Respiratory Physiology & Neurobiology最新文献_第8页

The potential role of the anterior insular cortex and interoception on dyspnea in chronic obstructive pulmonary disease 慢性阻塞性肺疾病患者呼吸困难的潜在作用：前岛叶皮质和间觉

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-08-01 Epub Date: 2025-05-08 DOI: 10.1016/j.resp.2025.104441

Anna L. Hudson , Molly-Eve Day , Marie T. Williams , Olivia K. Harrison

Dyspnea (the perception of breathing discomfort) can be an immensely debilitating symptom for people with chronic obstructive pulmonary disease (COPD) and is not fully reflective of physiological measures of disease severity. We propose that the anterior insular cortex (AIC) and its key role in interoception (the perception of signals from within the body) are important mediators of dyspnea symptomology. Interoception encompasses respiratory motor drive, corollary discharge, sensory afferents, central neural integration, error signal generation, gating, decision processing and behavioral adaptation. Neuroimaging evidence supports this notion as decreased AIC activity in people with COPD is associated with heightened dyspnea, and respiratory interoceptive attention tasks have been shown to increase activation in this area of the brain. Therefore, activity in the AIC within the interoceptive processing pathway may explain some of the variability in symptom burden in people living with COPD. We explore these theories in the context of the current knowledge on the physiology and neuroscience of dyspnea, drawing on the implementation of interoceptive measures in other respiratory and mental health conditions. Given the evidence that the AIC has a key role in interoception and is a likely mediator within dyspnea symptomology, advances in our understanding of the role of interoceptive processing on symptom burden in people living with COPD, as well as appropriate methods to measure and treat it, should be research priorities.

呼吸困难（呼吸不适的感觉）对慢性阻塞性肺疾病（COPD）患者来说是一种非常虚弱的症状，并不能完全反映疾病严重程度的生理指标。我们认为，前岛叶皮层（AIC）及其在内感受（体内信号的感知）中的关键作用是呼吸困难症状的重要介质。内感受包括呼吸运动驱动、必然放电、感觉传入、中枢神经整合、错误信号产生、门控、决策处理和行为适应。神经影像学证据支持这一观点，因为慢性阻塞性肺病患者AIC活动下降与呼吸困难加剧有关，而呼吸内感受性注意力任务已被证明可增加大脑该区域的激活。因此，内感受性加工通路中AIC的活性可以解释COPD患者症状负担的一些变异性。我们在当前关于呼吸困难的生理学和神经科学知识的背景下探索这些理论，并借鉴其他呼吸和精神健康状况的内感受性措施的实施。有证据表明，AIC在间感受中起关键作用，并且可能是呼吸困难症状的中介，因此，我们对间感受加工在COPD患者症状负担中的作用的理解，以及测量和治疗的适当方法，应该是研究的重点。

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引用次数: 0

Augmented activity of suprahyoid muscles during hypothermia in sevoflurane-anesthetized mice 七氟醚麻醉小鼠低温期间舌骨上肌活动增强

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-08-01 Epub Date: 2025-05-26 DOI: 10.1016/j.resp.2025.104452

Mayumi Hashida, Takashi Nishino, Saki Taiji, Hisayo Jin, Shiroh Isono

Halogenated volatile anesthetics not only cause profound respiratory depression but also exert a facilitatory influence on the upper airway dilator (UAD) muscles in small rodents. A high concentration of sevoflurane inhalation induces gasping respiration characterized by augmented breaths with mandibular movements, to which elevated activity of suprahyoid muscles (SHMs) contributes significantly. Although similar gasping-like breathing has been observed during hypothermia in sevoflurane-anesthetized spontaneously breathing mice, the effect of sevoflurane during hypothermia on SHMs’ activity remains elusive. We investigated the synergistic effects of sevoflurane, pentobarbital, and hypothermia on ventilation and SHMs’ activity in spontaneously breathing mice. The twenty-one tracheally intubated mice were divided into three groups, i.e., the sevoflurane (N = 7), the pentobarbital (N = 7), and the pentobarbital-sevoflurane (N = 7) groups. Progressive hypothermia was produced by cooling mice in each group from 37 to 36℃ to 25–24℃ while measuring body temperature, breathing patterns, and the SHMs’ activity through subcutaneous electromyography (EMG_SH). The pentobarbital group showed minimal change in tidal volume (V_T) and respiratory-related SHMs’ activity during cooling. In contrast, in the sevoflurane and pentobarbital-sevoflurane groups, the EMG_SH, which behaves like the UAD muscle, was augmented with increased V_T during hypothermia. Notably, the pentobarbital-sevoflurane group showed significantly larger EMG_SH values at body temperatures of 34–33 and 31–30℃, indicating a more pronounced effect. Our study confirms the significant role of sevoflurane in inducing increased V_T and augmented SHMs’ activity during hypothermia. Furthermore, adding pentobarbital to sevoflurane anesthesia during hypothermia led to a further increase in augmented EMG_SH, highlighting the synergistic effects of these factors.

卤代挥发性麻醉药不仅能引起严重的呼吸抑制，还能对小型啮齿动物的上气道扩张肌（UAD）产生促进作用。高浓度的七氟醚吸入会引起喘息呼吸，其特征是伴随着下颌运动的呼吸增强，舌骨上肌（SHMs）的活动升高对此有显著贡献。虽然在经七氟醚麻醉的自主呼吸小鼠中也观察到类似的喘气样呼吸，但在低温过程中，七氟醚对SHMs活性的影响尚不清楚。我们研究了七氟醚、戊巴比妥和低温对自主呼吸小鼠通气和SHMs活性的协同作用。将21只经气管插管的小鼠分为七氟醚组（N = 7）、戊巴比妥组（N = 7）和戊巴比妥-七氟醚组（N = 7）。将各组小鼠从37 ~ 36℃降温至25 ~ 24℃，同时通过皮下肌电图（EMGSH）测量体温、呼吸方式和SHMs活性。戊巴比妥组在降温过程中潮气量（VT）和呼吸相关SHMs活性变化最小。相比之下，在七氟醚和戊巴比妥-七氟醚组中，EMGSH的行为类似于UAD肌肉，在低温期间随着VT的增加而增加。值得注意的是，戊巴比妥-七氟醚组在体温34-33℃和31-30℃时EMGSH值明显较大，表明效果更为明显。我们的研究证实了七氟醚在低温下诱导VT增加和SHMs活性增强中的重要作用。此外，在低温期间，在七氟醚麻醉中加入戊巴比妥会导致EMGSH进一步增加，这突出了这些因素的协同作用。

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引用次数: 0

Diagnostic pathways for earlier diagnosis and treatment towards better outcomes for adults living with chronic breathlessness 早期诊断和治疗成人慢性呼吸困难的诊断途径，以获得更好的结果

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-08-01 Epub Date: 2025-05-03 DOI: 10.1016/j.resp.2025.104439

Gillian E. Doe , Max Olsson , Rachael A. Evans

Chronic breathlessness is a common and distressing symptom, negatively impacting physical function and quality of life. Many individuals presenting with chronic breathlessness wait years for an explanatory diagnosis, leading to delays in accessing effective treatments and worse individual outcomes including premature mortality. In addition, delays to diagnosis are associated with increased healthcare utilisation and therefore potentially avoidable burden on healthcare systems. Diagnosing the underlying causes of chronic breathlessness is complex and can be challenging for clinicians. The current clinical diagnostic approach, related guidelines, and healthcare service structure are typically aligned with a disease-based focus. For this article, we are using a working definition of ‘Chronic Breathlessness’ to infer breathlessness that has persisted for at least eight weeks. In this narrative review, using the latest available evidence, we aimed to describe a symptom-based approach to diagnosis for adults presenting with chronic breathlessness alongside describing the potential for this approach to improve both clinical outcomes and efficiency for healthcare systems. Therefore, our objectives were to: 1) summarise what is currently known about the time to diagnosis for adults presenting with breathlessness, 2) describe the impact and possible explanations for the current delays to diagnosis, 3) describe potential solutions towards an effective symptom-based diagnosis, 4) review the potential for Artificial Intelligence (AI) to support several areas along the diagnostic pathway for breathlessness, 5) describe how a symptom-based approach to diagnosis can be directly utilised to enable a ‘matched’ personalised holistic approach to treatment.

慢性呼吸困难是一种常见且令人痛苦的症状，对身体功能和生活质量产生负面影响。许多患有慢性呼吸困难的人等待数年才能得到解释性诊断，导致获得有效治疗的延误和更糟糕的个人结果，包括过早死亡。此外，诊断延误与医疗保健利用的增加有关，因此可能会给医疗保健系统带来可避免的负担。诊断慢性呼吸困难的根本原因是复杂的，对临床医生来说可能是一个挑战。目前的临床诊断方法、相关指南和医疗保健服务结构通常与基于疾病的重点保持一致。在本文中，我们使用“慢性呼吸困难”的工作定义来推断持续至少8周的呼吸困难。在这篇叙述性综述中，我们利用最新的证据，旨在描述一种基于症状的方法来诊断成人慢性呼吸困难，同时描述这种方法改善临床结果和医疗保健系统效率的潜力。因此，我们的目标是：1)总结目前已知的成人呼吸困难的诊断时间，2)描述当前延迟诊断的影响和可能的解释，3)描述基于症状的有效诊断的潜在解决方案，4)回顾人工智能（AI）在支持呼吸困难诊断途径的几个领域的潜力。5)描述如何直接利用基于症状的诊断方法来实现“匹配的”个性化整体治疗方法。

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引用次数: 0

Effects of inspiratory muscle metaboreflex on cerebral circulation at rest and during light-intensity exercise in healthy males 健康男性休息和轻强度运动时吸气肌代谢反射对脑循环的影响

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-08-01 Epub Date: 2025-03-26 DOI: 10.1016/j.resp.2025.104422

Kohei Sato , Tatsuki Kamoda , Rintaro Sakamoto , Keisho Katayama , Toru Neki , Masaki Katayose , Erika Iwamoto

Purpose

This study aimed to clarify the effects of inspiratory muscle metaboreflex on cerebral circulation at rest and during exercise.

Methods

Twelve young males randomly completed two trials (rest and exercise [leg cycling at 40 % peak oxygen uptake] trials) on separate days. In each trial, the internal carotid artery (ICA), an index of cerebral circulation, was measured using Doppler ultrasound 2 min after inspiratory loading breathing (IL condition) or non-loading breathing (control condition). During ICA assessments, participants engaged in 3 min of spontaneous breathing (SB), followed by 3 min of isocapnic hyperventilation (IHV).

Results

ICA conductance was lower in the IL condition than in the control condition in both rest and exercise trials. Inspiratory muscle metaboreflex did not reduce ICA blood flow during SB but decreased it during IHV in both trials.

Conclusion

Our findings suggest that inspiratory muscle metaboreflex could decrease cerebrovascular conductance from rest to light-intensity exercise and attenuates cerebral blood flow with increased respiratory muscle work.

目的探讨静息和运动时吸气肌代谢反射对脑循环的影响。方法12名年轻男性在不同的日期随机完成两项试验（休息和运动[在40% %峰值摄氧量下腿部循环]试验）。在每个试验中，在吸气负荷呼吸（IL组）或非负荷呼吸（对照组）后2 min，采用多普勒超声测量颈内动脉（ICA），即脑循环指标。在ICA评估期间，参与者进行了3 min的自发呼吸（SB），随后进行了3 min的等负荷过度通气（IHV）。结果静、运动两种情况下，IL状态下的ica电导均低于对照组。在两项试验中，吸入肌代谢反射并没有减少SB期间的ICA血流量，但减少了IHV期间的ICA血流量。结论吸气肌代谢反射可以降低从休息到低强度运动的脑血管传导，并随着呼吸肌工作的增加而减弱脑血流量。

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引用次数: 0

Chemogenetic activation of the diaphragm after spinal cord injury in rats 大鼠脊髓损伤后横膈膜的化学发生激活。

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-08-01 Epub Date: 2025-03-26 DOI: 10.1016/j.resp.2025.104421

Ethan S. Benevides , Sabhya Rana , David D. Fuller

We tested the hypothesis that activation of DREADDs in the mid-cervical spinal cord could restore diaphragm activation during spontaneous breathing after cervical spinal cord injury (SCI). Adult Sprague Dawley rats (n = 7) received bilateral mid-cervical ventral horn injections of an AAV construct encoding an excitatory DREADD (AAV9-hSyn-HA-hM3D(Gq)-mCherry; titer: 2.44 × 10¹³ vg/mL). Subsequently, diaphragm electromyogram (EMG) activity was recorded during spontaneous breathing under isoflurane anesthesia. The selective DREADD ligand JHU37160 (J60) was administered intravenously at acute (3 days), sub-acute (2 weeks), and chronic (2 months) timepoints following cervical hemilesion at spinal level C2. J60 administration resulted in robust increases in diaphragm EMG output at all timepoints, and near-complete restoration of diaphragm EMG activity from the paralyzed hemi-diaphragm in 50 % of trials. Administration of J60 to DREADD naïve, spinal intact rats (n = 8) did not produce an increase in diaphragm activity. These proof-of-concept results indicate that refinement of this technique may provide a strategy for improving diaphragm activation after cervical SCI.

我们验证了一个假设，即在脊髓损伤（SCI）后，激活颈中脊髓的DREADDs可以恢复自发性呼吸时膈肌的激活。成年Sprague Dawley大鼠（n = 7）接受双侧颈中腹角注射编码兴奋性DREADD （AAV9-hSyn-HA-hM3D(Gq)-mCherry）的AAV结构；滴度：2.44×1013 vg/mL)。随后记录异氟醚麻醉下自主呼吸时膈肌电图（EMG）的活动。选择性DREADD配体JHU37160 （J60）在颈椎C2节段颈椎偏斜后的急性（3天）、亚急性（2周）和慢性（2个月）时间点静脉注射。J60在所有时间点的膈肌肌电输出均显著增加，50%的试验中瘫痪的半膈肌肌电活动几乎完全恢复。脊髓完整大鼠（n = 8）对DREADD naïve给予J60后，膈肌活动没有增加。这些概念验证结果表明，该技术的改进可能为改善颈椎脊髓损伤后膈肌激活提供了一种策略。

{"title":"Chemogenetic activation of the diaphragm after spinal cord injury in rats","authors":"Ethan S. Benevides , Sabhya Rana , David D. Fuller","doi":"10.1016/j.resp.2025.104421","DOIUrl":"10.1016/j.resp.2025.104421","url":null,"abstract":"<div><div>We tested the hypothesis that activation of DREADDs in the mid-cervical spinal cord could restore diaphragm activation during spontaneous breathing after cervical spinal cord injury (SCI). Adult Sprague Dawley rats (n = 7) received bilateral mid-cervical ventral horn injections of an AAV construct encoding an excitatory DREADD (AAV9-hSyn-HA-hM3D(Gq)-mCherry; titer: 2.44 × 10<sup>13</sup> vg/mL). Subsequently, diaphragm electromyogram (EMG) activity was recorded during spontaneous breathing under isoflurane anesthesia. The selective DREADD ligand JHU37160 (J60) was administered intravenously at acute (3 days), sub-acute (2 weeks), and chronic (2 months) timepoints following cervical hemilesion at spinal level C2. J60 administration resulted in robust increases in diaphragm EMG output at all timepoints, and near-complete restoration of diaphragm EMG activity from the paralyzed hemi-diaphragm in 50 % of trials. Administration of J60 to DREADD naïve, spinal intact rats (n = 8) did not produce an increase in diaphragm activity. These proof-of-concept results indicate that refinement of this technique may provide a strategy for improving diaphragm activation after cervical SCI.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"336 ","pages":"Article 104421"},"PeriodicalIF":1.9,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743516","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

Ventilatory response and dyspnea on exertion in children with obesity and respiratory symptoms 肥胖和呼吸症状患儿用力时的呼吸反应和呼吸困难

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-07-01 Epub Date: 2025-04-22 DOI: 10.1016/j.resp.2025.104437

Daniel P. Wilhite , Dharini M. Bhammar , Bryce N. Balmain , Tanya Martinez-Fernandez , Yulun Liu , Tony G. Babb

We investigated whether the exercise ventilatory response is associated with dyspnea on exertion (DOE) in children with (CWO;n = 25) and without (CWOO;n = 49) obesity, and with obesity and respiratory symptoms (CWORS;n = 14). The ventilatory response to exercise (V̇_E/V̇CO₂ slope) and ratings of perceived breathlessness (RPB, Borg 0–10 scale) were measured during 6-min cycling at 45 % maximal work rate. The V̇_E/V̇CO₂ slope (CWOO=34 ± 7; CWO=34 ± 5; CWORS=37 ± 6) and RPB (CWORS=4.0 ± 3.4; CWOO=2.5 ± 1.7; CWO=3.2 ± 2.1) were similar among groups (p > 0.05). A significant association between the V̇_E/V̇CO₂ slope and RPB in CWORS (r²=0.49;p < 0.05) was observed. To investigate this relationship more closely, children with an RPB≤ 2 were classified as having no or mild DOE (-DOE;n = 39;RPB=1.2 ± 0.7), and those with RPB≥ 3 were classified as having moderate to severe DOE (+DOE;n = 49;RPB=4.7 ± 1.9). +DOE had a higher V̇_E/V̇CO₂ slope (+DOE=36 ± 6;-DOE=33 ± 5;p = 0.02), higher breathing frequency, and higher V̇_E (%max;p < 0.05). These findings suggest a heightened sensitivity to ventilatory demand among children, and that +DOE may be driven by factors other than obesity alone, possibly increased ventilatory response to exercise.

我们调查了患有（CWO;n = 25）和没有（CWOO;n = 49）肥胖以及肥胖和呼吸道症状（CWORS;n = 14）的儿童的运动通气反应是否与用力时呼吸困难（DOE）相关。在45 %最大工作速率下骑行6分钟，测量运动通气反应（V / E/V / CO2斜率）和感知呼吸困难评分（RPB， Borg 0-10评分）。V (E) /V （CO2）斜率(CWOO=34 ± 7；CWO = 34 ± 5;CWORS=37 ± 6)和RPB (CWORS=4.0 ± 3.4；CWOO = 2.5 ± 1.7;CWO=3.2 ± 2.1)组间差异无统计学意义（p >； 0.05）。CWORS的V (E) /V （CO2）斜率与RPB之间存在显著相关性（r2=0.49;p <； 0.05）。探讨这种关系更密切,孩子离≤ 2被归类为没有或轻微能源部(DOE; n = 39;强化= 1.2 ±0.7 ),和那些离≥ 3被划分中度到重度的DOE(+能源部;n = 49;强化= 4.7 ±1.9 )。+DOE具有较高的V (E) /V (E) / CO2斜率（+DOE=36 ± 6;-DOE=33 ± 5;p = 0.02）、较高的呼吸频率和较高的V (E) （%max;p <； 0.05）。这些发现表明儿童对通气需求的敏感性提高，并且+DOE可能是由肥胖以外的因素驱动的，可能是运动对通气反应的增加。

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引用次数: 0

Roflumilast, a phosphodiesterase-4 (PDE4) inhibitor, induces respiratory frequency plasticity that is resistant to inflammation in neonatal rat in vitro preparations 罗氟司特（一种磷酸二酯酶-4 (PDE4)抑制剂）可诱导新生大鼠体外制备的呼吸频率可塑性，这种可塑性对炎症具有抵抗力

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-07-01 Epub Date: 2025-04-13 DOI: 10.1016/j.resp.2025.104435

Stephen M. Johnson, Jacob P. Rastas, Pujal S. Desai, Tracy L. Baker, Jyoti J. Watters

Premature and newborn infants often have prolonged apneas and are susceptible to bacterial infections that further disrupt breathing. Phoshodiesterase-4 (PDE4) inhibitor drugs increase inspiratory motor activity and appear to induce a long-lasting increase in inspiratory frequency (“frequency plasticity”). To test whether a PDE4 inhibitor drug induces frequency plasticity, neonatal rat brainstem-spinal cords were isolated and exposed to bath-applied roflumilast (10 min, 0.02–1.0 µM). Roflumilast acutely increased burst frequency and induced frequency plasticity in a concentration-dependent manner. Blockade of protein kinase A (PKA) or exchange protein activated by cAMP (EPAC) signaling pathways abolished the induction, but not the maintenance, of roflumilast-induced frequency plasticity. Brainstem-spinal cords isolated from neonatal rats injected with lipopolysaccharide (LPS, 0.1 mg/kg, 3 h prior) expressed frequency plasticity following bath-applied roflumilast at 0.05–0.5 µM, but not at lower concentrations. This shows that roflumilast-induced frequency plasticity is largely resistant to LPS-induced inflammation. Thus, roflumilast increases inspiratory burst frequency acutely and induces frequency plasticity even during ongoing inflammation, which could have important clinical implications.

早产儿和新生儿经常会出现长时间的呼吸暂停，并容易受到细菌感染，从而进一步影响呼吸。磷酸二酯酶-4（PDE4）抑制剂药物会增加吸气运动活动，似乎会诱导吸气频率的长期增加（"频率可塑性"）。为了测试 PDE4 抑制剂药物是否会诱导频率可塑性，我们分离了新生大鼠的脑干脊髓，并将其置于沐浴施用的罗氟司特（10 分钟，0.02-1.0 µM）中。罗氟司特能以浓度依赖性方式急性增加爆发频率并诱导频率可塑性。阻断蛋白激酶A（PKA）或cAMP激活的交换蛋白（EPAC）信号通路可消除罗氟司特诱导的频率可塑性的诱导，但不能维持这种可塑性。从注射了脂多糖（LPS，0.1 毫克/千克，3 小时前）的新生大鼠身上分离出的脑干脊髓在沐浴施用 0.05-0.5 µM 罗氟司特后表现出频率可塑性，但在较低浓度下则没有。这表明罗氟司特诱导的频率可塑性在很大程度上能抵抗 LPS 诱导的炎症。因此，罗氟司特能快速增加吸气爆发频率，即使在炎症持续期间也能诱导频率可塑性，这可能具有重要的临床意义。

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引用次数: 0

GAA replacement improves respiratory muscle, neural, and alveolar pathology in the pompe mouse GAA替代改善pompe小鼠的呼吸肌、神经和肺泡病理

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-07-01 Epub Date: 2025-04-25 DOI: 10.1016/j.resp.2025.104433

Angela L. Roger , Lea El Haddad , Meredith L. Huston , Sean Kehoe , Davina Le , Mainur Khan , Evelyn Scarrow , Trevor Gonzalez , Abigail Benkert , Aravind Asokan , Mai K. ElMallah

Pompe disease is a devastating neuromuscular disorder caused by mutations in the gene GAA. These mutations result in a deficiency of the enzyme acid α-glucosidase (GAA), leading to lysosomal glycogen accumulation in cardiac, skeletal, and smooth muscle, motor neurons, and alveolar epithelial cells. Respiratory failure due to neuromuscular weakness, recurrent aspiration pneumonia, and tracheo-bronchomalacia are the leading causes of morbidity and mortality in PD patients. Enzyme replacement therapy (ERT) is currently the only FDA approved treatment for Pompe disease, however, gene therapy with naturally occurring and engineered adeno-associated viral vectors are also widely studied as an alternative treatment. In the present study we directly compared the benefits of existing and novel treatment modalities - ERT, AAV9-GAA, and AAVcc47-GAA, with an emphasis on correction of pathologies related to respiratory function. We find that GAA replacement in early adult mice improves respiration through 9 months of age. This improvement is attributed to glycogen clearance in the tongue, diaphragm, and lungs, which subsequently improved diaphragm neuromuscular junctions and reduced lysosomes within the alveolar epithelia.

庞贝病是一种由GAA基因突变引起的毁灭性神经肌肉疾病。这些突变导致α-葡萄糖苷酶（GAA）缺乏，导致溶酶体糖原在心脏、骨骼、平滑肌、运动神经元和肺泡上皮细胞中积累。神经肌肉无力引起的呼吸衰竭、反复吸入性肺炎和气管支气管软化是PD患者发病和死亡的主要原因。酶替代疗法（ERT）是目前FDA批准的唯一治疗Pompe病的方法，然而，使用自然发生和工程化腺相关病毒载体的基因治疗也被广泛研究作为一种替代治疗方法。在本研究中，我们直接比较了现有的和新的治疗方式- ERT， AAV9-GAA和AAVcc47-GAA的益处，重点是纠正与呼吸功能相关的病理。我们发现，成年早期小鼠的GAA替代改善了9个月大的呼吸。这种改善是由于舌、膈和肺中的糖原清除，从而改善膈神经肌肉连接，减少肺泡上皮内的溶酶体。

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引用次数: 0

Bulk and regional diaphragm blood flow during chemical hyperpnea in pulmonary hypertensive rats 肺动脉高压大鼠化学呼吸过度时的大容量和区域膈血流量。

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-07-01 Epub Date: 2025-02-17 DOI: 10.1016/j.resp.2025.104414

Kiana M. Schulze , Andrew G. Horn , Ramona E. Weber , K. Sue Hageman , Britton C. Scheuermann , Carl J. Ade , Bradley J. Behnke , David C. Poole , Timothy I. Musch

Pulmonary hypertension (PH) is a disease characterized by increased pulmonary arterial pressures, impaired gas exchange, dyspnea, and diaphragmatic dysfunction. Specifically, in PH, the diaphragm displays impaired contractility, vascular dysfunction, and blood flow redistribution toward less mechanically advantageous regions such as the ventral costal and crural diaphragm at rest and during submaximal exercise. While diaphragm blood flow is not a limitation to maximal exercise in health, whether it limits diaphragm function in PH is unknown. We hypothesized that, during chemically induced hyperpnea: 1) diaphragm blood flow will be lower in rats with PH compared with healthy controls due to vasodilatory impairments in the diaphragm vasculature, and 2) in PH, blood flow will be redistributed toward less mechanically advantageous regions of the diaphragm. Female Sprague-Dawley rats were randomized into healthy (n = 12) or monocrotaline-induced PH (n = 12) groups. Fluorescent microspheres were used to determine bulk and regional diaphragm blood flow at rest and during hypoxic-hypercapnic gas inhalation (10 % O₂-8 % CO₂). During chemically induced hyperpnea, diaphragm blood flow was higher in PH compared with healthy controls (483 ± 102 vs. 298 ± 119 ml/min/100 g; P < 0.001), and the ventral costal and crural regions of the diaphragm supported greater perfusion in PH. These results are consistent with previous findings at rest and during submaximal exercise in PH, which may help explain diaphragmatic weakness and dyspnea across a range of ventilatory demands in PH.

肺动脉高压（PH）是一种以肺动脉压升高、气体交换受损、呼吸困难和膈功能障碍为特征的疾病。具体来说，在PH下，膈肌在休息和次极限运动时表现出收缩性受损，血管功能障碍，血流重新流向机械上不太有利的区域，如腹侧肋膈和脚膈。虽然膈血流量并不是健康状态下最大运动的限制，但它是否限制了PH值下膈血的功能尚不清楚。我们假设，在化学诱导的呼吸急促过程中：1)与健康对照相比，PH大鼠的膈血流量会减少，因为膈血管的血管扩张功能受损；2)PH大鼠的血流量会重新分布到机械上不太有利的膈区域。雌性Sprague-Dawley大鼠随机分为健康组（n=12）和单藜碱诱导PH组（n=12）。荧光微球用于测定静息和低氧-高碳酸气体吸入（10% O2-8% CO2）时的整体和区域隔膜血流量。化学诱导呼吸急促时，膈血流量PH值高于健康对照组(483±102 vs 298±119ml/min/100g；P

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引用次数: 0

Neurophysiological mechanisms of exertional dyspnea in advanced pregnancy: A case study 妊娠晚期用力性呼吸困难的神经生理机制：一个案例研究

IF 1.9 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-07-01 Epub Date: 2025-04-18 DOI: 10.1016/j.resp.2025.104434

Devin B. Phillips , Christine A. Darko , Matthew D. James , Sandra G. Vincent , Alexandra M. McCartney , Lara K. Sreibers , Nicolle J. Domnik , J. Alberto Neder , Denis E. O’Donnell

The neurophysiological mechanisms of exertional dyspnea in advanced pregnancy remain incompletely understood. This short case report describes the neurophysiological and sensory responses during standardized cardiopulmonary exercise testing (CPET) in one healthy adult female at three timepoints: a) 3 months pre-pregnancy, b) 35 weeks pregnant (third trimester [T3]), and, c) 1 year post-partum. At rest and during exercise, detailed measurements of neurophysiological, gas-exchange and sensory parameters were completed. Compared to both pre-pregnancy and post-partum, ventilatory requirements, electrical activation of the diaphragm (EMGdi, index of inspiratory neural drive) and esophageal pressure swings were higher in T3 throughout exercise. Moreover, at a given work rate, perceived dyspnea was greater in T3 compared with pre-pregnancy and post-partum and increased in close association with heightened EMGdi throughout exercise. At peak exercise in T3, dyspnea/ventilation and EMGdi/ventilation ratios were greater, compared with pre-pregnancy and post-partum. Compared with pre-pregnancy, EMGdi and perceived dyspnea were greater post-partum near the limits of exercise tolerance, secondary to earlier onset of respiratory compensation-mediated increases in ventilation. In the current case, advanced pregnancy was associated with markedly elevated ratings of dyspnea and lower exercise capacity during a standardized clinical CPET. At submaximal intensities, the heightened dyspnea reflected the awareness of pregnancy-induced increases in ventilatory requirements, inspiratory neural drive, and respiratory muscle effort. At the limits of tolerance, heightened dyspnea and inspiratory neural drive reflected a complex combination of increase ventilatory requirements and mechanical constraints on tidal volume expansion. Compared with pre-pregnancy, residual activity-related dyspnea 1-year post-partum appears to reflect physical deconditioning.

妊娠晚期劳力性呼吸困难的神经生理机制尚不完全清楚。这篇简短的病例报告描述了一名健康成年女性在三个时间点进行标准化心肺运动试验（CPET）时的神经生理和感觉反应：a)孕前3个月，b)怀孕35周（妊娠晚期[T3]）， c)产后1年。在休息和运动时，完成神经生理、气体交换和感觉参数的详细测量。与孕前和产后相比，在整个运动过程中，T3的通气需求、膈肌电激活（EMGdi，吸气神经驱动指数）和食管压力波动都更高。此外，在给定的工作速率下，与孕前和产后相比，T3期的呼吸困难更大，并且与运动过程中EMGdi的升高密切相关。在T3运动高峰时，与孕前和产后相比，呼吸困难/通气和EMGdi/通气比更大。与孕前相比，产后EMGdi和呼吸困难更大，接近运动耐量的极限，继发于早期呼吸代偿介导的通气增加。在本病例中，在标准化临床CPET中，妊娠晚期与呼吸困难评分明显升高和运动能力降低相关。在次极大强度下，呼吸困难加重反映了妊娠引起的通气需求、吸气神经驱动和呼吸肌用力增加的意识。在耐受极限下，呼吸困难加剧和吸气神经驱动反映了通气需求增加和潮汐容量扩张的机械约束的复杂组合。与孕前相比，产后1年的残余活动相关呼吸困难似乎反映了身体状况的改善。

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