Journal of Physiology-London最新文献

{"title":"Unravelling the complexity of respiratory involvement in Duchenne muscular dystrophy: An urgent call for a collective translational approach","authors":"Federica Trucco, Ken D. O'Halloran","doi":"10.1113/JP288810","DOIUrl":"10.1113/JP288810","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 11","pages":"3263-3267"},"PeriodicalIF":4.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192366","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":"Functional sympatholysis of neuropeptide Y-mediated vasoconstriction in humans","authors":"Denis J. Wakeham, Sarah L. Hissen, James P. MacNamara, Scott L. Davis, Paul J. Fadel, Benjamin D. Levine, Christopher M. Hearon Jr","doi":"10.1113/JP288412","DOIUrl":"10.1113/JP288412","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 \u0000 <div>Metabolic inhibition of sympathetic vasoconstriction (functional sympatholysis) is essential for adequate perfusion of skeletal muscle during exercise. Neuropeptide Y (NPY) is a neurotransmitter that elicits potent vasoconstriction and is co-released with noradrenaline during sympathoexcitation. NPY is released from sympathetic nerves during exercise; however, no study has assessed whether NPY-mediated vasoconstriction is sensitive to metabolic inhibition in humans. We tested the hypothesis that post-junctional NPY-mediated vasoconstriction would be sensitive to metabolic inhibition during handgrip exercise to a similar degree as α<sub>1</sub>-adrenergic vasoconstriction. In 12 healthy adults (seven male, age: 30 ± 7 years, body mass index: 24.9 ± 3 kg/m<sup>2</sup>) we measured forearm blood flow (Doppler ultrasound), blood pressure (brachial artery catheter) and heart rate, and calculated changes in forearm vascular conductance (FVC) to local intra-arterial infusions of phenylephrine (PE; α<sub>1</sub>-agonist) or NPY (Y1R-agonist) during: (1) intra-arterial infusion of sodium nitroprusside (SNP; nitric oxide donor), a non-metabolic vasodilatory control, and (2) dynamic rhythmic handgrip exercise (EX; 15% maximal voluntary contraction). As expected, the vasoconstrictor response to PE was attenuated during handgrip exercise compared to SNP (ΔFVC: SNP: −44 ± 25% <i>vs</i>. EX: −17 ± 9%; <i>P</i> = 0.002). Similarly, NPY-mediated vasoconstriction was blunted during handgrip exercise compared to SNP (ΔFVC: SNP: −32 ± 22% <i>vs</i>. EX: −11 ± 7%; <i>P</i> = 0.029). There was no difference in the magnitude of sympatholysis between PE and NPY (PE: 68 ± 18 <i>vs</i>. NPY: 52 ± 34%; <i>P</i> = 0.28). NPY-mediated vasoconstriction is sensitive to metabolic inhibition in humans, and the magnitude of sympatholysis is not different from α<sub>1</sub>-adrenergic vasoconstriction.\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>Neuropeptide Y (NPY) is a neurotransmitter that is co-released from sympathetic nerve terminals and elicits potent vasoconstriction, particularly during periods of sympathoexcitation.</li>\u0000 \u0000 <li>NPY is released from sympathetic nerves during exercise, but it is currently unclear whether NPY-mediated vasoconstriction is sensitive to metabolic inhibition in humans (i.e. functional sympatholysis).</li>\u0000 \u0000 <li>For the first time we have shown that NPY-mediated vasoconstriction is sensitive to meta","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 11","pages":"3329-3340"},"PeriodicalIF":4.7,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP288412","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192445","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":"Increased muscle satellite cell content and preserved telomere length in response to exercise training in FSHD: implications for sarcopenia and longevity","authors":"Sofia Germano Travieso, Gabriela Ueta Ortiz","doi":"10.1113/JP288768","DOIUrl":"10.1113/JP288768","url":null,"abstract":"","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 11","pages":"3279-3280"},"PeriodicalIF":4.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182830","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":"Pulmonary arterial mechanoreceptors modulate exercise-induced sympathetic activation in healthy humans during moderate-intensity hypoxic exercise.","authors":"Michiel T Ewalts, Thomas D Griffiths, Andrew J M Douglas, Elliott J Jenkins, Guto Wyn Hughes, Craig D Steinback, Lydia L Simpson, Samuel J Oliver, Mike Stembridge, Jonathan P Moore","doi":"10.1113/JP288128","DOIUrl":"https://doi.org/10.1113/JP288128","url":null,"abstract":"<p><p>Central command, muscle afferent feedback and arterial baroreceptors all contribute to sympathetic vasoconstrictor activity during moderate-intensity dynamic exercise in humans; however, whether a causal link exists between pulmonary arterial mechanoreceptors and sympathetic outflow directed to inactive skeletal muscle (muscle sympathetic nerve activity, MSNA) remains to be explored. Twelve participants (28 ± 7 years, 2 females) performed two 6 min exercise bouts (heart rate ∼ 120∙beats∙min^-1) in hypoxia (FiO_2 =12.5%) to elevate pulmonary artery pressure (PAP) above normal, whilst MSNA (microneurography), systemic blood pressure (photoplethysmography, BP), oxygen saturation (SpO₂) and minute ventilation (V_E) were measured continuously. Systolic PAP was estimated using Doppler echocardiography. In one trial nitric oxide was added to the inhaled air (iNO, 40 parts per million) to selectively dilate the pulmonary vasculature and reduce exercise PAP. MSNA burst frequency was supressed (30 ± 9 vs. 34 ± 9 bursts∙min^-1; p = 0.03) when exercise systolic PAP was lowered (36.8 vs. 42.9 ± 8 mmHg; p = 0.02). MSNA burst incidence (index of sympathetic baroreflex operating point) was reduced (25 ± 8 vs. 28 ± 9 bursts∙100 heartbeats^-1; p = 0.03) without any change in corresponding diastolic BP or spontaneous baroreflex gain. Mean BP, SpO₂ and V_E did not differ between trials. Together these data support a mechanistic link between pulmonary arterial mechanoreceptor activation and neurocirculatory control during hypoxic exercise. The effect of pulmonary arterial mechanoreceptor activity on exercise-induced sympathetic activation and baroreflex resetting may have consequences for sympathetic vasomotor outflow (dys)regulation in health and disease where PAP is elevated. KEY POINTS: Pulmonary arterial pressure increases proportionally to cardiac output during dynamic exercise; this pressure rise may contribute to excitation of sympathetic vasoconstrictor activity directed to skeletal muscle (muscle sympathetic nerve activity, MSNA) via stimulation of pulmonary arterial mechanoreceptors. In this study addition of nitric oxide to hypoxic inspired air (FiO₂ = 12.5%) reduced pulmonary arterial pressure during sub-maximal cycling exercise; this coincided with reduced MSNA burst frequency (vasoconstrictor outflow) and burst incidence (operating point for baroreflex control of vasoconstrictor outflow). These findings demonstrate that a signal from pulmonary arterial mechanoreceptors is involved in sympathoexcitation during hypoxic exercise. Furthermore this mechanism could be relevant clinically in pulmonary and cardiac diseases associated with pulmonary hypertension and exaggerated sympathoexcitation during exercise.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181230","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":"When pain is not the same: baroreceptor activation delineates chronic pain and pain-free participants’ perception and modulation of noxious pressure","authors":"Luke A. Henderson","doi":"10.1113/JP287685","DOIUrl":"10.1113/JP287685","url":null,"abstract":"&lt;p&gt;Investigations into the perception and modulation of pain often focus on ascending and descending pain pathways, those which form direct nociceptive relays, rather than considering the swathe of physiological processes which are also entwined and govern our overall pain percept. Whilst there are numerous studies exploring the integration of acute pain and autonomic activity (e.g. Burton et al., &lt;span&gt;2009&lt;/span&gt;), which is vital for defensive behaviour expression, few studies have explored the integration of autonomic function with chronic pain. Throughout their publication, Venezia et al. (&lt;span&gt;2024&lt;/span&gt;) not only acknowledge, but probe into how the autonomic nervous system (ANS) is involved in the perception and modulation of pain, both in chronic pain sufferers and in pain-free individuals.&lt;/p&gt;&lt;p&gt;Their findings reveal a fundamental difference in how activation of the ANS, through baroreceptor stimulation, alters perceived pain between chronic pain sufferers and those without pain, with their stimulation technique increasing and decreasing pain, respectively. Moreover, by conducting a conditioned pain modulation (CPM) task, a method for activating the brain's descending analgesic system also known as the ‘pain inhibits pain’ phenomenon, the authors demonstrate how resting tone of the ANS is directly linked to the magnitude of CPM expressed whilst conducting baroreceptor stimulation.&lt;/p&gt;&lt;p&gt;Venezia and colleagues present an elegant design, including a large sample size, to investigate behavioural effects (22 chronic pain; 29 no pain). Across a single study session, where autonomic activity (heart rate and blood pressure) was measured continuously, participants underwent a pressure pain calibration protocol to first adjust to inter-individual differences in pain thresholds, before undertaking an autonomic baseline, autonomic stress and pain task where, whilst pressure pain was delivered to the right fingernail, either sham or active baroreceptor stimulation occurred through suction of the left and right carotid bifurcation. During a final task period, pain was first delivered on a longer time scale to the left fingernail, before a short-lasting pressure pain was delivered simultaneously to the right fingernail, triggering the CPM response.&lt;/p&gt;&lt;p&gt;With particular interest being placed in recent years in uncovering biomarkers to chronic pain persistence and magnitude, the findings presented by Venezia and colleagues provide a unique lens into the underlying pathophysiology of chronic low back pain. Specifically, they identify relationships between resting blood pressure and the intensity of reported pain both at the time of undertaking the experimental session and over the preceding year prior. These relationships, whilst novel, are supported through the prominent theory that chronic pain states are driven through dysfunction in brainstem circuitry (Mills et al., &lt;span&gt;2018&lt;/span&gt;), with these same circuits playing a core role in ANS functions ","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 11","pages":"3275-3276"},"PeriodicalIF":4.7,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287685","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183650","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":"Correction to ‘Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism’","authors":"","doi":"10.1113/JP289227","DOIUrl":"10.1113/JP289227","url":null,"abstract":"<p>Carneiro-Ramos, M. S., Diniz, G. P., Almeida, J., Vieira, R. L. P., Pinheiro, S. V. B., Santos, R. A., &amp; Barreto-Chaves, M. L. M. (2007). Cardiac angiotensin II type I and type II receptors are increased in rats submitted to experimental hypothyroidism. <i>The Journal of Physiology</i>, <i>583</i>(1), 213–223. https://doi.org/10.1113/jphysiol.2007.134080</p><p>This correction seeks to clarify certain aspects of the original article. First, it clarifies that representative loading controls (β-actin and α-actinin) were reused across multiple figures in the original article. Representative β-actin loading controls were reused in Figs 2B, 3A and 3B, and representative α-actinin loading controls were reused in Figs 4A and 4B, and 6A and 6B. This was scientifically valid, but was not made explicitly clear in the original article.</p><p>The authors also acknowledge the fact that splicing of the AT2 gel in Fig. 6B was not disclosed, whereas the corresponding loading control gel was not spliced. This implies that the representative images for the analyte of interest and the loading control could not have been derived from the same sample. However, despite this error, the relevant conclusions were based on summary data across a number of experiments and thus are unaffected.</p><p>This notice also highlights that the β-actin loading control band from the left ventricle sample, shown on the right side of Fig. 2B, was mistakenly also used as a representative image from the right ventricle sample, shown on the left side of Fig. 2B. However, this error does not affect the conclusions of the article.</p><p>The authors apologise for these errors and omissions.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 11","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP289227","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180219","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":"Startling acoustic stimuli hasten reflexive choice reaching tasks by enhancing, but not changing the timing of, express visuomotor responses","authors":"Vivian Weerdesteyn,&nbsp;Sarah L. Kearsley,&nbsp;Aaron L. Cecala,&nbsp;Ewan A. Macpherson,&nbsp;Brian D. Corneil","doi":"10.1113/JP287252","DOIUrl":"10.1113/JP287252","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 \u0000 &lt;div&gt;Responding to an external stimulus takes ∼200 ms, but this can be shortened to as little as ∼120 ms with the additional presentation of a startling acoustic stimulus. This phenomenon is hypothesized to arise from the involuntary release of a prepared movement (a &lt;i&gt;StartReact&lt;/i&gt; effect). However, a startling acoustic stimulus also expedites rapid mid-flight, reactive adjustments to unpredictably displaced targets which could not have been prepared in advance. We surmise that for such rapid visuomotor transformations, intersensory facilitation may occur between auditory signals arising from the startling acoustic stimulus and visual signals relayed along a fast subcortical network. To explore this, we examined how a startling acoustic stimulus shortens reaction times in a task that produces express visuomotor responses, which are brief bursts of muscle activity that arise from a fast tectoreticulospinal network. We measured express visuomotor responses on upper limb muscles in humans as they reached either toward or away from a stimulus in blocks of trials where movements could either be fully prepared or not, occasionally pairing stimulus presentation with a startling acoustic stimulus. The startling acoustic stimulus reliably produced larger but fixed-latency express visuomotor responses in a target-selective manner, and also shortened reaction times, which were equally short for prepared and unprepared movements. Our results provide insights into how a startling acoustic stimulus shortens the latency of reactive movements without full motor preparation. We propose that the reticular formation is the probable node for intersensory convergence during the most rapid transformations of vision into targeted reaching actions.\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;A startling acoustic stimulus (SAS) shortens reaction times by releasing fully prepared motor programmes (the &lt;i&gt;StartReact&lt;/i&gt; effect), but can also hasten responses in reflexive tasks without any movement preparation.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Here we measure the effect of a SAS on reaction times and upper limb muscle recruitment in a reflexive reaching task, focusing on express visuomotor responses that are evoked by visual target presentation and demarcate activity along a subcortical tectoreticulospinal pathway.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;A SAS robustly increased the magnitude of express visuomotor responses without changing their timing, and this increase was ti","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":"603 11","pages":"3425-3444"},"PeriodicalIF":4.7,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1113/JP287252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180579","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":"Fetal glucose availability: a key regulator of the metabolic, hormonal and contractility profiles of the fetal sheep heart.","authors":"Melanie R Bertossa, Jack R T Darby, Stacey L Holman, Steven K S Cho, Ashley S Meakin, Mitchell C Lock, Jordan A Minns, Michael D Wiese, Christopher K Macgowan, Mike Seed, Janna L Morrison","doi":"10.1113/JP288303","DOIUrl":"https://doi.org/10.1113/JP288303","url":null,"abstract":"<p><p>There is an association between fetal growth restriction (FGR) and a poor lifetime cardiac health trajectory. Defining the underlying mechanisms will aid in developing interventions to decrease the contribution of FGR-born offspring to the global burden of cardiovascular disease. One cause of FGR is maternal undernutrition. In late-gestation undernutrition (LGUN) fetal glucose supply, a main energy source for the fetal heart, is reduced. This may be a key contributor to altered fetal cardiac development; thus restoration of fetal glucose availability in the LGUN setting may be a viable target for intervention. To investigate the role of glucose availability in fetal heart development, we utilized an established pregnant sheep model of LGUN (50% global nutrient restriction) with or without a continuous intrafetal glucose infusion. LGUN reduced fetal plasma glucose concentrations, resulting in brain sparing that was normalized by intrafetal glucose infusion. LGUN decreased the protein abundance of oxidative phosphorylation complexes 1 and 3; however glucose infusion returned complex 3 abundance to that of controls. LGUN increased the phosphorylation of contractility and hypertrophy marker CAMKII, which was associated with increased left ventricular cardiac output; however intrafetal glucose infusion normalized CAMKII. Our findings demonstrate that glucose plays a specific role in regulating cardiac development in utero, highlighting the importance of adequate maternal nutrition in late gestation. KEY POINTS: Maternal late-gestation undernutrition (LGUN) reduces fetal plasma glucose concentrations. To investigate the role of glucose availability in fetal left ventricle (LV) development, we assessed whether LGUN-induced alterations in the contractility, metabolic and hormonal profiles can be ameliorated in LGUN fetuses receiving glucose infusion (LGUN+G). Relative brain weight was increased in LGUN compared to controls and restored in LGUN+G despite fetal glucose infusion only partially normalizing fetal plasma glucose concentrations to that of controls. LGUN decreased cardiac oxidative phosphorylation (OXPHOS)complex 1 and 3 abundance, and LGUN+G restored complex 3 to that of controls. LGUN increased the activation of the contractility marker, Ca²⁺/calmodulin-dependent protein kinase II (p-CAMKII), but restored in LGUN+G. The magnetic resonance imaging measure of the LV cardiac output was positively correlated with p-CAMKII expression in LGUN. This study highlights the role of in utero glucose availability in regulating the abundance of fetal LV OXPHOS complex 3 and CAMKII activation in utero.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175423","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":"Atrial fibrosis in atrial fibrillation: Mechanisms, mapping techniques and clinical applications.","authors":"Caterina Vidal Horrach, Laura Bevis, Cynthia Nwanna, Alexander M Zolotarev, Mahmoud Ehnesh, Semhar Biniam Misghina, Sayed Al-Aidarous, Shohreh Honarbakhsh, Caroline H Roney","doi":"10.1113/JP288680","DOIUrl":"https://doi.org/10.1113/JP288680","url":null,"abstract":"<p><p>Atrial fibrosis plays a pivotal role in the initiation and progression of atrial fibrillation (AF), creating a substrate for AF through structural, electrical and functional remodelling. Atrial remodelling results from various factors, including inflammation, obesity, hypertension and ischaemia, which collectively disrupt cellular coupling and ion channel function. The heterogeneity formed by the distribution of atrial fibrosis creates a substrate for abnormal electrical propagation and arrhythmias through alterations in ionic currents and conduction slowing. The extent of atrial fibrosis may be investigated through multiple modalities, including imaging and electroanatomic mapping. The pathological processes underlying atrial fibrosis are exacerbated in the transition from paroxysmal to persistent AF, highlighting the need for advanced diagnostic and therapeutic strategies. In this review, we cover the role of atrial fibrosis in AF, evaluate the modalities used to quantify and characterize atrial fibrosis, giving an overview of their clinical applications in stratifying patients and guiding treatment strategies, and discuss the integration of fibrosis information in computational AF models. We explore how the combination of experimental and computational techniques can enhance our understanding of the arrhythmogenic effects of fibrosis and the challenges inherent in translating mechanistic insights into effective therapies.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163454","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":"Antioxidant supplementation blunts the proteome response to 3 weeks of sprint interval training preferentially in human type 2 muscle fibres.","authors":"Victoria L Wyckelsma, Marta Murgia, Sigitas Kamandulis, Stefano Gastaldello, Marius Brazaitis, Audrius Snieckus, Nerijus Eimantas, Mati Pääsuke, Sebastian Edman, William Apro, Daniel C Andersson, Håkan Westerblad, Tomas Venckunas","doi":"10.1113/JP288638","DOIUrl":"https://doi.org/10.1113/JP288638","url":null,"abstract":"<p><p>Sprint interval training (SIT) is a time-efficient type of endurance training that involves large type 2 muscle fibre recruitment. Effective antioxidant supplementation may mitigate positive training adaptations by limiting the oxidant challenge. Our aim was to test whether SIT affects type 2 more than type 1 muscle fibres, and whether the muscular training response is mitigated by antioxidant treatment. Young men performed three weekly SIT sessions (4-6 × 30 s all-out cycling) for 3 weeks while treated with antioxidants (vitamin C, 1 g day^-1; vitamin E, 235 mg day^-1) or placebo. Vastus lateralis biopsies were taken to measure (i) activation of genes for reactive oxygen/nitrogen species (ROS) sensors and inflammatory mediators with quantitative RT-PCR and (ii) fibre type-specific proteome adaptations using MS-based proteomics. Vitamin treatment decreased the upregulation of genes for ROS sensors and inflammatory regulators during the first SIT session. The 3 weeks of SIT caused generally larger proteome adaptations in type 2 than in type 1 fibres, and this included larger increases in abundance of proteins involved in mitochondrial energy production. Vitamin treatment blunted the SIT-induced proteome adaptations, whereas it did not affect the training-induced improvement in maximal cycling performance. In conclusion, (i) the large type 2 fibre recruitment and resulting proteome adaptations are instrumental to the effectiveness of SIT and (ii) antioxidant supplementation counteracts positive muscular adaptations to SIT, which would blunt any improvement in submaximal endurance performance, whereas it does not affect the improvement in maximal cycling performance, where O₂ delivery to muscle would be limiting. KEY POINTS: Sprint interval training (SIT) is a time-efficient type of endurance training that involves large recruitment of fast-twitch muscle fibres. Treatment with antioxidants may mitigate the positive effects of endurance training. Fibre type-specific proteomics performed on muscle biopsies obtained from young men before and after 3 weeks of SIT showed larger training effects in fast- than in slow-twitch fibres. Antioxidant treatment in the form of vitamin C and E pills counteracted the positive muscular adaptations to the 3 weeks of SIT. These results increase our understanding of why SIT is an effective endurance training regime and provide further evidence against the common belief that antioxidant supplements are beneficial in a physical exercise context.</p>","PeriodicalId":50088,"journal":{"name":"Journal of Physiology-London","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163428","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}