Experimental Physiology最新文献

{"title":"Increasing paced heart rate reduces cerebral pulsatility.","authors":"A J S Webb, J Thomas, O Llwyd, N Herring","doi":"10.1113/EP094034","DOIUrl":"10.1113/EP094034","url":null,"abstract":"<p><p>Cerebral pulsatility is a key index of cerebral haemodynamics, a central determinant of intravascular shear stress within intracranial vessels, and is associated with cerebral small vessel disease. It increases with a spontaneously falling heart rate, but the effect of altering heart rates on cerebral haemodynamics is unknown. We therefore tested whether increasing paced heart rate would reduce middle cerebral artery Gosling's pulsatility index (PI)on transcranial ultrasound, during emergency or elective implantation of a pacemaker for bradycardia. In 20 participants (14 males, mean age 78), paced heart rate was increased from 50 bpm or the individual's resting heart rate up to 100 bpm in 10 bpm increments. Cerebral pulsatility was strongly and inversely associated with heart rate, with an average reduction in PI of 0.07 per 10 beats per minute in unadjusted analyses, and 0.08 in mixed effects linear models adjusted for age, sex and cardiovascular risk factors (P < 0.001). Increasing heart rate reduced peak systolic velocity by 2.51 cm/s per 10 bpm and increased end-diastolic velocity by 1.26 cm/s per 10 bpm, which both mediated the effect on cerebral pulsatility. However, there was no effect on mean velocity. The decrease in peak systolic middle cerebral artery velocity was linear with increasing heart rate, but end-diastolic velocity was maximal at a heart rate of 80 bpm. Overall, cerebral pulsatility was inversely and causally associated with paced heart rate. Heart rate modification could be a potential intervention to modify cerebral pulsatility, particularly in the context of bradycardia induced by heart block.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Thermo-tone: A newly revealed mechanism of blood flow regulation.","authors":"Thieu X Phan, Gerard P Ahern","doi":"10.1113/EP093562","DOIUrl":"10.1113/EP093562","url":null,"abstract":"<p><p>Myogenic tone enables dynamic control of tissue blood flow. This intrinsic property of vascular smooth muscle cells to sense stretch and reflexively adjust the calibre of small arteries is crucial to maintain capillary pressure and a blood flow reserve. For over 120 years blood pressure was considered the sole determinant of myogenic tone. Our recent research reveals an equal, critical role for temperature. This property, termed 'thermo-tone', renders the tone of arteries strictly heat dependent with thermosensitivities tuned close to resting tissue temperatures (25-37°C). Here, we discuss the underlying signalling mechanisms and the potential role for thermo-tone in the homeostatic regulation of blood flow.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From maturation to degeneration: Distinct biological trajectories in bicuspid and tricuspid aortopathy.","authors":"Riaz Akhtar, Daniel Olaf Riley, Jillian Madine, Mark Field","doi":"10.1113/EP092864","DOIUrl":"10.1113/EP092864","url":null,"abstract":"<p><p>Ascending thoracic aortic aneurysm formation differs fundamentally between patients with bicuspid (BAV) and tricuspid (TAV) aortic valve phenotypes, yet current clinical management largely relies on shared diameter thresholds, although clinical and scientific data fail to correlate with diameter and risk of rupture. Over the past two decades, histological, biochemical and biomechanical studies have revealed unique differences between dilated tissue properties from patients with BAV- and TAV-associated idiopathic degenerative ascending aortic aneurysms even at similar aortic diameters. This review focuses on histological, biochemical and biomechanical differences between BAV and TAV aortopathy with a focus on ageing. Idiopathic degenerative TAV aortopathy is characterised by medial degeneration with elastic lamellar fragmentation and loss, smooth muscle cell depletion, medial fibrosis, mucoid extracellular matrix accumulation and inflammatory features. These degenerative changes correlate with ageing and, in region-specific mechanical testing, with reduced delamination resistance and age-dependent biomechanical weakening. In contrast, BAV aortopathy frequently demonstrates relative preservation of medial architecture despite similar dilatation, alongside altered collagen maturation, and distinct osteogenic/microcalcification signatures. Lifespan analyses indicate that TAV follows a maturation-stabilisation-degeneration trajectory, whereas BAV exhibits aberrant vascular maturation without a true stabilisation phase. Importantly, aortic diameter correlates poorly with histological severity or biomechanical vulnerability, particularly in BAV. Collectively, these data support the concept that ascending thoracic aortic aneurysms in BAV and idiopathic degenerative TAV patients represent biologically divergent aortopathies requiring phenotype-informed risk stratification beyond diameter alone.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance-trained young men exhibit enhanced carotid vasoreactivity during the cold pressor test.","authors":"Ian Hornby-Foster, Cory T Richards, Aimee L Drane, Freya M Lodge, Michael Stembridge, Rachel Lord, Zaheer Yousef, Keeron Stone, Barry J McDonnell, Christopher J A Pugh","doi":"10.1113/EP093966","DOIUrl":"https://doi.org/10.1113/EP093966","url":null,"abstract":"<p><p>The function of the common carotid artery (CCA) is integral to the regulation of cerebral perfusion. Although endurance training is associated with consistent vascular benefits, the effects of resistance training on CCA function are unclear. The cold pressor test (CPT) assesses CCA vasoreactivity via sympathetic stimulation, with peak CCA vasoreactivity (CAR%_peak) reflecting integrated endothelial-autonomic vascular function. In this study, we compared CAR%_peak during the CPT in resistance-trained and untrained young men and examined associations with CCA stiffness and haemodynamics. CCA ultrasound was performed in 10 resistance-trained [24 years (95% confidence interval: 22,26)] and 10 untrained [24 years (22,25)] men at baseline, during a 3-min CPT and after recovery, with simultaneous haemodynamic assessment via finger plethysmography. CAR%_peak was defined as the maximal percentage increase in mean diameter from baseline. Secondary outcomes included CCA stiffness indices and haemodynamics. Both groups exhibited CCA vasodilatation during CPT; however, CAR%_peak was greater in resistance-trained men (P = 0.046). The resistance-trained group also displayed greater increases in systolic diameter at end-CPT (P = 0.033), alongside attenuated pulse pressure (P = 0.050; η² _p = 0.201) and β₁-stiffness (P = 0.041) responses during CPT. CAR%_peak was negatively correlated with baseline β₂-stiffness in resistance-trained men (r = -0.655; P = 0.040), whereas in untrained control subjects it was positively correlated with peak pulse pressure (r = 0.677; P = 0.031). In conclusion, resistance-trained young men exhibit enhanced CCA vasoreactivity and attenuated pulse pressure and stiffness responses to sympathetic stimulation, reflecting favourable adaptations in endothelial-autonomic vascular regulation. These findings highlight the potential of resistance training to improve central vascular function in early adulthood.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ageing, women's health and personalised medicine: Advancing artificial intelligence and therapeutics through the blueprint theory paradigm.","authors":"Rosie Richardson, Tina Woods, Nikodem Grzesiak, Annalisa Jenkins, Carina C Kern","doi":"10.1113/EP092854","DOIUrl":"10.1113/EP092854","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent hypoxia interventions for inducing ventilatory acclimatization to high altitude?","authors":"Martin Burtscher, Axel Kleinsasser, Johannes Burtscher, Katharina Hüfner, Erik R Swenson, Peter Hackett, Hannes Gatterer","doi":"10.1113/EP093689","DOIUrl":"https://doi.org/10.1113/EP093689","url":null,"abstract":"<p><p>Accumulation of ∼200 h of hypoxia exposure (pre-acclimatization) has been suggested to prevent the development of acute mountain sickness when a person is subsequently exposed to high altitude. These pre-exposures are typically undertaken intermittently at or near the place of residence, primarily during sleep in hypoxic tents, and are likely to induce effective ventilatory acclimatization. However, the physiological consequences of different modes of intermittent hypoxia (IH) exposure on ventilatory acclimatization remain largely obscure and are the subject of much controversy. The aim of this review is therefore to summarize and discuss the findings of relevant studies and draw on our long-term practical experience to address the effects of IH exposure on ventilatory acclimatization and to provide suggestions for effective pre-acclimatization. We provide a balanced overview of studies investigating the effects of different types of altitude/hypoxia exposure on the hypoxic ventilatory response and renal compensation to hyperventilation-induced respiratory alkalosis. Although it has been demonstrated convincingly that the hypoxic ventilatory response can increase by 50%-100% with only a few short IH sessions (1 h per day for 7 days), the available data on the effects of IH on renal compensation do not permit definitive conclusions to be drawn. Long-term exposure to IH over several weeks appears to induce renal compensation effectively, allowing for a full ventilatory response and favourable oxygenation at high altitude. To clarify definitively which strategies are most suitable, long-term systematic investigations of various IH strategies are urgently needed.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic stress exacerbates Ca²⁺ dysregulation and arrhythmias in catecholaminergic polymorphic ventricular tachycardia.","authors":"Valeria Gomez, Arpita Deb, Zhuoxin Li, Yujia Cheng, Benjamin K Fischer, Jinying Yang, Jeongmin Lee, Bjorn C Knollmann, Zhiyong Cheng, Bin Liu","doi":"10.1113/EP094053","DOIUrl":"https://doi.org/10.1113/EP094053","url":null,"abstract":"<p><p>Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic arrhythmic syndrome caused by mutations in the sarcoplasmic reticulum (SR) calcium (Ca²⁺) release channel RyR2 or its accessory proteins, including calsequestrin-2 (CASQ2). RyR2 dysfunction or leak is the hallmark feature of CPVT and directly triggers arrhythmias. Despite this electrical instability, CPVT hearts are typically anatomically normal and lack pathological remodelling. Therefore, we hypothesized that introducing additional stressors, such as metabolic stress, would worsen cardiac arrhythmias and potentially trigger pathological remodelling. To test this hypothesis, metabolic stress was introduced by crossbreeding a CPVT model of CASQ2^-/- mice with the Akita mouse, a genetic model of diabetes that also lacks cardiac remodelling. We found that dysregulation of myocyte Ca²⁺ handling was exacerbated in Akita-CASQ2^-/- cells, which exhibited slower Ca²⁺ transient decay kinetics and increased arrhythmogenic Ca²⁺ waves. Akita-CASQ2^-/- mice also displayed more severe arrhythmias, diastolic dysfunction, and cardiac hypertrophy, but without evidence of fibrosis, cell death, or worsened metabolic dysfunction. Finally, mitochondrial reactive oxygen species production was increased in Akita-CASQ2^-/- cardiomyocytes, which may contribute to the more severe pathological phenotype. Overall, our results suggest that metabolic stress can aggravate dysregulated myocyte Ca²⁺ handling and promote cardiac dysfunction in CPVT hearts.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stable isotope-derived measurements of protein synthesis detect amino acid-induced anabolism in skeletal muscle microtissues not captured by puromycin labelling.","authors":"Yekaterina Tiper, Cassidy T Tinline-Goodfellow, Penney M Gilbert, Daniel R Moore","doi":"10.1113/EP094100","DOIUrl":"https://doi.org/10.1113/EP094100","url":null,"abstract":"<p><p>Skeletal muscle microtissues are valuable in vitro models for studying the stimuli regulating muscle protein synthesis (MPS), the key determinant of changes in muscle mass. Differentiated between opposing posts, microtissues contain aligned, contractile myotubes, providing a controlled system for investigating the responses of skeletal muscle to nutrient and contractile stimulation. However, microtissue MPS responses to these stimuli remain under-characterized. Stable isotope-labelled amino acid tracers deliver sarcoplasmic and myofibrillar fractional synthetic rates (FSR) for MPS in human studies but have not been implemented in engineered skeletal muscle. We close these gaps by characterizing amino acid (AA), ketone and contraction-induced MPS in 3D microtissues and 2D myotubes (without contraction) derived from the same primary myoblast line, using stable isotope tracers and puromycin incorporation. Following 4 h of AA withdrawal microtubes and myotubes underwent 2 h of acute AA and/or ketone treatment (±contraction in microtissues). In microtissues, sarcoplasmic FSR increased significantly during amino acid re-addition (P < 0.0001), whereas myofibrillar FSR displayed a main effect of condition (P = 0.0018), with an overall lesser magnitude of change compared to the sarcoplasmic fraction. However, both fractions were unresponsive to ketone stimulation, and the selected contraction regime (when combined with ketones and/or AA; all P ≥ 0.985). 2D myotubes showed significant increases in sarcoplasmic and myofibrillar FSR in response to amino acid treatment (both P ≤ 0.0003). Notably, microtissues demonstrated a more stable myofibrillar protein fraction, with a sarcoplasmic-to-myofibrillar FSR ratio of ∼2:1 which closely resembled that of native human muscle. The puromycin-based approach only detected subtle differences in 2D myotubes (main effect P = 0.031) with AA provision being greater than ketones (P = 0.0196) with no other post hoc differences (all P ≥ 0.221). Puromycin failed to detect MPS responses to any stimulus in microtissues (all P ≥ 0.834), highlighting the greater sensitivity of tracer-based measurements, particularly where longer time scales are needed to capture an effect. These findings support the use of engineered muscle and isotope-derived measurements of MPS in future studies of stimuli regulating skeletal muscle mass.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654187/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise intolerance and impaired aerobic capacity in heart transplant recipients.","authors":"Fred W Kolkhorst, Daniel T Cannon, Harry B Rossiter","doi":"10.1113/EP093964","DOIUrl":"10.1113/EP093964","url":null,"abstract":"<p><p>Heart transplant recipients exhibit reduced exercise tolerance and persistently diminished aerobic capacity despite exercise training. Exercise tolerance depends on integrated oxygen transport and utilization, which are impaired in heart transplant recipients. We synthesize evidence supporting that the combined effects of impaired pulmonary gas exchange, reduced haemoglobin concentration, heart denervation, chronic calcineurin inhibition, decreased muscle capillary density, and detraining from limited physical activity contribute to: (1) reduced pulmonary diffusion and alveolar ventilation-perfusion mismatch that contribute to hypoxemia and increased ventilatory demand; (2) impaired convective oxygen delivery due to anaemia and to heart denervation that limits cardiac output; (3) deficits in endothelial function and reduced muscle capillarization that contribute to diminished convective and diffusive oxygen transport within skeletal muscle. Using Wagner's model, which describes oxygen transport from the atmosphere to muscle mitochondrion, we develop the hypothesis that the persistent reduction in aerobic capacity in heart transplant recipients reflects the combined and interactive effects of impaired convective oxygen transport and reduced muscle oxygen diffusive capacity, rather than a single dominant limitation. This basis generates testable physiological targets for interventions aimed at improving functional capacity after transplantation.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous ketosis in breath-hold diving: Promise, paradox and physiological risk.","authors":"Ivan Drviš, Myrthe Stalmans, Dario Vrdoljak, Nikola Foretic, Damian M Bailey, Željko Dujić","doi":"10.1113/EP094163","DOIUrl":"10.1113/EP094163","url":null,"abstract":"<p><p>Exogenous ketosis induced by ketone ester (KE) ingestion has attracted growing interest as a potential strategy to enhance physiological tolerance to reduced O₂ availability. Reported benefits arise largely from KE-induced hyperventilation, which can improve systemic and tissue oxygenation during altitude exposure and hypoxic exercise, potentially complemented by favourable effects on cellular bioenergetics. Whether these responses translate to breath-hold diving, however, remains unknown. Breath-hold performance is constrained by the integrated effects of progressive hypoxaemia, CO₂ accumulation, acid-base disturbance, altered cerebrovascular regulation and chemoreflex-mediated respiratory drive. Because ventilation ceases during apnoea, interventions that alter pre-apnoeic acid-base status or CO₂ signalling might modify the chemical, neural and perceptual stimuli underlying the urge to breathe without slowing O₂ depletion. Safety therefore depends not only on preserving cerebral O₂ delivery, but also on maintaining the chemoreflex and perceptual warning signals that ordinarily precede hypoxic loss of consciousness. This review evaluates whether the established physiological effects of KE are mechanistically compatible with the unique demands of apnoea, focusing on acid-base regulation, CO₂-dependent cerebrovascular control, autonomic integration and training-related adaptations in elite freedivers, including reduced chemoreflex sensitivity and enhanced cortical control of respiratory drive. We propose that benefits observed during maintained ventilation might not translate to breath-hold diving and could create a mechanistic mismatch with uncertain consequences for performance and safety. Direct apnoea-specific studies are required to determine whether KE supplementation is beneficial, neutral or harmful.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}