Journal of Physiology-London最新文献

{"title":"What is next for the ‘muscle memory’ conundrum? Unresolved questions and future research directions","authors":"Igor Longobardi, Jake Cox, Tyler Daubrah-Scott, Pardeep Pabla, Manoel E. Lixandrão","doi":"10.1113/JP289672","DOIUrl":"10.1113/JP289672","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5259-5261"},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxytocinergic signalling in the respiratory parafacial region increases the activity of chemosensitive neurons and respiratory output","authors":"Emmanuel V. Araujo, Phelipe E. Silva, Luiz M. Oliveira, Yingtang Shi, Ana C. Takakura, Daniel K. Mulkey, Thiago S. Moreira","doi":"10.1113/JP287845","DOIUrl":"10.1113/JP287845","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>The retrotrapezoid nucleus, located in the parafacial medullary region (RTN/pFRG), is crucial for respiratory activity and central chemoreception. Recent evidence suggests that neuromodulation, including peptidergic signalling, can influence the CO<sub>2</sub>/H<sup>+</sup> sensitivity of RTN neurons. The paraventricular nucleus of the hypothalamus (PVN) projects to the ventral medullary surface, including the RTN, and is considered the primary source of oxytocin to the brainstem. However the physiological significance of oxytocin signalling in RTN neurons has not been determined. To investigate this further we employed neuroanatomical techniques, slice-patch electrophysiology and <i>in vivo</i> pharmacological and optogenetic tools to characterize the effects of oxytocin on breathing. We found that a subset of PVN excitatory neurons (VGlut2-positive) that project to the RTN (Ctb-positive) are also immunoreactive for oxytocin, suggesting the RTN is a downstream target of these neurons. Exogenous application of the selective oxytocin agonist (TGOT) activates RTN chemoreceptors in a dose-dependent manner (EC<sub>50</sub> = 3 n<span>m</span>), and this response is blunted by the blockade of KCNQ channels (ML252; 10 µM). In urethane-anaesthetized mice pharmacological (TGOT) or optogenetic activation of oxytocinergic receptors/varicosities in the RTN increases breathing amplitude without changing respiratory frequency. These results identify oxytocin signalling to RTN neurons as a novel regulator of respiratory activity and further demonstrate the importance of KCNQ channels in the modulation of RTN neurons.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Key points</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Oxytocin is an important modulator of breathing, including at the level of the retrotrapezoid nucleus (RTN).</li>\u0000 \u0000 <li>The paraventricular nucleus of the hypothalamus (PVN), considered as the primary source of oxytocin in the brainstem, projects to the RTN.</li>\u0000 \u0000 <li>Selective oxytocin agonist (Thr<sup>4</sup>,Gly<sup>7</sup>-oxytocin, TGOT) activates RTN by a mechanism partly dependent on KCNQ channels.</li>\u0000 \u0000 <li><i>In vivo</i>, selective activation of oxytocinergic signalling within the RTN increases breathing amplitude without changing respiratory frequency.</li>\u0000 \u0000 <li>Identifying components of the signalling pathway that couples oxytocin receptor activation to changes i","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5827-5849"},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP287845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial cells in the heart: Implications for their roles in health and disease.","authors":"Svetlana Mastitskaya, Rimma Dugarova, Shefeeq M Theparambil","doi":"10.1113/JP286598","DOIUrl":"https://doi.org/10.1113/JP286598","url":null,"abstract":"<p><p>Glial cells are essential regulators of brain homeostasis by orchestrating neuronal function, metabolism and immune responses. However, much less is known about peripheral glial cells, particularly those in the heart. This review explores the development, types and functions of cardiac glial cells, including Schwann cells, satellite glial cells and recently identified cardiac nexus glia, with some reference to their central nervous system counterparts. The heart's autonomic nervous system consists of sympathetic and parasympathetic nerve fibres, primarily located in the epicardial fat pads within the transverse and oblique sinuses and around the roots of the great vessels. Schwann cells support cardiac repair by myelinating neurons and modulating inflammation, while satellite glial cells regulate the neuronal microenvironment, influencing heart rate and rhythm. Cardiac nexus glial cells interact with both sympathetic and parasympathetic pathways to regulate heart function. Understanding the roles of cardiac glial cells could provide new insights into neuro-cardiac interactions and reveal potential therapeutic targets for cardiac disorders.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The carotid body mediates peak oxygen uptake during maximal physical exertion in rats.","authors":"David C Andrade, Camila Salazar-Ardiles, Camilo Toledo, Cristian Alvarez, Esteban Díaz-Jara, Maria Rodriguez-Fernandez, Gregoire P Millet, Rodrigo Iturriaga","doi":"10.1113/JP288633","DOIUrl":"https://doi.org/10.1113/JP288633","url":null,"abstract":"<p><p>Cardiorespiratory responses to physical exercise are expected to meet the organism's metabolic demands. As carotid body (CB) glomus cells have been proposed as metabolic sensors, we sought to determine their contribution to peak oxygen uptake ( <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> ) during exercise in rats. Adult male Wistar Kyoto rats underwent bilateral co-injection of two adeno-associated viruses (AAVs) at the CB bifurcation (AVV-TH-Cre-SV40 and AVV-hSyn-DREADD(Gi)-mCherry). Clozapine-N-oxide (1 mg/kg, i.p.) was administered to activate the inhibitory DREADD-Gi receptor and suppress CB chemosensory activity. Three weeks after AVV infection we evaluated ventilatory and CB chemosensory responses to sodium cyanide (NaCN), the hypobaric-hypoxic ventilatory response (HHVR), lactate-dependent ventilatory response, arterial blood pressure, exercise performance and <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> . Chemogenetic inhibition of CB glomus cells reduced resting oxygen consumption and ventilatory responses to lactate. In anaesthetized rats acute chemogenetic inhibition of glomus cells markedly diminished the CB chemosensory and ventilatory responses elicited by NaCN, as well as lactate-dependent hyperventilation after CB resection. Similarly HHVR was markedly reduced in non-anaesthetized animals. Notably chemogenetic inhibition of CB glomus cells significantly reduced <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> without altering the time required to reach it. These findings support a novel role for CB glomus cells as metabolic sensors that influence <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> during maximal physical exertion, independent of overall exercise performance. KEY POINTS: Carotid body (CB) glomus cells may function as sensors of metabolic activity through the release of lactate from muscle and its accumulation during physical exertion. CB type I chemoreceptor cells are necessary and play a crucial role in sensing metabolism at rest and during exertion. The CB acts as a metabolic sensor that triggers metabolism during physical exertion, mediating the increment of peak O₂ uptake during exertion, without affecting exercise performance.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury","authors":"Jadwiga N. Bilchak,&nbsp;Simon M. Danner,&nbsp;Guillaume Caron,&nbsp;Marie-Pascale Côté","doi":"10.1113/JP287774","DOIUrl":"10.1113/JP287774","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Within a year after a spinal cord injury (SCI), 75% of individuals develop spasticity. While normal movement relies on the ability to adjust reflexes appropriately, and on reciprocal inhibition of antagonistic muscles, spastic individuals display hyperactive spinal reflexes and involuntary muscle co-contractions. Current anti-spastic medications can suppress uncontrolled movements, but by acting on GABAergic signalling, these medications lead to severe side-effects and weakened muscle force, making them incompatible with activity-based therapies. We have previously shown that pharmacologically enhancing activity of KCC2, a chloride cotransporter, reduces signs of spasticity in anaesthetized chronic SCI rats. Here, we examine the effect of enhancing KCC2 in awake animals, using a battery of tests assessing hyperreflexia in multiple reflex pathways required for normal movement as well as locomotor function. Sprague-Dawley rats were implanted with chronic EMG electrodes bilaterally in ankle flexor and ankle extensor muscles and received a complete spinal transection at T12. Four weeks following SCI, the stretch reflex, the non-nociceptive cutaneous reflex pathway, the flexor withdrawal reflex and the crossed-extensor reflex pathway as well as locomotor function were evaluated before and after receiving the KCC2 enhancer, CLP290. Our results show that enhancing KCC2 activity normalizes reflex responses in multiple pathways and reduces muscle co-contraction without weakening motor output, thereby improving stepping ability. This work reveals the substantial potential for KCC2 enhancers as a novel anti-spastic treatment.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;After chronic spinal cord injury (SCI), the dysregulation of chloride homeostasis and subsequent decrease in spinal inhibition contributes to the development of spastic symptoms.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We previously showed that enhancing the activity of the chloride co-transporter KCC2 after SCI decreases electrophysiological correlates of hyperreflexia and spasticity in deeply anaesthetized animals.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Here, we examine the effect of enhancing KCC2 activity in awake animals on the excitability of multiple spinal reflex pathways required for normal movement including locomotion.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We show that CLP290 decreases hyperreflexia, and reduces muscle co-contraction without weakening motor output, thereby imp","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5701-5721"},"PeriodicalIF":4.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP287774","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncertainty should be the rule, not the exception: Integrating fibre orientation variability in cardiac electrophysiology modelling.","authors":"Ovais Ahmed Jaffery, Caroline Helen Roney","doi":"10.1113/JP289737","DOIUrl":"https://doi.org/10.1113/JP289737","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiotensin-converting enzyme and exercise adaptations: Genetic variability, pharmacological modulation and future directions.","authors":"Tórur Sjúrðarson, Nikolai B Nordsborg","doi":"10.1113/JP288202","DOIUrl":"10.1113/JP288202","url":null,"abstract":"<p><p>Individual responses to exercise training vary widely, shaping athletic performance, rehabilitation outcomes and long‑term health trajectories. This review synthesizes evidence on how angiotensin-converting enzyme (ACE) activity, influenced by genetic variation, epigenetic regulation and pharmacological modulation, shapes adaptations in skeletal muscle hypertrophy, cardiac remodelling, erythropoiesis, endurance capacity and injury susceptibility. We highlight ACE's nuanced role, showing that pharmacological inhibition selectively attenuates cardiac and haematological adaptations, such as haemoglobin mass and lean body mass, without affecting peripheral muscle adaptations and aerobic performance. Additionally, exercise itself modulates ACE expression and the broader renin-angiotensin system signalling network in a context-dependent manner, complicating genotype-phenotype interactions. Future research should move decisively beyond genotype-based stratification and prioritize direct phenotyping of ACE activity, together with comprehensive profiling of the entire renin-angiotensin system axis, as genotype alone poorly predicts enzyme levels or downstream signalling. More broadly, ACE inhibition serves as a mechanistic model for systematically investigating biological pathways underlying individual variability in training responses, advancing precision exercise medicine.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What's so special about the physiology of exercise? This Special Issue!","authors":"Vaughan G. Macefield","doi":"10.1113/JP289385","DOIUrl":"10.1113/JP289385","url":null,"abstract":"&lt;p&gt;Why do papers dealing with exercise feature so prominently in &lt;i&gt;The Journal of Physiology&lt;/i&gt;? Perhaps it is simply because exercise requires so many changes to physiology, that it serves, in its various forms – strong, weak, intermittent, continuous, isometric, isotonic or even imaginary – as a means of interrogating how diverse physiological systems operate, both in isolation and together. Indeed, how the cardiovascular system is engaged during exercise, and how it interacts with control of the working muscles, is an important area of research, covering as it does molecular, cellular, systems and integrative physiology. This Special Issue covers many of these aspects, and builds on a symposium organised by Yoshihiro Kubo – &lt;i&gt;Regulation of cardiovascular and skeletal muscle function during exercise&lt;/i&gt; – at the Federation of Oceanic and Asian Physiological Societies (FAOPS) congress in Deagu, South Korea, on 1–4 November 2023, and a symposium – &lt;i&gt;Neural control &amp; autonomic regulation during exercise: recent innovations&lt;/i&gt; – organised by Satoshi Koba and Marc Kaufman at The International Society for Autonomic Neuroscience (ISAN) meeting held in Birmingham, UK, on 24–27 July 2024. I am very grateful to Yoshihiro and Marc for serving as Reviewing Editors for this Special Issue, with the open call for manuscripts leading to several being submitted &lt;i&gt;de novo&lt;/i&gt;. This is an important feature of our special issues: in addition to invited submissions we open it up to the community to truly reflect the ‘state-of-the-art’ of work in the field. Importantly, the rigour with which Yoshihiro and Marc handled manuscripts meant that only the best made it to publication.&lt;/p&gt;&lt;p&gt;So, here you have it: 21 papers published online over the last year and earlier this year now available in one handy volume for your reading pleasure. Starting at the molecular level, Takeuchi and Matsuoka (&lt;span&gt;2025&lt;/span&gt;) consider how exercise affects the energetics of individual muscle cells in the heart, and the role of mitochondria in calcium release from the sarcoplasmic reticulum. The authors developed a model of the human ventricular myocyte, building in all the features of the known energy-dependent processes involved in excitation–contraction, and investigated how mitochondria located in close proximity to the sarcoplasmic reticulum, facilitate these processes during exercise, particularly via mitochondrial Ca&lt;sup&gt;2+&lt;/sup&gt; uniport activity–RyR. Still in the heart, Phadke et al. (&lt;span&gt;2025&lt;/span&gt;) consider the implications of exercise on the heart in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), in whom atrial arrhythmias also have a high prevalence. Variations in a gene expressed in the desmosomes of the heart, &lt;i&gt;plakophilin-2&lt;/i&gt; (PKP2), feature prominently in this disease, so, using a PKP2 knock-out mouse model, the authors show that despite there being no changes in intracellular Ca&lt;sup&gt;2+&lt;/sup&gt; dynamics or action potential morphology, ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 18","pages":"4917-4919"},"PeriodicalIF":4.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP289385","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply from Ali R. Mani, Cecilia Morandotti, Thomas B. Williams, Amar S. Bhogal, Jo Corbett, Michael J. Tipton and Joseph T. Costello.","authors":"Ali R Mani, Cecilia Morandotti, Thomas B Williams, Amar S Bhogal, Jo Corbett, Michael J Tipton, Joseph T Costello","doi":"10.1113/JP289847","DOIUrl":"10.1113/JP289847","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational modelling of the impact of anatomical changes on ECGs in left ventricular hypertrophy","authors":"Mohammadreza Kariman,&nbsp;Karli Gillette,&nbsp;Matthias A. F. Gsell,&nbsp;Anton J. Prassl,&nbsp;Gernot Plank,&nbsp;Christoph M. Augustin","doi":"10.1113/JP287954","DOIUrl":"10.1113/JP287954","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Left ventricular hypertrophy (LVH) is characterised by an increase in the mass and volume of the left ventricle, typically manifested as ventricular wall thickening and/or dilation. Due to its potential to cause severe, life-threatening complications, ongoing research continues to explore its underlying mechanisms. This study aimed to determine how wall thickening and dilation specifically impact ECG waveforms, isolating these anatomical alterations without considering potential electrophysiological changes associated with LVH – a scenario achievable only through computational modelling. To accomplish this, eccentric and concentric cardiac models – with growth levels from 10% to 100% mass increase – were generated using a kinematic growth, finite element model derived from a healthy control model. Activation sequences were simulated for each model using a pseudo-bidomain reaction-eikonal approach, and 12-lead ECGs were recorded from the hypertrophy models and compared to the control. Results indicated that activation patterns in eccentric hypertrophy models resembled the healthy model, while concentric hypertrophy models displayed substantial deviations. Both types of hypertrophy types led to prolonged QRS durations by up to 21 ms – a 40% increase from baseline – even in the absence of electrical remodelling. Eccentric hypertrophy increased amplitudes in precordial leads, minimally affecting limb leads, while concentric hypertrophy impacted all 12 leads with varied amplitude changes. Leads aVL, V1 and V5/V6 emerged as the most sensitive to anatomical changes. These findings could enhance the accuracy of LVH diagnosis using ECGs, offering a cost-effective strategy to complement clinical evaluation and imaging, ultimately improving LVH detection and management.\u0000\u0000 &lt;figure&gt;\u0000 &lt;div&gt;&lt;picture&gt;\u0000 &lt;source&gt;&lt;/source&gt;&lt;/picture&gt;&lt;p&gt;&lt;/p&gt;\u0000 &lt;/div&gt;\u0000 &lt;/figure&gt;\u0000 &lt;/div&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Key points&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Computational simulations revealed distinct effects of anatomical changes in eccentric and concentric left ventricular hypertrophy on 12-lead ECG signals.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Eccentric hypertrophy primarily affected the precordial leads, showing notable voltage amplitude increases across all precordial lead measurements.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Concentric hypertrophy affected all 12 leads without a clear pattern of amplitude change, displaying both increases and decreases.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Both eccentric and concentric hypertrophy resulted in a consistent prolongation of the QRS complex, ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 19","pages":"5387-5413"},"PeriodicalIF":4.4,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://physoc.onlinelibrary.wiley.com/doi/epdf/10.1113/JP287954","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144976890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}