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Carotid chemoreceptor inhibition improves exercise tolerance in participants with elevated carotid chemosensitivity: A secondary analysis 颈动脉化学受体抑制可改善颈动脉化学敏感性升高参与者的运动耐受性:一项次要分析
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-04-05 DOI: 10.1016/j.autneu.2025.103278
Sophie É. Collins , Devin B. Phillips , Michael K. Stickland

Rationale

Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are characterized by exaggerated carotid chemoreceptor (CC) sensitivity and exercise intolerance. We tested the hypothesis that participants with elevated CC sensitivity would have the greatest improvement in exercise tolerance with CC inhibition, secondary to increased vascular conductance, and lower ventilatory requirements, dyspnea and leg discomfort.

Methods

Data from healthy controls, and patients with CHF or COPD were included in this secondary analysis of results from 2 randomized placebo-controlled double-blind crossover trials. Assessments included pulmonary function, incremental cardiopulmonary exercise test, and basal CC sensitivity assessment. High CC sensitivity was defined as either a stepwise hypoxic ventilatory response (HVR) or transient HVR greater than one SD above the mean in healthy controls. Participants received 2 μg/kg/min dopamine or placebo infusions (randomized) during 2 separate constant work-rate exercise tests to examine exercise endurance time (EET) and cardiopulmonary responses.

Results

Among 33 adults, 17 were categorized to normal HVR (11 controls/3 COPD/3 CHF), and 16 to high HVR (1 control/7 COPD/8 CHF). Participants with high HVR experienced significant dopamine-induced improvements in EET (pinteraction = 0.011), and reduced leg discomfort at the 4-min isotime (pinteraction = 0.024). Those with improved vascular conductance and leg discomfort had the greatest improvements in EET (p = 0.042 and p = 0.021, respectively).

Conclusions

CC inhibition with dopamine in participants with high HVR was associated with improvement in EET. These findings suggest that high HVR is related to exercise limitation, and that improvement in EET is associated with a CC-mediated increase in vascular conductance and leg discomfort.
原理 慢性心力衰竭(CHF)和慢性阻塞性肺病(COPD)的特点是颈动脉化学感受器(CC)敏感性增高和运动耐受性差。我们测试了这样一个假设:CC 敏感性升高的参与者在使用 CC 抑制剂后,运动耐受性会得到最大改善,这是因为血管传导性增加,通气要求降低,呼吸困难和腿部不适减轻。评估包括肺功能、增量心肺运动测试和基础 CC 敏感性评估。高CC敏感性被定义为阶跃性缺氧通气反应(HVR)或瞬时HVR高于健康对照组平均值一个标准差以上。结果 在 33 名成人中,17 人被归类为正常 HVR(11 名对照组/3 名慢性阻塞性肺病患者/3 名慢性阻塞性肺病患者),16 人被归类为高 HVR(1 名对照组/7 名慢性阻塞性肺病患者/8 名慢性阻塞性肺病患者)。高 HVR 参与者在多巴胺的诱导下,EET 显著改善(pinteraction = 0.011),4 分钟等时腿部不适感减轻(pinteraction = 0.024)。结论多巴胺对高 HVR 参与者的多巴胺抑制与 EET 的改善有关。这些研究结果表明,高 HVR 与运动受限有关,而 EET 的改善与 CC 介导的血管传导和腿部不适的增加有关。
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引用次数: 0
The role of cardiopulmonary baroreflex on sympathetic vasomotor outflow and blood pressure regulation during dynamic exercise 动态运动中心肺压力反射在交感血管舒张性流出和血压调节中的作用
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-04-04 DOI: 10.1016/j.autneu.2025.103276
Keisho Katayama , Shigehiko Ogoh
Precise cardiovascular adjustments are necessary to meet the metabolic demands of working skeletal muscle during dynamic exercise. Appropriate regulation of sympathetic vasomotor outflow is key for maintaining arterial blood pressure (ABP) and facilitating the delivery of blood flow to active skeletal muscle. Central command, the exercise pressor reflex (including mechanoreflex and metaboreflex within skeletal muscle), and the arterial baroreflex work in concert, creating complex interactions that regulate sympathetic vasomotor outflow during dynamic exercise. Although less well studied, limited evidence suggests that the cardiopulmonary baroreflex plays a significant role in modulating MSNA (muscle sympathetic nerve activity) and ABP responses during mild-intensity dynamic exercise, as well as in resetting the arterial baroreflex during dynamic exercise. This review provides an updated and comprehensive overview of the sympathetic vasomotor outflow and the ABP response during dynamic exercise via the cardiopulmonary baroreflex.
在动态运动中,精确的心血管调节是满足骨骼肌代谢需求的必要条件。适当调节交感血管舒张性流出是维持动脉血压(ABP)和促进血液流向活跃骨骼肌的关键。中枢指令、运动压力反射(包括骨骼肌内的机械反射和代谢反射)和动脉压力反射协同工作,产生复杂的相互作用,调节动态运动期间交感血管舒张性外流。尽管研究较少,但有限的证据表明,心肺压力反射在轻度动态运动中调节MSNA(肌肉交感神经活动)和ABP反应,以及在动态运动中重置动脉压力反射中发挥重要作用。本文综述了动态运动中通过心肺调压反射的交感血管舒缩性流出和ABP反应的最新和全面概述。
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引用次数: 0
The influence of sleep on autonomic nervous system regulation in women across the lifespan 女性一生中睡眠对自主神经系统调节的影响
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-30 DOI: 10.1016/j.autneu.2025.103275
Jeremy A. Bigalke, Jason R. Carter
Sleep and autonomic regulation are closely related processes which incur significant influence on health and wellbeing in women across the lifespan. Aging in women is associated with increases in cardiovascular risk through greater sympathetic predominance compared to premenopausal women, as well as reductions in sleep quality and quantity. Women remain an understudied population with regards to sleep, autonomic function, and cardiovascular risk. Understanding the interplay between sleep and autonomic function across the lifespan of women is crucial to improve subsequent lifelong health outcomes. The present review integrates knowledge that has accrued regarding experimental sleep deprivation, restriction, and chronic sleep disturbance and their respective impacts on autonomic regulation at various life stages in women. The review focuses on high-fidelity measures of sympathetic regulation (i.e., microneurography), as aging in women is associated with a disproportionate increase in sympathetic activity compared to men. Evidence summarized within this review delineates a significant impact of sleep processes on autonomic function in women across the lifespan. However, there remain substantial gaps in our knowledge of this interplay between sleep processes and autonomic regulation of cardiovascular control in women. There is a need for further research efforts to disentangle the complexity associated with sleep and autonomic regulation in women at all life stages. Efforts in this area will improve our understanding of women's health and factors such as sleep and sleep disturbance which precipitate lifelong health and chronic cardiovascular risk.
睡眠和自主调节是密切相关的过程,在整个生命周期中对女性的健康和福祉产生重大影响。与绝经前女性相比,女性的交感神经优势更大,与心血管风险增加有关,同时睡眠质量和数量也有所减少。女性在睡眠、自主神经功能和心血管风险方面的研究仍然不足。了解女性一生中睡眠和自主神经功能之间的相互作用,对于改善随后的终身健康状况至关重要。本综述整合了有关实验性睡眠剥夺、限制和慢性睡眠障碍及其各自对女性不同生命阶段自主调节的影响的知识。该综述侧重于交感调节的高保真测量(即微神经摄影),因为与男性相比,女性的衰老与交感活动的不成比例的增加有关。本综述总结的证据描述了女性一生中睡眠过程对自主神经功能的重大影响。然而,我们对女性睡眠过程和心血管控制的自主调节之间的相互作用的了解仍然存在很大的差距。有必要进行进一步的研究,以解开女性在各个生命阶段与睡眠和自主调节相关的复杂性。在这一领域的努力将提高我们对妇女健康和诸如睡眠和睡眠障碍等因素的理解,这些因素会导致终身健康和慢性心血管风险。
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引用次数: 0
Autonomic control of blood pressure in women: The roles of hypertension and aging 女性血压的自主控制:高血压和衰老的作用
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-29 DOI: 10.1016/j.autneu.2025.103274
John D. Akins, Takuro Washio, Qi Fu
Hypertension remains a leading cause of cardiovascular morbidity and mortality worldwide, with implications in women's health across the lifespan. Of note, autonomic nervous system imbalances have been linked to the development of hypertension and are present with natural aging and various conditions unique to women (e.g., menopause, hypertensive disorders of pregnancy, polycystic ovary syndrome). As such, this article reviews the critical changes in the sympathetic and parasympathetic nervous systems that occur in women and may contribute to the development of hypertension. Special focus is paid to the regulating pathways across the baroreflex arc, including baroreflex sensitivity, efferent sympathetic outflow, and peripheral sympathetic transduction, at rest and during various physiological stressors. To this point, aging women experience increasing sympathetic outflow, blunted sympathetic transduction, and reduced cardiovagal baroreflex sensitivity, which may be further potentiated by the presence of hypertension. Additionally, this review applies some clinical perspective to the physiological findings in order to identify potential therapeutic pathways. The information gathered in this review has important implications for future research into women's autonomic blood pressure regulation and its impact on the genesis of hypertension.
高血压仍然是全世界心血管疾病发病率和死亡率的主要原因,对妇女一生的健康都有影响。值得注意的是,自主神经系统失衡与高血压的发展有关,并与自然衰老和女性特有的各种疾病(如更年期、妊娠期高血压疾病、多囊卵巢综合征)有关。因此,本文回顾了女性交感和副交感神经系统的关键变化,这些变化可能有助于高血压的发展。特别关注的是在静息和各种生理应激时,横跨压力反射弧的调节途径,包括压力反射敏感性、输出交感神经输出和外周交感神经转导。到目前为止,老年妇女交感神经外流增加,交感神经传导减弱,心血管压力反射敏感性降低,这可能因高血压的存在而进一步增强。此外,本综述将一些临床观点应用于生理学发现,以确定潜在的治疗途径。本综述收集的信息对未来研究女性自主血压调节及其对高血压发生的影响具有重要意义。
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引用次数: 0
The effects of rhythmic handgrip exercise on muscle sympathetic nerve activity: A systematic review and meta-analysis 有节奏的握力运动对肌肉交感神经活动的影响:系统回顾和荟萃分析
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-26 DOI: 10.1016/j.autneu.2025.103272
Lauren E. Maier , Sarah E. Meyer , Andy Deprato , Stephen Busch , Allison Sivak , Margie H. Davenport , Craig D. Steinback
This systematic review and meta-analysis was conducted to quantify the sympathetic response to rhythmic handgrip exercise in healthy and diseased populations. Structured searches of databases were performed until June 12, 2024. We included all primary studies (other than systematic reviews and meta-analyses), and inclusion criteria were: population (all populations); intervention (rhythmic handgrip); comparator (baseline); and outcome (MSNA, BP, HR). Forty-nine studies (n = 930) were included. Burst frequency was elevated by 6.1 bursts/min during rhythmic handgrip (95 % CI, 4.52, 7.63; I2 = 53 %; p < 0.00001) across all populations. Similarly, burst incidence and total activity showed significant increases during handgrip (BI: MD, 3.0 bursts/100 hbs; 95 % CI, 0.11, 5.85; I2 = 0 %; p = 0.04; TA: MD, 49.4 a.u.; 95 % CI, 36.56, 62.20; I2 = 86 %; p < 0.00001). Subgroup analyses found greater responses in MSNA during rhythmic handgrip in healthy individuals compared to cardiovascular diseases and other conditions. Specifically, the change in burst frequency during handgrip (p = 0.0009) and total activity during handgrip (p < 0.00001) suggest a blunted sympathetic response to rhythmic handgrip in diseased populations. Meta-regression analyses in healthy populations found no relationship between the volume of handgrip applied with the associated change in sympathetic activity; however, there was a significant positive relationship between both the change in heart rate (slope = 0.131; adjusted R2 = 0.2773; p = 0.002) and the change in mean blood pressure (slope = 0.163; adjusted R2 = 0.3594; p < 0.001) with handgrip volume. An increase in MSNA is observed during rhythmic handgrip despite ranging protocols, populations, and co-interventions. These results suggest exercise is a unique stressor and challenges the understanding of general sympathetic hyperactivity in diseased populations.
本系统综述和荟萃分析旨在量化健康和患病人群对有节奏握力运动的交感神经反应。数据库的结构化搜索一直持续到2024年6月12日。我们纳入了所有的初步研究(除了系统评价和荟萃分析),纳入标准为:人群(所有人群);干预(有节奏的握法);比较器(基线);结果(MSNA、BP、HR)。纳入49项研究(n = 930)。节律握力时爆发频率增加6.1次/min (95% CI, 4.52, 7.63;i2 = 53%;p & lt;0.00001)。同样,握力时爆发发生率和总活动显著增加(BI: MD, 3.0次爆发/100 hbs;95% ci, 0.11, 5.85;i2 = 0%;p = 0.04;TA:医学博士,49.4 a.u.;95% ci, 36.56, 62.20;i2 = 86%;p & lt;0.00001)。亚组分析发现,与心血管疾病和其他疾病相比,健康个体在节律性握力过程中MSNA的反应更大。具体来说,握拳期间突发频率的变化(p = 0.0009)和握拳期间总活动(p <;0.00001)表明在患病人群中对有节奏的握力的交感神经反应迟钝。健康人群的meta回归分析发现,握力的量与交感神经活动的相关变化之间没有关系;然而,两者之间存在显著的正相关关系(斜率= 0.131;调整后R2 = 0.2773;P = 0.002)和平均血压变化(斜率= 0.163;调整后R2 = 0.3594;p & lt;0.001)与握把量有关。尽管有不同的方案、人群和联合干预,但在有节奏的握拍过程中观察到MSNA的增加。这些结果表明,运动是一种独特的压力源,挑战了对患病人群普遍交感神经过度活跃的理解。
{"title":"The effects of rhythmic handgrip exercise on muscle sympathetic nerve activity: A systematic review and meta-analysis","authors":"Lauren E. Maier ,&nbsp;Sarah E. Meyer ,&nbsp;Andy Deprato ,&nbsp;Stephen Busch ,&nbsp;Allison Sivak ,&nbsp;Margie H. Davenport ,&nbsp;Craig D. Steinback","doi":"10.1016/j.autneu.2025.103272","DOIUrl":"10.1016/j.autneu.2025.103272","url":null,"abstract":"<div><div>This systematic review and meta-analysis was conducted to quantify the sympathetic response to rhythmic handgrip exercise in healthy and diseased populations. Structured searches of databases were performed until June 12, 2024. We included all primary studies (other than systematic reviews and meta-analyses), and inclusion criteria were: population (all populations); intervention (rhythmic handgrip); comparator (baseline); and outcome (MSNA, BP, HR). Forty-nine studies (n = 930) were included. Burst frequency was elevated by 6.1 bursts/min during rhythmic handgrip (95 % CI, 4.52, 7.63; I<sup>2</sup> = 53 %; p &lt; 0.00001) across all populations. Similarly, burst incidence and total activity showed significant increases during handgrip (BI: MD, 3.0 bursts/100 hbs; 95 % CI, 0.11, 5.85; I<sup>2</sup> = 0 %; p = 0.04; TA: MD, 49.4 a.u.; 95 % CI, 36.56, 62.20; I<sup>2</sup> = 86 %; p &lt; 0.00001). Subgroup analyses found greater responses in MSNA during rhythmic handgrip in healthy individuals compared to cardiovascular diseases and other conditions. Specifically, the change in burst frequency during handgrip (p = 0.0009) and total activity during handgrip (p &lt; 0.00001) suggest a blunted sympathetic response to rhythmic handgrip in diseased populations. Meta-regression analyses in healthy populations found no relationship between the volume of handgrip applied with the associated change in sympathetic activity; however, there was a significant positive relationship between both the change in heart rate (slope = 0.131; adjusted R<sup>2</sup> = 0.2773; p = 0.002) and the change in mean blood pressure (slope = 0.163; adjusted R<sup>2</sup> = 0.3594; p &lt; 0.001) with handgrip volume. An increase in MSNA is observed during rhythmic handgrip despite ranging protocols, populations, and co-interventions. These results suggest exercise is a unique stressor and challenges the understanding of general sympathetic hyperactivity in diseased populations.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"259 ","pages":"Article 103272"},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791926","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}
引用次数: 0
Orthostatic cardiovascular responses to postural sway and discreet counterpressure maneuvers 直立心血管对姿势摇摆和谨慎的反压动作的反应
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-25 DOI: 10.1016/j.autneu.2025.103271
E.L. Williams , J. Lando , V.-E.M. Lucci , B.C.D. Hockin , K. Elabd , S.N. Robinovitch , I.T. Parsons , V.E. Claydon
Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingly, we aimed to evaluate a series of discreet, accessible movements as novel preventative CPM.
We tested 26 healthy adults (12 female) aged 28.9 ± 1.2 years. Participants performed a baseline stand (BL), followed by three randomized CPM trials (exaggerated anteroposterior sway, AP; toe clenching, TC; gluteal muscle clenching, GC). Non-invasive beat-to-beat systolic arterial pressure (SAP), heart rate, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), mean middle cerebral artery blood velocity (mMCAv), and total path length moved (TPL) were measured. Muscularity was assessed using bioelectrical impedance.
All discreet CPM augmented orthostatic SV (p < 0.001) and CO (p < 0.001), while reducing TPR (p < 0.001). SAP increased during AP (p < 0.001) and GC (p < 0.001), but not TC. GC responses were unstable, with increased standard deviation of SAP (p = 0.002) and SV (p = 0.022) that may predispose syncope. Only AP improved mMCAv (p = 0.005) and sympathovagal balance (p < 0.001). Responses were largest in those with greater initial cardiovascular instability (p < 0.003), larger leg muscle mass (p < 0.02), and where TPL was greater (p < 0.002).
These novel CPM hold clinical potential for the prevention of orthostatic syncope and presyncope, while addressing real-world patient-reported barriers to CPM. Exaggerated AP sway was most robust and stable at improving orthostatic hemodynamics in healthy controls, with reduced reliance on sympathetic baroreflex-mediated vasoconstriction during enhanced muscle pumping activity. Accordingly, AP shows the most promise as a simple and discrete CPM.
反压动作(CPM)是用来延缓或中止晕厥的动作,但可能有实际的障碍。我们最近发现过度的姿势摇摆可以产生防止晕厥的保护性反应。因此,我们的目标是评估一系列谨慎的、可接近的运动作为新的预防性CPM。健康成人26例,其中女性12例,年龄28.9±1.2岁。参与者进行了基线站立(BL),随后进行了三个随机CPM试验(夸张的前后摇摆,AP;脚趾握紧,TC;臀肌握紧(GC)。测量无创搏动收缩压(SAP)、心率、每搏量(SV)、心输出量(CO)、总外周阻力(TPR)、平均大脑中动脉血流速度(mMCAv)和总路径移动长度(TPL)。采用生物电阻抗法评估肌肉强度。全离散CPM增强直立SV (p <;0.001)和CO (p <;0.001),同时降低TPR (p <;0.001)。AP期间SAP升高(p <;0.001)和GC (p <;0.001),但不是TC。GC反应不稳定,SAP (p = 0.002)和SV (p = 0.022)的标准差增加可能导致晕厥。只有AP能改善mMCAv (p = 0.005)和交感迷走神经平衡(p <;0.001)。在初始心血管不稳定程度较高的患者中反应最大(p <;0.003),腿部肌肉质量较大(p <;0.02), TPL更大(p <;0.002)。这些新型CPM具有预防直立性晕厥和晕厥前期的临床潜力,同时解决了现实世界中患者报告的CPM障碍。在健康对照中,过度的AP摆动在改善直立血流动力学方面是最稳健和稳定的,在增强的肌肉泵送活动中,对交感压力反射介导的血管收缩的依赖减少。因此,AP作为一种简单而离散的CPM显示出最大的前景。
{"title":"Orthostatic cardiovascular responses to postural sway and discreet counterpressure maneuvers","authors":"E.L. Williams ,&nbsp;J. Lando ,&nbsp;V.-E.M. Lucci ,&nbsp;B.C.D. Hockin ,&nbsp;K. Elabd ,&nbsp;S.N. Robinovitch ,&nbsp;I.T. Parsons ,&nbsp;V.E. Claydon","doi":"10.1016/j.autneu.2025.103271","DOIUrl":"10.1016/j.autneu.2025.103271","url":null,"abstract":"<div><div>Counterpressure maneuvers (CPM) are movements used to delay or abort syncope, but may have practical barriers to use. We recently showed exaggerated postural sway produces protective responses against syncope. Accordingly, we aimed to evaluate a series of discreet, accessible movements as novel preventative CPM.</div><div>We tested 26 healthy adults (12 female) aged 28.9 ± 1.2 years. Participants performed a baseline stand (BL), followed by three randomized CPM trials (exaggerated anteroposterior sway, AP; toe clenching, TC; gluteal muscle clenching, GC). Non-invasive beat-to-beat systolic arterial pressure (SAP), heart rate, stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), mean middle cerebral artery blood velocity (mMCAv), and total path length moved (TPL) were measured. Muscularity was assessed using bioelectrical impedance.</div><div>All discreet CPM augmented orthostatic SV (<em>p</em> &lt; 0.001) and CO (<em>p</em> &lt; 0.001), while reducing TPR (<em>p</em> &lt; 0.001). SAP increased during AP (<em>p</em> &lt; 0.001) and GC (<em>p</em> &lt; 0.001), but not TC. GC responses were unstable, with increased standard deviation of SAP (<em>p</em> = 0.002) and SV (<em>p</em> = 0.022) that may predispose syncope. Only AP improved mMCAv (<em>p</em> = 0.005) and sympathovagal balance (<em>p</em> &lt; 0.001). Responses were largest in those with greater initial cardiovascular instability (<em>p</em> &lt; 0.003), larger leg muscle mass (<em>p</em> &lt; 0.02), and where TPL was greater (<em>p</em> &lt; 0.002).</div><div>These novel CPM hold clinical potential for the prevention of orthostatic syncope and presyncope, while addressing real-world patient-reported barriers to CPM. Exaggerated AP sway was most robust and stable at improving orthostatic hemodynamics in healthy controls, with reduced reliance on sympathetic baroreflex-mediated vasoconstriction during enhanced muscle pumping activity. Accordingly, AP shows the most promise as a simple and discrete CPM.</div></div>","PeriodicalId":55410,"journal":{"name":"Autonomic Neuroscience-Basic & Clinical","volume":"260 ","pages":"Article 103271"},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143777539","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}
引用次数: 0
Colonic mucosal TRPA1 expression profiles in irritable bowel syndrome and its correlation to symptom severity: An exploratory study 肠易激综合征结肠黏膜TRPA1表达谱及其与症状严重程度的相关性:一项探索性研究
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-25 DOI: 10.1016/j.autneu.2025.103273
Sylvester R. Groen , Daniel Keszthelyi , Ellen Wilms , Justin Huig , Pan Xu , Montserrat Elizalde , Lisa Vork , Daisy M.A.E. Jonkers , Zsuzsanna Helyes , Ad A.M. Masclee , Zsa Zsa R.M. Weerts

Introduction

Visceral hypersensitivity is a hallmark of irritable bowel syndrome (IBS). A putative involvement of the Transient Receptor Potential Ankyrin-1 (TRPA1) cation channel has been suggested by several animal studies. Main objective of this study is to assess location-specific TRPA1 expression in the colonic mucosa and its correlation with symptom severity in IBS patients.

Methods

Biopsies were obtained from the sigmoid of 30 IBS patients (Rome III; median age 39.0 years, 80 % female) and 23 healthy controls (median age 22.7 years, 43.5 % female). Additional biopsies of the proximal colon were obtained in 24 IBS patients. TRPA1 expression levels were measured in duplicate by quantitative reverse-transcriptase–polymerase-chain-reaction, normalized to GAPDH, and assessed as relative mRNA values using the −2ΔCt method. In IBS patients, symptoms were assessed and correlated with TRPA1 expression.

Results

Relative TRPA1 expression in the sigmoid was significantly higher in IBS patients compared to healthy controls (P < 0.001). Within IBS patients TRPA1 expression of sigmoid biopsies was significantly higher compared to proximal colon samples (p < 0.001). No significant correlation was found between TRPA1 expression in sigmoid or proximal colon samples and the symptom severity (abdominal discomfort, abdominal pain and bloating).

Conclusion

These findings suggest a potential role for the TRPA1 related pathway as a target for IBS treatment in the future. Since there was no correlation found in the current exploratory study between TRPA1 expression and symptom severity, further research towards the clinical relevance of the increased TRPA1 expression in IBS-patients along with its location-specific expression is warranted.
内脏过敏是肠易激综合征(IBS)的一个标志。一些动物研究表明,瞬时受体电位锚蛋白-1 (TRPA1)阳离子通道可能参与其中。本研究的主要目的是评估肠易激综合征患者结肠黏膜中TRPA1的位置特异性表达及其与症状严重程度的相关性。方法对30例IBS患者进行乙状结肠活检(Rome III;中位年龄39.0岁,80%为女性)和23名健康对照(中位年龄22.7岁,43.5%为女性)。对24例IBS患者进行了近端结肠活检。通过定量逆转录-聚合酶链反应检测TRPA1的表达水平,归一化为GAPDH,并使用−2ΔCt方法评估相对mRNA值。在IBS患者中,评估症状并与TRPA1表达相关。结果IBS患者乙状结肠中TRPA1的相对表达明显高于健康对照组(P <;0.001)。在IBS患者中,乙状结肠活检组织中TRPA1的表达明显高于近端结肠样本(p <;0.001)。在乙状结肠或近端结肠样本中TRPA1表达与症状严重程度(腹部不适、腹痛和腹胀)无显著相关性。结论这些发现提示TRPA1相关通路在未来作为IBS治疗靶点的潜在作用。由于目前的探索性研究未发现TRPA1表达与症状严重程度之间的相关性,因此需要进一步研究TRPA1在ibs患者中表达升高及其部位特异性表达的临床相关性。
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引用次数: 0
Cardiovascular and sympathetic neural responses during acute vagus nerve stimulation and subsequent static handgrip exercise in healthy adults 急性迷走神经刺激和随后的静态握力运动对健康成人的心血管和交感神经反应
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-25 DOI: 10.1016/j.autneu.2025.103270
Takuro Washio , John D. Akins , Sarah L. Hissen , Anna K. Geib , Skyler A. Robles , Qi Fu

Purpose

This study aimed to investigate cardiovascular and sympathetic neural responses during acute cervical non-invasive vagus nerve stimulation (nVNS) and subsequent static handgrip (SHG) exercise with post-exercise circulatory occlusion (PECO) in healthy humans.

Methods

Ten healthy adults (5 men and 5 women, 33 ± 9 [standard deviation] yrs) participated in this double-blinded, randomized, crossover study. Each participant was studied twice on two separate days, with approximately 4 weeks apart: once during the actual cervical nVNS and once during sham stimulation for 4 min each. Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA) were measured during nVNS and sham stimulation. In addition, participants performed SHG at 40 % of maximal voluntary contraction until fatigue, followed by 2-min PECO to isolate muscle metaboreflex activation before and after each stimulation.

Results

During both nVNS and sham stimulation, HR decreased (△−4 ± 4 and △−4 ± 5 bpm; both P < 0.001), and MSNA increased (△4 ± 6 and △2 ± 3 bursts/min; both P < 0.001) in all participants, although MAP remained unchanged (P = 0.312). However, these responses did not differ between nVNS and sham stimulation (all P > 0.05). Additionally, there were no differences in cardiovascular and MSNA responses to fatiguing SHG and PECO between stimulations (all P > 0.05).

Conclusion

Compared to the sham condition, cervical nVNS had no significant impact on cardiovascular variables and MSNA during acute stimulation, nor on the responses to SHG or PECO. These findings suggest that cervical nVNS has no or minimal acute effect on sympathetic neural (re)activity in healthy adults.
目的本研究旨在探讨急性颈部无创迷走神经刺激(nVNS)和随后的静止握力(SHG)运动伴运动后循环闭塞(PECO)时的心血管和交感神经反应。方法10名健康成人(男5名,女5名,33±9[标准差]岁)参加了这项双盲、随机、交叉研究。每个参与者分别在两天进行两次研究,间隔约4周:一次在实际的颈椎nVNS期间,一次在假刺激期间,每次4分钟。在nVNS和假刺激期间测量平均动脉压(MAP)、心率(HR)和肌肉交感神经活动(MSNA)。此外,参与者以最大自愿收缩的40%进行SHG,直到疲劳,然后在每次刺激前后进行2分钟的PECO,以隔离肌肉代谢反射激活。结果nVNS和假性刺激时,心率降低(△−4±4和△−4±5 bpm);P <;0.001), MSNA增加(△4±6次和△2±3次/min;P <;0.001),尽管MAP保持不变(P = 0.312)。然而,这些反应在nVNS和假刺激之间没有差异(所有P >;0.05)。此外,两种刺激对疲劳SHG和PECO的心血管和MSNA反应没有差异(所有P >;0.05)。结论与假手术相比,颈椎nVNS对急性刺激时的心血管变量和MSNA无显著影响,对SHG和PECO的反应无显著影响。这些发现表明,颈椎nVNS对健康成人交感神经(re)活动没有或只有很小的急性影响。
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引用次数: 0
Dissecting the exercise pressor reflex in heart failure: A multi-step failure 剖析心力衰竭的运动加压反射:多步骤失败。
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-13 DOI: 10.1016/j.autneu.2025.103269
Danilo Iannetta , Fabio Giuseppe Laginestra , D. Walter Wray , Markus Amann
The contribution of neural feedback originating from exercising limb muscles to the cardiovascular response to exercise was first recognized nearly 100 years ago. Today, it is well established that this influence is initiated by the activation of group III and IV sensory neurons with terminal endings located within contracting skeletal muscle. During exercise, these sensory neurons project feedback related to intramuscular mechanical and metabolic perturbations to medullary neural circuits which reflexively evoke decreases in parasympathetic and increases in sympathetic nervous system activity with the purpose of optimizing central and peripheral hemodynamics. Considerable evidence from animal and human studies suggests that the function of this regulatory control system, known as the exercise pressor reflex (EPR), is abnormal in heart failure and exaggerates sympatho-excitation which impairs the hemodynamic response to exercise and contributes to the functional limitations characterizing these patients. This review briefly introduces the key determinants of EPR control in health and covers the impact of heart failure on the integrity of each of its components and overall function. These include the sensitivity of group III/IV muscle afferents, afferent signal transmission in the spinal cord, and the central integration and processing of sensory feedback within the brainstem. Importantly, although most data relevant for this review come from studies in HFrEF, the limited HFpEF-specific insights are included when available. While arguably not part of the EPR, we also discuss the impact of heart failure on the exercise-induced increase of intramuscular stimuli of group III/IV muscle afferents and end-organ responsiveness to sympathetic/neurochemical stimulation.
源自肢体肌肉运动的神经反馈对心血管运动反应的贡献在近100年前首次被认识到。今天,已经确定这种影响是由末端位于收缩骨骼肌内的III和IV组感觉神经元的激活引起的。在运动过程中,这些感觉神经元将与肌内机械和代谢扰动相关的反馈投射到延髓神经回路,从而反射性地引起副交感神经系统活动的减少和交感神经系统活动的增加,以优化中枢和外周血流动力学。来自动物和人体研究的大量证据表明,这种被称为运动加压反射(EPR)的调节控制系统的功能在心力衰竭中是异常的,它会夸大交感神经兴奋,从而损害对运动的血液动力学反应,并导致这些患者的功能限制。本文简要介绍了健康中EPR控制的关键决定因素,并涵盖了心力衰竭对其每个组成部分的完整性和整体功能的影响。这些包括III/IV组肌肉传入神经的敏感性,脊髓传入信号的传递,以及脑干内感觉反馈的中枢整合和处理。重要的是,尽管与本综述相关的大多数数据来自HFrEF研究,但有限的hfpef特异性见解也包括在内。虽然可以说不是EPR的一部分,但我们也讨论了心力衰竭对运动诱导的III/IV组肌肉传入刺激增加和终末器官对交感/神经化学刺激的反应的影响。
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引用次数: 0
Renal nerve afferents drive preferential renal sympathoexcitation in response to acute renal ischemia/reperfusion in rats 大鼠急性肾缺血/再灌注时肾神经传入驱动优先的肾交感神经兴奋
IF 3.2 4区 医学 Q2 NEUROSCIENCES Pub Date : 2025-03-12 DOI: 10.1016/j.autneu.2025.103268
A.C. Marreiros , M.I.O. Milanez , R.S. Carvalhal , E.E. Nishi , D.D. Santos , C.D. Gil , R. Lantyer , M.M. Knuepfer , C.T. Bergamaschi , R.R. Campos
Renal nerve activity is composed of afferent (sensory) and efferent (sympathetic) nerve activity. Ischemia/reperfusion (IR) of the kidney increases renal sympathetic nerve activity (rSNA) and depresses renal function. As the role of renal afferent fibers in acute renal IR is unclear, we tested the hypothesis that renal IR increases rSNA triggered by renal afferent nerves responding to acute ischemia. Two experimental series were performed in adult male Wistar rats. IR was induced by total obstruction of blood flow to the left kidney by clamping the renal artery for 60 min and reperfusion for 120 min. We recorded MAP, HR, rSNA, and splanchnic sympathetic vasomotor activity (sSNA) in 8 normal IR rats and 6 left kidney deafferented IR rats (IR ARD). Renal deafferentation was performed using capsaicin administration to the left renal nerve 2 weeks before the experiments. Blood samples were collected before ischemia and at the end of reperfusion for total and differential leukocyte counts. Renal ischemia significantly increased rSNA 23 % (20 min: 0,07 ± 0,04mVs P < 0.05) but not sSNA. The increase in rSNA was triggered by activation of renal afferent fibers, since IR significantly reduced rSNA in the IR ARD group maximal decrease in frequency 22 % (180 min: −62 ± 29Δspikes/s) and in amplitude 41 % (−0,29 ± 0, 12mVs, P < 0.05) and induced hypotension and bradycardia. However, no significant difference was observed between groups in blood leukocyte profile, but a significant reduction in renal IL-6 was found in IR ARD, suggesting a reduction in renal inflammation in deafferented IR rats. The results show that renal afferent nerves trigger a preferential increase in rSNA and inflammation in the kidney during acute IR.
肾脏神经活动由传入(感觉)和传出(交感)神经活动组成。肾脏缺血/再灌注(IR)会增加肾交感神经活动(rSNA)并抑制肾功能。由于肾传入纤维在急性肾脏 IR 中的作用尚不清楚,我们测试了肾脏 IR 会增加肾传入神经对急性缺血的反应所引发的 rSNA 的假设。我们对成年雄性 Wistar 大鼠进行了两个系列的实验。通过夹闭肾动脉完全阻断左肾血流 60 分钟和再灌注 120 分钟诱导肾红外。我们记录了 8 只正常 IR 大鼠和 6 只左肾失代偿 IR 大鼠(IR ARD)的 MAP、HR、rSNA 和脾交感血管运动活动(sSNA)。实验前 2 周,通过对左肾神经注射辣椒素进行肾脏去神经支配。在缺血前和再灌注结束时采集血液样本,以检测白细胞总数和差值。肾缺血会使 rSNA 明显增加 23 %(20 分钟:0,07 ± 0,04mVs P < 0.05),但不会使 sSNA 增加。rSNA的增加是由肾传入纤维的激活引发的,因为IR明显降低了IR ARD组的rSNA,最大频率降低了22%(180分钟:-62 ± 29Δ尖峰/秒),振幅降低了41%(-0,29 ± 0, 12mVs,P < 0.05),并诱发了低血压和心动过缓。然而,各组间血液白细胞谱无明显差异,但在 IR ARD 中发现肾 IL-6 显著减少,这表明去干扰 IR 大鼠的肾脏炎症减少。结果表明,肾传入神经在急性 IR 期间会引发 rSNA 和肾脏炎症的优先增加。
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Autonomic Neuroscience-Basic & Clinical
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