Respiratory Physiology & Neurobiology最新文献

Deep inspirations prior to oscillometry for detecting lung alterations in a mouse model of asthma: Yea or nay? 在哮喘小鼠模型中，振荡法检测肺部变化前的深度启发：是还是不是？

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-05-01 Epub Date: 2026-02-13 DOI: 10.1016/j.resp.2026.104551

Andrés Rojas-Ruiz, Jules Hugo Fournier, Cyndi Henry, Ynuk Bossé

Deep inspirations are avoided prior to oscillometry in humans because they transiently improve respiratory mechanics and thereby mask abnormalities in patients with lung diseases. In mice, oscillometry is measured under anesthesia and deep inspirations are contrastingly recommended since they optimize mechanical ventilation and reduce intersubject variability by recruiting closed airways. However, while modeling asthma, a lung disorder burdened by airway closure, deep inspirations may be counterproductive and mitigate differences between mice with and without experimental asthma. Herein, the effect of deep inspirations on respiratory mechanics was quantified in mice with and without experimental asthma. Male BALB/c and C57BL/6 mice were exposed once-daily to either saline or house-dust mite for 10 consecutive days. The day after the last exposure, respiratory mechanics were measured by oscillometry before and after two deep inspirations. In addition to decrease intersubject variability, deep inspirations improved respiratory mechanics in both mouse strains to a magnitude related to the initial level of impairment. Whether deep inspirations mask the detection of alterations caused by experimental asthma depended on the mouse strain. In fact, this question became irrelevant in BALB/c mice when it was discovered that all oscillometric readouts are unchanged by experimental asthma in this mouse strain. In C57BL/6 mice though, the worsening of respiratory mechanics caused by experimental asthma was largely abolished by deep inspirations. Deep inspirations are thus recommended in BALB/c mice since they reduce intersubject variability. However, their utility in C57BL/6 mice is debatable, since the reduced variability may be outweighed by a decreased effect size.

在人类进行振荡测量之前，应避免深吸气，因为深吸气可以短暂地改善呼吸力学，从而掩盖肺部疾病患者的异常。在小鼠中，振荡测量法是在麻醉下测量的，而深吸气则相反地被推荐，因为深吸气可以优化机械通气，并通过招募封闭气道减少受试者间的变异性。然而，在模拟哮喘（一种由气道关闭引起的肺部疾病）时，深度吸气可能适得其反，并减轻了患有和未患有实验性哮喘的小鼠之间的差异。在此，我们量化了深吸气对实验性哮喘和非实验性哮喘小鼠呼吸力学的影响。雄性BALB/c和C57BL/6小鼠每天1次暴露于生理盐水或屋尘螨，连续10天。最后一次暴露的第二天，用振荡法测量两次深吸气前后的呼吸力学。除了减少受试者间的可变性外，深吸气还将两种小鼠的呼吸力学改善到与初始损伤水平相关的程度。深吸气是否掩盖了由实验性哮喘引起的变化的检测取决于小鼠品系。事实上，这个问题在BALB/c小鼠中变得无关紧要，因为发现所有的振荡读数在实验哮喘小鼠中都没有改变。而在C57BL/6小鼠中，深吸气可基本消除实验性哮喘引起的呼吸力学恶化。因此，建议在BALB/c小鼠中进行深度启发，因为它们减少了受试者间的可变性。然而，它们在C57BL/6小鼠中的效用是有争议的，因为减少的变异性可能被减少的效应大小所抵消。

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引用次数: 0

Hypoxia-inducible factor mediates tissue-specific mitochondrial responses to acute hypoxia in mice but not in rats 缺氧诱导因子介导小鼠对急性缺氧的组织特异性线粒体反应，但在大鼠中没有。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-02-06 DOI: 10.1016/j.resp.2026.104549

Maud Demarest, Vincent Joseph

Oxygen availability is a key determinant of cellular homeostasis, and the mitochondrial response to hypoxia is essential for maintaining energy balance and limiting oxidative stress. The hypoxia-inducible factor (HIF) orchestrates transcriptional programs that adjust mitochondrial function by reducing respiration and electron transport to limit reactive oxygen species (ROS) production. We previously reported that mice exhibit greater tolerance to hypoxia than rats, showing HIF-1 stabilization associated with decrease metabolic response under acute hypoxia, and a mitochondrial shift from complex I– to complex II–supported respiration in the brain at high altitude. Here, we investigated the role of HIF in regulating mitochondrial oxygen consumption rates (OCR) in the cerebral cortex and liver of mice and rats exposed to acute hypoxia (10 % O₂, 6 h). To determine whether these effects were HIF-dependent, a group of animals were also treated with deferoxamine (a HIF stabilizer) under normoxia or with 2-methoxyestradiol (a HIF inhibitor) under hypoxia. We demonstrated that acute hypoxia significantly decreases OCR in the liver of mice, an effect that was partially reproduced by HIF stabilization and partly prevented by HIF inhibition, indicating a HIF-dependent mitochondrial response. In contrast, OCR remained unchanged in the cerebral cortex of mice and in both tissues of rats, indicating species- and tissue-specific regulation. These findings reveal that HIF activation under acute hypoxia selectively modulates liver mitochondrial function in mice but not in rats, supporting the view that interspecific differences in HIF-mediated metabolic regulation contribute to the superior hypoxic tolerance of mice.

氧气可用性是细胞稳态的关键决定因素，线粒体对缺氧的反应对于维持能量平衡和限制氧化应激至关重要。缺氧诱导因子（HIF）协调转录程序，通过减少呼吸和电子传递来调节线粒体功能，以限制活性氧（ROS）的产生。我们之前报道过，小鼠比大鼠表现出更强的缺氧耐受性，显示HIF-1稳定与急性缺氧下代谢反应降低有关，并且在高海拔地区大脑中线粒体从复合体I向复合体ii支持的呼吸转变。在这里，我们研究了HIF在急性缺氧（10% O₂，6h）小鼠和大鼠大脑皮层和肝脏线粒体耗氧量（OCR）调节中的作用。为了确定这些影响是否依赖于HIF，一组动物也在缺氧条件下接受去铁胺（一种HIF稳定剂）或2-甲氧基雌二醇（一种HIF抑制剂）治疗。我们证明，急性缺氧显著降低小鼠肝脏的OCR，这一效应部分由HIF稳定再现，部分由HIF抑制阻止，表明HIF依赖性线粒体反应。相比之下，OCR在小鼠的大脑皮层和大鼠的两个组织中保持不变，表明物种和组织特异性调节。这些发现表明，急性缺氧条件下HIF激活选择性地调节小鼠肝脏线粒体功能，但在大鼠中没有，支持了HIF介导的代谢调节的种间差异有助于小鼠卓越的缺氧耐受性的观点。

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引用次数: 0

Strain-specific metabolomic and inflammatory profiles in guinea pigs after LPS-induced inflammation: Comparative analysis of Dunkin-Hartley and Trik strains 豚鼠lps诱导炎症后的菌株特异性代谢组学和炎症谱：Dunkin-Hartley和Trik菌株的比较分析。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-01-28 DOI: 10.1016/j.resp.2026.104547

Juliana Hanusrichterova , Eva Baranovicova , Romana Barosova , Maros Kolomaznik , Pavol Mikolka , Petra Kosutova , Daniela Mokra , Juraj Mokry , Andrea Calkovska

Acute inflammation is a complex biological response triggered by various invading agents provoking distinct immune pathways. As inter-strain variability in guinea pigs can influence inflammatory responses, ultimately affecting disease progression, understanding these strain-specific differences can improve the reliability and translational relevance of guinea pig models for studying acute inflammation. In this study, two guinea pig strains, Trik coloured and Dunkin-Hartley albino, were subjected to bacterial endotoxin lipopolysaccharide (LPS) to induce acute systemic inflammation. Specific metabolite alterations in the blood plasma and bronchoalveolar lavage fluid (BALF) were identified using hydrogen-1 nuclear magnetic resonance (¹H NMR) spectroscopy. Distinct differences in the metabolomic profiles in the blood plasma indicated significant inter-strain variability in circulating metabolites during LPS-induced acute inflammation, including those involved in amino acid transamination, ammonia transfer, and immune responses. Metabolomic analysis of BALF from guinea pigs with LPS-induced inflammation revealed decreased levels of specific metabolites. Moreover, changes in blood and BALF white blood cell counts and body weight were evaluated after LPS exposure. In BALF, LPS caused a slight, non-significant increase in total cell count and a significant neutrophil increase in the Dunkin-Hartley strain. In blood, Trik strain showed a significant increase in total count of cells and a significant neutrophil decrease. LPS induced weight loss in both strains, more pronounced in Trik. The study points out strain-specific metabolomic changes in guinea pig LPS model, highlighting the importance of strain selection in inflammation research. While descriptive, these preliminary findings provide a basis for future work to explore inflammatory mechanisms of LPS and improve translation to human disease.

急性炎症是一种复杂的生物反应，由各种入侵因子引发不同的免疫途径。由于豚鼠的菌株间变异会影响炎症反应，最终影响疾病进展，了解这些菌株特异性差异可以提高豚鼠模型在研究急性炎症中的可靠性和翻译相关性。本研究采用细菌内毒素脂多糖（LPS）诱导豚鼠Trik - coloro和Dunkin-Hartley albino两株豚鼠急性全身性炎症。采用氢-1核磁共振（¹H NMR）谱法鉴定血浆和支气管肺泡灌洗液（BALF）中特异性代谢物的变化。血浆代谢组学谱的明显差异表明，在lps诱导的急性炎症期间，循环代谢物在品系间存在显著差异，包括那些涉及氨基酸转氨化、氨转移和免疫反应的代谢物。lps诱导炎症豚鼠的BALF代谢组学分析显示，特定代谢物水平下降。此外，还评估了LPS暴露后血液和半胱氨酸白细胞计数以及体重的变化。在BALF中，LPS引起Dunkin-Hartley菌株的总细胞计数轻微但不显著增加，中性粒细胞显著增加。在血液中，Trik菌株的细胞总数明显增加，中性粒细胞明显减少。LPS诱导两种菌株的体重减轻，在Trik中更为明显。该研究指出了豚鼠LPS模型中菌株特异性代谢组学的变化，突出了菌株选择在炎症研究中的重要性。虽然是描述性的，但这些初步发现为未来探索LPS的炎症机制和改善转化为人类疾病的工作提供了基础。

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引用次数: 0

Description of three dysfunctional breathing patterns in post-COVID dyspnea covid - 19后呼吸困难的三种功能失调呼吸模式的描述。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-01-08 DOI: 10.1016/j.resp.2026.104543

Ivan Guerreiro , Aurélien Bringard , Pascal Weber , Viva Leverington , Aileen Kharat , Léon Genecand , Anna Taboni , Frédéric Lador

Introduction

Dysfunctional breathing (DB) can be defined as a change in breathing pattern associated with respiratory and/or systemic symptoms, after ruling out underlying respiratory or cardiac disease. Recent evidence suggests that DB contributes to dyspnea in post-COVID-19 syndrome (PCS), as demonstrated by ventilation analysis during cardiopulmonary exercise testing (CPET). Nevertheless, the lack of a standardized classification for the different subtypes of DB poses challenges for accurate diagnosis and effective management. We hypothesized that analyzing the evolution of breathing parameters during CPET may help classify DB into three patterns.

Methods

We analyzed 79 CPETs performed between July 2020 and May 2022 on patients with persistent respiratory symptoms at least three months after COVID-19 infection. We classified patients into three different categories based on abnormal breathing patterns: hyperventilation (HYPV), erratic breathing (ERBR), and flattening (FLAT).

Results

Age, BMI, gender and peak O₂ uptake (V̇O₂) were similar between patterns. Compared to normal pattern (N), we found higher V̇_E – V̇CO₂ slope in HYPV and FLAT, and a lower VT/ V̇_E slope in FLAT and ERBR. The FLAT pattern was also characterized by a higher breathing frequency at peak exercise compared to the other patterns. ERBR and FLAT were associated with higher symptom scores (Nijmegen Questionnaire and Dyspnea-12) compared to N.

Conclusion

Analyzing the evolution of ventilatory parameters during incremental exercise enables the classification of dysfunctional breathing into three distinct breathing patterns: hyperventilation, erratic breathing, and flattening.

简介：呼吸功能障碍（DB）可定义为排除潜在的呼吸或心脏疾病后，与呼吸和/或全身症状相关的呼吸模式改变。最近的证据表明，心肺运动试验（CPET）期间的通气分析表明，DB会导致covid -19后综合征（PCS）的呼吸困难。然而，缺乏对不同亚型DB的标准化分类给准确诊断和有效管理带来了挑战。我们假设分析CPET期间呼吸参数的演变可能有助于将DB分为三种模式。方法：我们分析了2020年7月至2022年5月期间对COVID-19感染后至少三个月出现持续呼吸道症状的患者进行的79例cpet。我们根据异常呼吸模式将患者分为三种不同的类型：换气过度（HYPV）、呼吸不稳定（ERBR）和压平（FLAT）。结果：年龄、身体质量指数、性别、最大摄氧量（V (O2)）相似。与正常模式(N)相比，我们发现HYPV和FLAT的V / E - V / CO2斜率较高，而FLAT和ERBR的VT/ V / E斜率较低。与其他模式相比，FLAT模式的另一个特点是在高峰运动时呼吸频率更高。与n相比，ERBR和FLAT与更高的症状评分（奈梅根问卷和呼吸困难-12）相关。结论：分析渐进式运动期间通气参数的演变可以将呼吸功能障碍分为三种不同的呼吸模式：换气过度、呼吸不稳定和压平。

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引用次数: 0

Tongue blade neuromuscular junction defects in old F344 rats 老龄F344大鼠舌叶神经肌肉连接缺损的研究。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-01-19 DOI: 10.1016/j.resp.2026.104545

John F. Kemp , Gary C. Sieck , Matthew J. Fogarty

Tongue-muscle associated behaviours (swallow, speech) are impaired in the elderly. In the Fischer 344 (F344) rat model of aging, hypoglossal motor neurons (MNs) and intrinsic tongue muscle weakness and atrophy are evident. Here we evaluated young (6-months) and old (24-months-old) F344 rat longitudinal muscles for neuromuscular junction (NMJ) innervation. In 140 µm free floating sections, presynaptic components were labelled with synaptophysin and neurofilament. Postsynaptic acetylcholine receptors were labelled with α-Bungarotoxin. NMJs were imaged using confocal microscopy with presynaptic invasion of the postsynaptic endplate quantified. We found marked denervation of female and male tongue NMJs in old age. Our findings are consistent with the significant role that tongue dysfunction has in aged tongue muscle dysfunction and hypoglossal MN death.

舌肌相关行为（吞咽、说话）在老年人中受损。在Fischer 344 （F344）衰老大鼠模型中，舌下运动神经元（MNs）和固有舌肌无力萎缩明显。在这里，我们评估了幼龄（6个月）和老年（24个月）F344大鼠纵向肌肉的神经肌肉接点（NMJ）神经支配。在140µm自由浮动切片上，用突触素和神经丝标记突触前成分。突触后乙酰胆碱受体用α-班加罗毒素标记。使用共聚焦显微镜对神经突触进行成像，并定量突触前终板的侵袭。我们发现老年女性和男性的舌头NMJs都有明显的去神经支配。我们的发现与舌功能障碍在老年舌肌功能障碍和舌下MN死亡中的重要作用是一致的。

引用次数: 0

Effects of postural instability on diaphragm and sternocleidomastoid recruitment during a loaded-inspiratory task in healthy adults 健康成人负重吸气时体位不稳定对膈肌和胸锁乳突肌恢复的影响。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2025-12-29 DOI: 10.1016/j.resp.2025.104541

Fang Liu , Mak Yi On , Cheung Kwan Tang , Lai In Tung , Cheung Chun Hin , Alice Y.M. Jones , William W.N. Tsang

Background

Inspiratory muscle training (IMT) is commonly used to improve inspiratory muscle strength. However, the relationship between postural stability and recruitment of inspiratory muscles during IMT remains unclear.

Objective

To investigate the effect of concurrent seated postural instability and loaded inspiratory breathing on diaphragmatic and sternocleidomastoid (SCM) muscle recruitment activities in healthy adults.

Methods

Healthy young adults performed 10 breaths with inspiratory load at 50 % Maximal Inspiratory Pressure (MIP) under four seating conditions in random order: (A) sitting on a stable surface; (B) on a balance pad with both feet on ground; (C) on a balance pad with each foot on separate balance pads; and (D) on a balance pad with both feet on a single balance pad. Right SCM and right hemidiaphragm muscle activity were recorded simultaneously using surface electromyography (sEMG) and ultrasonography, respectively. Self-perceived exertion was recorded after each task.

Results

Forty-eight healthy young adults participated in this study. Diaphragmatic contraction, as reflected by the diaphragm thickening fraction (DTf), and SCM muscle activity both increased progressively with greater seated postural instability (from position A to D). Significant incremental increases in recruitment of diaphragm and SCM were observed across all positions, and the largest and statistically significant changes were found between position A and position D, with DTf increased by 40 % (P < 0.001, 95 % CI: 31–49 %) and SCM activity by 17 % (P < 0.001, 95 % CI: 14–20 %). No significant differences in self-perceived exertion levels were observed among the seated conditions.

Conclusion

Postural instability during loaded inspiration significantly enhanced diaphragmatic contraction and moderately increased SCM activity in healthy adults. Incorporating postural challenges in IMT protocols may further enhance diaphragmatic training and warrants further study.

背景：吸气肌训练（IMT）是一种常用的提高吸气肌力量的方法。然而，在IMT过程中，体位稳定性与吸气肌恢复之间的关系尚不清楚。目的：探讨同时坐位不稳和负重吸气呼吸对健康成人膈肌和胸锁乳突肌（SCM）肌肉恢复活动的影响。方法：健康青年在四种坐姿条件下，以50%最大吸气压力（MIP）进行10次吸气负荷呼吸，随机顺序：(A)坐在稳定的表面；(B)双脚着地，站在平衡垫上；(C)在平衡垫上，每只脚放在不同的平衡垫上；(D)在平衡垫上，双脚在一个平衡垫上。采用表面肌电图（sEMG）和超声同时记录右膈肌和右膈肌活动。在每次任务后记录自我感觉的努力程度。结果：48名健康青年参加了本研究。膈肌收缩，如膈肌增厚分数（DTf）所反映的，和SCM肌活动都随着坐姿不稳定性的增加而逐渐增加（从位置A到D）。在所有体位中，膈肌和SCM的收缩都有显著的增加，其中A体位和D体位的变化最大，DTf增加了40%（结论：负重吸气时体位不稳定显著增强了健康成人的膈肌收缩，适度增加了SCM活动）。将体位挑战纳入IMT方案可以进一步加强膈肌训练，值得进一步研究。

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引用次数: 0

Invasive cardiopulmonary exercise testing: Physiologic assessment of unexplained dyspnea and exercise intolerance 有创心肺运动试验：不明原因呼吸困难和运动不耐受的生理评估。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-02-02 DOI: 10.1016/j.resp.2026.104550

Emily A. Harris, Aaron B. Waxman

Unexplained dyspnea and exertional intolerance are common, burdensome clinical problems that may persist despite routine resting cardiopulmonary testing. Invasive cardiopulmonary exercise testing (iCPET) integrates breath-by-breath gas exchange with invasive hemodynamic and blood gas assessment during incremental exercise, enabling evaluation of physiologic abnormalities that may be unapparent at rest. This review summarizes practical considerations for iCPET performance (including upright cycle ergometry, catheter-based pressure measurements, direct Fick cardiac output, and symptom assessment using separate visual analog Modified Borg ratings for dyspnea and leg fatigue at peak exercise), and presents a structured approach to interpretation using pressure–flow relationships and age-related reference ranges. Emphasis is placed on how characteristic iCPET patterns inform mechanistic contributors to exertional dyspnea by identifying upstream physiologic triggers—such as abnormal rises in pulmonary arterial wedge pressure (exercise-HFpEF), abnormal pulmonary vascular pressure–flow responses (exercise-PAH), impaired preload augmentation associated with autonomic dysfunction, and impaired peripheral oxygen extraction consistent with mitochondrial myopathy. The review also highlights evolving applications in post-pulmonary embolism syndromes and acknowledges that exercise hemodynamic thresholds and protocols vary across centers, underscoring the need for broader standardization.

原因不明的呼吸困难和运动不耐受是常见的，尽管常规静息心肺测试，但可能持续存在的繁重临床问题。有创心肺运动试验（iCPET）将渐进式运动期间的呼吸气体交换与有创血流动力学和血气评估结合起来，能够评估休息时可能不明显的生理异常。本综述总结了iCPET性能的实际考虑因素（包括直立周期几何测量，导管压力测量，直接菲克心输出量，以及使用单独的视觉模拟修正博格评分来评估呼吸困难和运动高峰时的腿部疲劳），并提出了一种使用压力-流量关系和年龄相关参考范围进行解释的结构化方法。重点是通过识别上游生理触发因素，如肺动脉wedge压异常升高（运动- hfpef），肺血管压力-血流反应异常（运动- pah），与自主神经功能障碍相关的预负荷增强受损，以及与线粒体肌病一致的外周氧提取受损，iCPET特征模式如何告知运动性呼吸困难的机制因素。该综述还强调了在肺栓塞后综合征中的不断发展的应用，并承认运动血流动力学阈值和方案因中心而异，强调需要更广泛的标准化。

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引用次数: 0

Ventilatory limitation to exercise in patients with HFpEF and obesity: No room to breathe HFpEF和肥胖患者运动时的呼吸限制：没有呼吸空间

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-01-27 DOI: 10.1016/j.resp.2026.104546

Tony G. Babb , Bryce N. Balmain , Andrew R. Tomlinson , Linda S. Hynan , Benjamin D. Levine , James P. MacNamara , Satyam Sarma

Background

Lowering pulmonary capillary wedge pressure (PCWP) by sublingual nitroglycerin (NTG) fails to increase exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF). These findings beg the question as to the origin of exercise limitation. Our objective was to determine whether exercise tolerance could be ventilatory limited in older patients with HFpEF and obesity.

Methods

Patients with HFpEF and obesity (n = 42) underwent pulmonary artery and radial artery catheterizations. Cardiorespiratory responses, breathing mechanics, and arterial blood gases were measured at rest, 20 W, and at peak exercise before and after NTG.

Results

At rest, there was a drop in cardiac output and PaO₂ (p < 0.01) with subsequent increases in HR, a-

\bar{v}

O₂ difference, and A-aO₂ difference (p < 0.001) after NTG. At 20 W, there were increases in HR, a-

\bar{v}

O₂ difference, V̇_E/V̇CO₂, lactate, PaO₂, and A-aO₂ difference (p < 0.05). At peak exercise, there was an increase in V̇_E/V̇CO₂ and pH (p < 0.01), and a decrease in PaCO₂ (p < 0.001). However, before and after treatment, there was a qualitative decline in V̇_E/V̇CO₂ from 20 W to peak exercise suggesting these patients could not increase V̇_E further. There were no differences in breathing mechanics at rest, 20 W, or peak exercise after NTG.

Conclusions

We conclude that mechanical ventilatory constraints coupled with increased ventilatory inefficiency impose a ventilatory limitation to exercise in patients with HFpEF and obesity.

Clinical Trial Information

Clinical Trials number: NCT04068844

背景：舌下硝酸甘油（NTG）降低肺毛细血管楔压（PCWP）并不能增加具有保留射血分数（HFpEF）的心力衰竭患者的运动能力。这些发现引出了运动限制的起源问题。我们的目的是确定老年HFpEF和肥胖患者的运动耐量是否会受到通气限制。方法HFpEF合并肥胖患者（n = 42）行肺动脉和桡动脉插管。在静息、20 W和NTG前后的运动高峰时测量心肺反应、呼吸力学和动脉血气。结果静息时，NTG后心输出量和PaO2下降（p <； 0.01），HR、a-v¯O2差、a- ao2差升高（p < 0.001）。在20 W时，HR、a-v¯O2差异、V (E) /V （CO2）、乳酸、PaO2和A-aO2差异均增加（p < 0.05）。运动高峰时，V / E/V / CO2和pH升高（p < 0.01）， PaCO2降低（p < 0.001）。然而，在治疗前后，患者的V (E) /V （CO2）从20 W到运动峰值有质的下降，这表明这些患者不能进一步增加V (E)。在休息、20 W或NTG后的高峰运动时呼吸力学没有差异。我们得出结论，机械通气限制加上通气效率低下的增加对HFpEF和肥胖患者的运动施加了通气限制。临床试验信息临床试验编号：NCT04068844

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引用次数: 0

Effect of superior laryngeal nerve stimulation on swallowing and respiratory coordination in dexmedetomidine-administered adult rats 喉上神经刺激对右美托咪定大鼠吞咽和呼吸协调的影响。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-01-05 DOI: 10.1016/j.resp.2026.104542

Hinata Kubota, Ryoji Ide, Nana Sato Hashizume, Eishi Nakamura, Chikako Saiki

It is not clear whether swallowing, which is induced by electrical stimulation of the superior laryngeal nerve (SLN), dominantly suppresses respiration. We examined how the swallowing coordinates with respiration in adult rats under continuous infusion of dexmedetomidine, which possesses α₂-adrenoceptor/imidazoline I₁ receptor (α₂AR/I₁R) mediated sedative-analgesic profile with minimal direct GABAergic potentiation, thereby reducing interference with swallowing circuitry. Prior to the experiment, adult rats (203–322 g, n = 12) under isoflurane anesthesia had their tail vein cannulated for dexmedetomidine administration and tail artery cannulated for analysis of arterial pressure, pulse rate, blood gases (PaO₂, PaCO₂, pH), blood glucose, hematocrit and hemoglobin. After recovery, the animals received continuous infusion of dexmedetomidine intravenously. An incision was made in the neck for SLN electrical stimulation and for recording mylohyoid electromyograms to detect swallowing. Another incision was made in the upper abdomen for recording diaphragm electromyograms to detect inspiratory movements. The spontaneously breathing animals showed no response to tactile or noxious stimulations under continuous infusion of dexmedetomidine. During SLN stimulation at different frequencies (20, 50, or 100 Hz for 10 s), the number of swallows increased in a frequency-dependent manner. Increased swallowing primarily occurred with suppressed respiration (Phase I) and thereafter occurred just after inspiration (Phase II), during which the respiratory frequency recovered to the level before stimulation. The results suggest that, in adult rats receiving dexmedetomidine, SLN stimulation not only triggers swallowing and apnea, but also allows respiration to be resumed and control the occurrence of the swallowing in coordination with respiration.

吞咽是由电刺激喉上神经（SLN）引起的，是否主要抑制呼吸尚不清楚。右美托咪定具有α2-肾上腺素能受体/咪唑啉I1受体（α2AR/I1R）介导的镇静镇痛作用，具有最小的直接gaba能增强，从而减少了对吞咽回路的干扰，我们研究了右美托咪定持续输注成年大鼠吞咽与呼吸的协调情况。实验前，异氟醚麻醉下的成年大鼠（203 ~ 322g, n = 12）尾静脉插管给予右美托咪定，尾动脉插管分析动脉压、脉搏率、血气（PaO2、PaCO2、pH）、血糖、红细胞压比和血红蛋白。恢复后，继续静脉滴注右美托咪定。在颈部做一个切口进行SLN电刺激，并记录下颌舌骨肌电图以检测吞咽。在上腹部另做一个切口，记录膈肌电图以检测吸气运动。连续输注右美托咪定后，自主呼吸动物对触觉或有害刺激无反应。在不同频率（20、50或100Hz，持续10秒）的SLN刺激期间，燕子的数量以频率依赖的方式增加。吞咽增加主要发生在呼吸抑制时（第一阶段），随后发生在吸气后（第二阶段），期间呼吸频率恢复到刺激前的水平。结果提示，在接受右美托咪定的成年大鼠中，SLN刺激不仅可以触发吞咽和呼吸暂停，还可以使呼吸恢复并控制吞咽与呼吸协调的发生。

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引用次数: 0

Quantitative morphometric analysis of asthmatic mouse lungs using micro-CT: A preclinical imaging study 应用显微ct对哮喘小鼠肺的定量形态学分析：临床前影像学研究。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-04-01 Epub Date: 2026-01-29 DOI: 10.1016/j.resp.2026.104548

Hoang Bao Lam Nguyen , Juwan Kim , Ngan-Khanh Chau , Gyuri Kim , Hyunseop Kim , Kum Ju Chae , Sujeong Kim , Kyungrim Yi , Sori Kim , Ji-Seung Yoo , Sanghun Choi

Asthma is a heterogeneous disease comprising eosinophilic (EOS) and neutrophilic (NEU) phenotypes with distinct airway and parenchymal alterations. Using murine models, this study explored phenotype-specific structural and densitometric changes that are difficult to capture in human cohorts. Sixteen female C57BL/6NCrlOri mice were assigned to negative control (n = 5), EOS (n = 6), or NEU (n = 5) asthma groups. High-resolution micro-computed tomography (micro-CT) was used to quantify airway and parenchymal alterations. Morphometric parameters included bifurcation angle (

θ

), circularity (Cr), hydraulic diameter (D_h), wall thickness (WT), and luminal volume (LV). Voxel-wise parenchymal analysis, based on CT Hounsfield unit (HU) thresholds, classified regions as emphysema-like lung, ground-glass opacity (GGO), semi-consolidation, consolidation, and fibrosis. Compared with controls, asthmatic groups showed distinct but partially overlapping structural patterns. EOS demonstrated predominant alterations in distal airways and main bronchi, with increased Cr and D_h, accompanied by higher GGO and semi-consolidation. NEU caused widespread proximal airway dilation, reflected by greater LV, but showed minimal parenchymal changes. Tracheal Cr, D_h, and LV, correlated positively with GGO and semi-consolidation, suggesting a potential association between airway enlargement and parenchymal alterations. Besides, bronchoalveolar lavage (BAL) flow cytometry confirmed distinct inflammatory endotypes, with eosinophil enrichment in EOS mice and increased neutrophils and monocytes in NEU mice. Consistently, lung histopathology showed greater peribronchial inflammation and collagen-associated airway remodeling in NEU mice, whereas EOS mice exhibited moderate inflammatory infiltration with localized matrix deposition. Overall, quantitative micro-CT differentiates EOS and NEU asthma phenotypes by capturing airway and parenchymal features, supporting non-invasive preclinical phenotyping and phenotype-targeted therapy development.

哮喘是一种异质性疾病，包括嗜酸性粒细胞（EOS）和嗜中性粒细胞（NEU）表型，具有明显的气道和实质改变。使用小鼠模型，本研究探索了在人类队列中难以捕获的表型特异性结构和密度变化。16只雌性C57BL/6NCrlOri小鼠被分为阴性对照组（n=5）、EOS组（n=6）和NEU组（n=5）。高分辨率显微计算机断层扫描（micro-CT）用于量化气道和实质改变。形态学参数包括分岔角（θ）、圆度（Cr）、水力直径（Dh）、壁厚（WT）和管腔容积（LV）。基于CT Hounsfield单位（HU）阈值的体素级实质分析，将区域分为肺气肿样肺、磨玻璃样不透明（GGO）、半实变、实变和纤维化。与对照组相比，哮喘组表现出不同但部分重叠的结构模式。EOS主要表现为远端气道和主支气管的改变，Cr和Dh升高，伴有高GGO和半实变。NEU引起广泛的近端气道扩张，反映为更大的左室，但显示最小的实质改变。气管Cr、Dh和LV与GGO和半实变呈正相关，提示气道增大与实质改变之间存在潜在关联。此外，支气管肺泡灌洗（BAL）流式细胞术证实了不同的炎症内型，EOS小鼠中嗜酸性粒细胞富集，NEU小鼠中中性粒细胞和单核细胞增加。一致地，NEU小鼠的肺组织病理学显示更大的支气管周围炎症和胶原相关的气道重塑，而EOS小鼠表现为中度炎症浸润和局部基质沉积。总体而言，定量微ct通过捕捉气道和实质特征来区分EOS和NEU哮喘表型，支持非侵入性临床前表型和表型靶向治疗的发展。

{"title":"Quantitative morphometric analysis of asthmatic mouse lungs using micro-CT: A preclinical imaging study","authors":"Hoang Bao Lam Nguyen , Juwan Kim , Ngan-Khanh Chau , Gyuri Kim , Hyunseop Kim , Kum Ju Chae , Sujeong Kim , Kyungrim Yi , Sori Kim , Ji-Seung Yoo , Sanghun Choi","doi":"10.1016/j.resp.2026.104548","DOIUrl":"10.1016/j.resp.2026.104548","url":null,"abstract":"<div><div>Asthma is a heterogeneous disease comprising eosinophilic (EOS) and neutrophilic (NEU) phenotypes with distinct airway and parenchymal alterations. Using murine models, this study explored phenotype-specific structural and densitometric changes that are difficult to capture in human cohorts. Sixteen female C57BL/6NCrlOri mice were assigned to negative control (n = 5), EOS (n = 6), or NEU (n = 5) asthma groups. High-resolution micro-computed tomography (micro-CT) was used to quantify airway and parenchymal alterations. Morphometric parameters included bifurcation angle (<span><math><mi>θ</mi></math></span>), circularity (Cr), hydraulic diameter (D<sub>h</sub>), wall thickness (WT), and luminal volume (LV). Voxel-wise parenchymal analysis, based on CT Hounsfield unit (HU) thresholds, classified regions as emphysema-like lung, ground-glass opacity (GGO), semi-consolidation, consolidation, and fibrosis. Compared with controls, asthmatic groups showed distinct but partially overlapping structural patterns. EOS demonstrated predominant alterations in distal airways and main bronchi, with increased Cr and D<sub>h</sub>, accompanied by higher GGO and semi-consolidation. NEU caused widespread proximal airway dilation, reflected by greater LV, but showed minimal parenchymal changes. Tracheal Cr, D<sub>h</sub>, and LV, correlated positively with GGO and semi-consolidation, suggesting a potential association between airway enlargement and parenchymal alterations. Besides, bronchoalveolar lavage (BAL) flow cytometry confirmed distinct inflammatory endotypes, with eosinophil enrichment in EOS mice and increased neutrophils and monocytes in NEU mice. Consistently, lung histopathology showed greater peribronchial inflammation and collagen-associated airway remodeling in NEU mice, whereas EOS mice exhibited moderate inflammatory infiltration with localized matrix deposition. Overall, quantitative micro-CT differentiates EOS and NEU asthma phenotypes by capturing airway and parenchymal features, supporting non-invasive preclinical phenotyping and phenotype-targeted therapy development.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104548"},"PeriodicalIF":1.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093898","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}

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