only) for the catecholamine product normetanephrine and the vasopressin surrogate copeptin. Following 7 days of HA (days 1 vs. 8) resting rectal temperature was significantly lower in the HOT compared to the TEMP group (-0.32 ± 0.36°C, P = 0.002). Normetanephrine was 24.3% lower after 7 days of HA (P = 0.012), and copeptin was 53.4% lower at the post-HST time point (HOT vs. TEMP, P = 0.012). However, HA had no effect (0.3%, P = 0.984) on self-paced performance in the heat. Mixed-method HA elicited a progressive reduction in cardiovascular strain and a net reduction in fluid-regulatory strain without improving self-paced performance in the heat.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-induced effects on atherogenesis and tryptophan catabolism via the kynurenine pathway in an HIV-associated atherosclerosis mouse model.","authors":"Marcus V S Rangel, Mohammad Afaque Alam, Mohammad Islamuddin, Zheng Chen, Xuebin Qin, Juliana P Borges","doi":"10.1113/EP092744","DOIUrl":"https://doi.org/10.1113/EP092744","url":null,"abstract":"<p><p>A mouse model of HIV-associated atherosclerosis (Tg26^+/-ApoE^-/-) exhibited increased plaque area compared with the ApoE^-/- mouse, linked to elevated indoleamine 2,3-dioxygenase (IDO) activity. IDO catalyses the conversion of tryptophan (TRP) into kynurenine (KYN), measured by the KYN-to-TRP ratio. As a biomarker of inflammation, IDO has been implicated as a risk factor for cardiovascular disease. To investigate the effect of exercise training on atherogenesis and IDO activity in Tg26^+/-ApoE^-/- mice, nine Tg26^+/-ApoE^-/- and 18 ApoE^-/- male mice were fed an atherogenic diet and randomized into exercised or control groups. The exercised groups underwent an 8-week treadmill protocol at moderate intensity (five times per week at 60% maximum velocity). Concentrations of KYN, TRP and cytokines were measured using ELISA, immune expression by flow cytometry, and lipid profile by a biochemistry analyser. Aortas were harvested post mortem for en face analysis. Tg26^+/-ApoE^-/- mice showed ∼40% larger plaques than ApoE^-/- mice (P = 0.01), with slightly higher neutrophil (P = 0.05) and monocyte expression (P = 0.06). Plaque area was reduced by 40% in exercised ApoE^-/- mice (P = 0.04), but by only 12% in exercised Tg26^+/-ApoE^-/- animals (P = 0.85). Exercised Tg26^+/-ApoE^-/- mice showed higher IDO activity than exercised ApoE^-/- mice (58.57% ± 6.88% vs. -4.62% ± 17.20%, P = 0.01), which was positively correlated with plaque area (R = 0.99, P = 0.02). Exercised ApoE-^/- mice showed significantly lower triglyceride levels compared with exercised Tg26^+/-ApoE^-/- mice (75.8 ± 14.8 vs. 165.2 ± 43.6 mg/dL; P = 0.02). Unlike ApoE^-/- mice, moderate-intensity aerobic training did not reduce plaque area in mice with HIV-associated atherosclerosis. Moreover, exercise training appeared to increase inflammation in Tg26^+/-ApoE^-/- mice, as indicated by elevated IDO activity.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}