Respiratory Physiology & Neurobiology最新文献_第5页

Cinnamaldehyde modulates oxidative stress and NF-κB signaling in OVA-induced asthmatic BALB/c mice 肉桂醛调节ova诱导的哮喘BALB/c小鼠的氧化应激和NF-κB信号通路。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-01-01 Epub Date: 2025-10-04 DOI: 10.1016/j.resp.2025.104497

Bsma Hassan Nour, Noha A. Mahana, Ayman Saber Mohamed, Abeer Mahmoud Badr, Hadeer Hesham Abdelfattah

Asthma remains a challenging condition with limited treatment options. Cinnamaldehyde (Cinn), a compound that is naturally recognized for its anti-inflammatory and antioxidant capabilities, has garnered considerable scientific interest. This study aims to evaluate the effects of low and high doses of Cinn compared to dexamethasone (Dexa), a conventional corticosteroid, in a murine model of ovalbumin (OVA)-induced asthma. Asthma was generated in BALB/c mice through OVA sensitization and challenge. The mice were categorized into five groups (n = 8): Control, OVA, Cinn (20 mg/kg), Cinn (40 mg/kg), and Dexa (1 mg/kg). The investigation evaluated airway inflammation, histological alterations, and inflammatory biomarkers for a duration of 16 days. Treatments were administered orally from days 11–16. Cinn administration significantly reduced oxidative stress, as indicated by reduced levels of nitric oxide and malondialdehyde, while simultaneously boosting antioxidant defenses through elevated glutathione and catalase levels. The Cinn-treated groups exhibited a significant reduction in serum immunoglobulin E levels, serum interleukin-13 (IL-13), and immune cell infiltration in bronchoalveolar lavage fluid (BALF), as well as decreased peribronchial inflammation and goblet cell metaplasia in lung histology. Moreover, Cinn inhibited the expression of nuclear factor kappa B (NFκB-p65) in lung tissues, resulting in decreased immune cell infiltration in BALF, as well as reduced peribronchial inflammation and goblet cell metaplasia. Both dosages of Cinn markedly reduced airway inflammation and histological changes relative to the OVA group, with results similar to those of Dexa, particularly at the higher dose. The data indicate that Cinn demonstrates significant anti-inflammatory and antioxidant properties, making it a promising candidate for the prevention and treatment of asthma.

哮喘仍然是一种具有挑战性的疾病，治疗方案有限。肉桂醛（Cinn）是一种天然公认的抗炎和抗氧化能力的化合物，已经引起了相当大的科学兴趣。本研究旨在评估低剂量和高剂量Cinn与地塞米松（Dexa）（一种常规皮质类固醇）在卵清蛋白（OVA）诱导哮喘小鼠模型中的作用。BALB/c小鼠通过OVA致敏和激发产生哮喘。将小鼠分为5组（n = 8）：对照组、OVA组、Cinn组（20mg/kg）、Cinn组（40mg/kg）、Dexa组（1mg/kg）。该研究评估了气道炎症、组织学改变和炎症生物标志物，持续16天。从第11天至第16天口服治疗。通过降低一氧化氮和丙二醛水平，Cinn可以显著降低氧化应激，同时通过提高谷胱甘肽和过氧化氢酶水平增强抗氧化防御。cinn处理组血清免疫球蛋白E水平、血清白细胞介素-13 （IL-13）和支气管肺泡灌洗液（BALF）免疫细胞浸润显著降低，支气管周围炎症和肺组织杯状细胞化生明显减少。此外，Cinn抑制肺组织中磷核因子κB （p-NFκB-p65）的表达，导致BALF中免疫细胞浸润减少，支气管周围炎症和杯状细胞化生减少。与OVA组相比，两种剂量的Cinn均可显著降低气道炎症和组织学改变，其结果与Dexa相似，特别是在较高剂量时。这些数据表明，Cinn具有显著的抗炎和抗氧化特性，使其成为预防和治疗哮喘的有希望的候选者。

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引用次数: 0

Metabolic and ventilatory constraints in long COVID individuals 长冠个体的代谢和通气限制

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2026-01-01 Epub Date: 2025-10-10 DOI: 10.1016/j.resp.2025.104504

Imane Salmam , Jean Tittley , Gilles Drouin , Kadija Perreault , François Desmeules , Jean-Sébastien Paquette , Jean-Sébastien Roy , Krista L. Best

Long COVID is characterized by persistent symptoms and physiological impairments beyond acute infection. Oxygen consumption (VO₂) and ventilatory efficiency, key indicators of cardiorespiratory fitness, are commonly diminished in this population, contributing to exercise intolerance. This study compared cardiorespiratory patterns and exercise capacity among individuals with Long COVID (LCG), those with resolved symptoms (Short COVID; SCG), and healthy controls (CG). The secondary objective was to assess longitudinal changes over six months. Cross-sectional comparisons at baseline addressed the primary objective, while the longitudinal component explored on changes over time. Participants included 94 in the LCG, 100 in the SCG, and 70 in the CG. All performed a 6-minute walk test (6MWT) during which peak oxygen uptake (VO₂_peak), minute ventilation (VE), and VE/VCO₂ (ratio of VE to carbon dioxide output, reflecting ventilatory efficiency) were continuously measured using the Metamax 3B system. Baseline differences were assessed by one-way ANOVA, and longitudinal changes by generalized estimating equations. At baseline, VO₂_peak was significantly reduced in the LCG (70.1 % predicted) versus SCG (80.6 %) and CG (84.6 %) (p = 0.001). VE/VCO₂ was elevated in the LCG (30.2 ± 4.2) compared to SCG (27.9 ± 2.8) and CG (28.7 ± 3.3) (p < .001). The 6MWT distance was also lower in the LCG (484 ± 127 m) than SCG (607 ± 69.1 m) and CG (571 ± 89.6 m) (p < .001). No statistically significant Group × Time interaction emerged between the groups. Individuals with Long COVID exhibited persistent ventilatory inefficiency and reduced exercise capacity, with impairments persisting over six months, underscoring the need for targeted rehabilitation.

Short abstract

Individuals with Long COVID exhibit reduced exercise capacity and persistent ventilatory inefficiency compared to Short COVID and control groups. At baseline and over six months, VO₂, VE/VCO₂, and 6MWT distances were significantly impaired, highlighting the need for targeted rehabilitation strategies to address ongoing physiological limitations in this population.

长冠肺炎的特点是急性感染以外的持续症状和生理损伤。作为心肺健康的关键指标，耗氧量（vo2）和通气效率在这一人群中普遍降低，导致运动不耐受。本研究比较了长COVID （LCG）、症状缓解（短COVID； SCG）和健康对照（CG）患者的心肺模式和运动能力。次要目标是评估六个月以上的纵向变化。基线的横断面比较解决了主要目标，而纵向成分则探讨了随时间的变化。参与者包括94名LCG组，100名SCG组和70名CG组。所有患者都进行了6分钟步行测试（6MWT），在此期间，使用Metamax 3B系统连续测量峰值摄氧量（vo2峰值）、分钟通气量（VE）和VE/VCO₂（VE与二氧化碳输出的比率，反映通风效率）。基线差异采用单因素方差分析，纵向变化采用广义估计方程。基线时，LCG组的VO 2峰值（预测值为70.1 %）明显低于SCG组（80.6 %）和CG组（84.6 %）（p = 0.001）。LCG组VE/VCO₂（30.2 ± 4.2）高于SCG组（27.9 ± 2.8）和CG组（28.7 ± 3.3）（p <； .001）。6 mwt距离也是低LCG(484 ± 127 米)比SCG(607 ±69.1  m)和CG(571 ±89.6  米)(p & lt; 措施)。组间无统计学意义 时间交互作用。长COVID患者表现出持续的通气效率低下和运动能力下降，损伤持续超过6个月，强调需要有针对性的康复。与短COVID和对照组相比，长COVID个体表现出运动能力降低和持续通气效率低下。在基线和6个月后，VO₂，VE/VCO₂和6MWT距离明显受损，强调需要有针对性的康复策略来解决该人群持续的生理限制。

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引用次数: 0

Diethelm Richter (1943-2025); a life in Respiratory Neurobiology. Diethelm Richter (1943-2025)；呼吸神经生物学的生活。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-25 DOI: 10.1016/j.resp.2025.104524

K Michael Spyer, Julian F R Paton

引用次数: 0

Effects of prior self-control exertion on breathing effort during inspiratory loading 吸气负荷时，先前自我控制努力对呼吸努力的影响

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-01 Epub Date: 2025-08-17 DOI: 10.1016/j.resp.2025.104475

Michael A. Johnson, Graham R. Sharpe, James C. Brown, Ruth Boat

Introduction

Self-control reflects the effortful inhibition of attentional, behavioural, and emotional impulses to achieve a desired long-term goal. Prior self-control exertion does not affect air hunger and tolerance to progressive hypercapnia, but whether it affects the mechanistically distinct sense of breathing effort remains unknown.

Methods

Fourteen healthy young adults (13 males, 1 female) initially completed three familiarisation trials comprising an incremental inspiratory pressure-threshold loading (IPTL) test, which began at a load of 10 cmH₂O followed by a 10 cmH₂O increase every minute until task failure. Thereafter, participants completed three experimental trials comprising IPTL preceded by rest (Control; CTRL), a congruent Stroop task (CONG) requiring no self-control exertion, or an incongruent Stroop task (INCONG) requiring self-control exertion. Breathing effort was measured at the end of each threshold load.

Results

Time to task failure during IPTL was 13 % shorter in INCONG (8.60 ± 1.69 min) than CTRL (9.96 ± 1.79 min) and CONG (9.87 ± 1.57 min) (P < 0.001). The maximum sustainable threshold pressure sustained for a full 1 min was lower in INCONG (84 ± 19 cmH₂O) than CTRL (96 ± 18 cmH₂O) and CONG (99 ± 17 cmH₂O) (P < 0.001). The rate of increase in breathing effort during IPTL was greater in INCONG (0.14 ± 0.03 A.U./cmH₂O) than CTRL (0.12 ± 0.03 A.U./cmH₂O) (P = 0.016) and CONG (0.12 ± 0.03 A.U./cmH₂O) (P = 0.014).

Conclusion

Prior self-control exertion increased the sense of breathing effort and reduced time to task failure during subsequent IPTL. These findings suggest that the sense of breathing effort is modulated by state self-control.

自我控制反映了对注意力、行为和情绪冲动的努力抑制，以达到预期的长期目标。先前的自我控制运动不会影响空气饥饿和对进行性高碳酸血症的耐受性，但它是否会影响机械上不同的呼吸努力感仍然未知。方法14名健康年轻人（13名男性，1名女性）最初完成了3项熟悉试验，其中包括增量吸气压力阈值负荷（IPTL）试验，该试验从10 cmH2O负荷开始，随后每分钟增加10 cmH2O直到任务失败。之后，参与者完成了三个实验，包括IPTL前休息（Control； CTRL）、不需要自我控制的一致性Stroop任务（CONG）和需要自我控制的不一致性Stroop任务（INCONG）。在每次阈值负荷结束时测量呼吸努力。ResultsTime任务失败在IPTL 13 %短INCONG(8.60 ±1.69  min)比CTRL(9.96 ±1.79  min)和CONG(9.87 ±1.57  min) (P & lt; 0.001)。最大可持续阈值压力持续整整1 分钟低INCONG(84 ± 19 cmH2O)比CTRL(96 ± 18 cmH2O)和CONG(99 ± cmH2O 17日)(P & lt; 0.001)。在IPTL期间，INCONG组的呼吸努力增加率（0.14 ± 0.03 a.u /cmH2O）高于CTRL组（0.12 ± 0.03 a.u）/cmH2O) （P = 0.016）和CONG（0.12 ± 0.03 ）/ cmH2O) (P = 0.014)。结论先前的自我控制运动增加了后续IPTL中呼吸力竭感，减少了任务失败时间。这些发现表明，呼吸努力的感觉是由状态自我控制调节的。

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引用次数: 0

Determination of PAO2 by the “ideal” alveolar gas concept and by miget in ventilated animals 用“理想”肺泡气体的概念和在通气动物中用可能的方法测定PAO2

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-01 Epub Date: 2025-08-19 DOI: 10.1016/j.resp.2025.104474

Gerardo Tusman , Stephan H. Böhm , Fernando Suarez-Sipmann

The Ideal Alveolar Gas Concept calculates the alveolar partial pressure of oxygen (PAO₂) using arterial (PaCO₂) instead of alveolar (PACO₂) partial pressures of carbon dioxide in the alveolar gas equation. We compared the effects of shunt on PAO₂ calculated by the “ideal” gas concept with a calculation using the multiple inert gas elimination technique (MIGET). We tested the hypothesis that shunt affects PACO₂ and introduces significant errors in the estimation of PAO₂ in two experimental porcine models. First, in a lung-lavage model (n = 10), shunt changes were induced by applying different levels of positive end-expiratory pressure. PaCO₂ median 71 mmHg, (IQR 21 mmHg) was higher than MIGET PACO₂ 52(20) mmHg (p < 0.001). Ideal PAO₂ 654(33) mmHg was lower than MIGET PAO₂ 670(19) mmHg (p < 0.001). Bias in PAO₂ was −23 mmHg with limits of agreement between 19 to −65 mmHg. Second, in a one-lung ventilation model (n = 10), changes in shunt were performed decreasing cardiac output by inferior vena cava balloon inflations (OLV_CB), inhibiting hypoxic pulmonary constriction with nitroprusiate (OLV_NPS) and increasing cardiac output with dobutamine (OLV_DBT). Baseline PaCO₂ was 55(10) mmHg and shunt 9(19)%. Cardiac output reduction did not affect PaCO₂ 57(9) mmHg (p = 0.19) or shunt 9(15)% (p = 0.570). Inhibiting hypoxic pulmonary vasoconstriction increased PaCO₂ [62(13) mmHg; p = 0.083] and shunt [26(20)%; p = 0.020]. Cardiac output increase resulted in higher PaCO₂ [67(11) mmHg; p = 0.004] and shunt [30(29)%; p = 0.012]. The assumption of the ideal gas concept that PaCO₂ is not affected by shunt is incorrect introducing significant estimation errors in the alveolar gas equation.

理想肺泡气体概念在肺泡气体方程中使用动脉（PaCO2）而不是肺泡（PaCO2）二氧化碳分压来计算肺泡氧分压（PAO2）。我们比较了分流对“理想”气体概念计算的PAO2的影响，以及使用多重惰性气体消除技术（MIGET）计算的PAO2。我们检验了分流影响PACO2的假设，并在两种实验猪模型中引入了PAO2估计的显著误差。首先，在肺灌洗模型（n = 10）中，施加不同水平的呼气末正压诱导分流改变。PaCO2中位值71 mmHg，（IQR 21 mmHg）高于MIGET PaCO2 52(20) mmHg （p <； 0.001）。理想PAO2 654(33) mmHg低于MIGET PAO2 670(19) mmHg （p <； 0.001）。PAO2的偏倚为- 23 mmHg，一致限度在19至- 65 mmHg之间。其次，在单肺通气模型（n = 10）中，通过下腔静脉球囊充气（OLVCB）降低心输出量，硝普酸（OLVNPS）抑制缺氧肺收缩，多巴酚丁胺（OLVDBT）增加心输出量。基线PaCO2为55(10)mmHg，分流率为9(19)%。心输出量减少不影响PaCO2 57(9) mmHg （p = 0.19）或分流9(15)% （p = 0.570）。抑制缺氧肺血管收缩增加PaCO2 [62(13) mmHg；P = 0.083]和分流[26(20)%；p = 0.020]。心输出量增加导致PaCO2升高[67(11)mmHg；P = 0.004]和分流[30(29)%；p = 0.012]。理想气体概念中PaCO2不受分流影响的假设是不正确的，在肺泡气体方程中引入了显著的估计误差。

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引用次数: 0

Respiratory effects of obesity on the ventilatory response to exercise in older adults: the impact of a shift in operational lung volumes 肥胖对老年人运动后通气反应的呼吸效应：手术肺容量变化的影响

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-04 DOI: 10.1016/j.resp.2025.104488

Abidan Abulimiti , Bryce N. Balmain , Jessica N. Alcala , Raksa B. Moran , Chetan Dholakiya , Raquel Cavazos , Lindsey Elwell , Marcus Payne , Rebekah Summerall Woodward , Satyam Sarma , Valentin Mons , Andrew R. Tomlinson , Tony G. Babb

We examined the exercise ventilatory response to heavy exercise (ventilation [V̇_E] and carbon dioxide elimination [V̇CO₂] relationship from ventilatory threshold to peak exercise) and operational lung volumes (end expiratory [EELV] and end inspiratory [EILV]) in older adults with and without obesity. Forty-nine older adults with (BMI: 33.9 ± 5.0 kg/m², age: 70 ± 2 y) and without obesity (BMI: 24.6 ± 3.0 kg/m², age:71 ± 3 y) were evaluated, and performed a maximal incremental cycling test. The V̇_E/V̇CO₂ slope was lower in those with (43.1 ± 8.0) vs. without obesity (51.4 ± 11.1). While EELV was lower in those with (52.4 ± 6.1 %TLC) vs. without obesity (58.9 ± 5.8 %TLC), EILV was similar (with obesity: 88.2 ± 4.5 vs. without obesity: 89.2 ± 4.2 %TLC) between groups. EELV increased more from rest to peak exercise in those with obesity (0.23 ± 0.30 L: vs. −0.1 ± 0.4 L). Our findings demonstrate that the ventilatory response to heavy exercise is blunted in older adults with obesity, which appears to be associated with an increasing EILV encroaching on TLC.

我们研究了有肥胖和没有肥胖的老年人对大运动量运动的运动通气反应(通气[V （E)]和二氧化碳消除[V (CO2)]从通气阈值到运动峰值的关系）和操作肺容量（呼气末[EELV]和吸气末[EILV]）。49老年人和(BMI: 33.9 ±5.0  kg / m2,年龄:70年 ±2  y)和没有肥胖(体重指数:24.6 ±3.0  kg / m2,年龄:71年 ± 3 y)进行评估,并进行了最大增量循环试验。肥胖组（43.1 ± 8.0）与非肥胖组（51.4 ± 11.1）相比，V (E) /V （CO2）斜率较低（43.1 ± 8.0）。虽然EELV在那些低(52.4 ±6.1  % TLC)与没有肥胖(58.9 ±5.8  % TLC), EILV相似(与肥胖:88.2 ± 4.5 vs没有肥胖: 89.2±4.2  % TLC)之间的组。肥胖患者的EELV从休息到运动高峰增加更多（0.23 ± 0.30 L vs. - 0.1 ± 0.4 L）。我们的研究结果表明，肥胖老年人对剧烈运动的通气反应减弱，这似乎与EILV增加侵犯TLC有关。

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引用次数: 0

The role of the midbrain tegmentum in the regulation of breathing patterns in carp (Cyprinus carpio) and trout (Onchorhynchus mykiss) 中脑被盖在鲤鱼和鳟鱼呼吸模式调节中的作用。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-04 DOI: 10.1016/j.resp.2025.104487

O.’Neill Angela E., Lumsden Amanda L. , Milsom William K.

In vertebrates, the basic respiratory rhythm is modified by both sensory feedback and input from higher centers to produce a broad range of breathing patterns. In carp (Cyprinus carpio L.), breathing is often episodic while in trout (Onchorhynchus mykiss) it is continuous and rhythmic except when water is hyperoxic. A previous study in carp revealed that stimulation of neurons at a site in the dorsal mesencephalic tegmentum (DMT) ventrolateral to the oculomotor nucleus, can terminate the apneas and initiate breathing episodes (Juch and Ballintijn, 1983). Such stimulation, however, did not eliminate the apneas or the breathing episodes. To determine whether this site also contains neurons involved in initiating periods of apnea that are intrinsic to episodic breathing, we attempted to lesion the DMT site in decerebrate, spinalectomized carp and trout using stereotaxic microinjections of 0.01 mM kainic acid. Following decerebration and spinalectomy, 93 % of carp and 33 % of trout breathed in episodes in hyperoxic water. Kainic acid injections initially stimulated breathing in all fish. As the excitotoxic effects progressed, breathing frequency and breath amplitude returned to normal levels suggesting that sites within the areas we lesioned are not involved in establishing the overall level of respiratory drive. The ensuing lesions, however, eliminated the episodic breathing in hyperoxia in over 50 % of the carp and 33 % of the trout. This suggests that sites within the midbrain tegmentum are involved in establishing breathing patterns and that there is a non-uniform distribution of neurons within the midbrain tegmentum involved in producing apneas and clustering breaths into episodes.

在脊椎动物中，基本的呼吸节奏被感觉反馈和来自更高中枢的输入所修改，从而产生范围广泛的呼吸模式。鲤鱼（Cyprinus carpio L.）的呼吸通常是断断续续的，而鳟鱼（Onchorhynchus mykiss）的呼吸是连续的和有节奏的，除非水是高氧的。先前对鲤鱼的一项研究表明，刺激动眼核腹侧的中脑背被（DMT）的一个部位的神经元，可以终止呼吸暂停并引发呼吸发作（Juch和Ballintijn， 1983）。然而，这种刺激并不能消除呼吸暂停或呼吸发作。为了确定该部位是否也包含与间歇性呼吸所固有的呼吸暂停启动期有关的神经元，我们尝试用立体定向显微注射0.01mM的kainic酸来损伤去脑、去脊髓的鲤鱼和鳟鱼的DMT部位。在去脑和脊柱切除后，93%的鲤鱼和33%的鳟鱼在高氧水中发作呼吸。Kainic酸注射最初刺激了所有鱼的呼吸。随着兴奋性毒性作用的进展，呼吸频率和呼吸幅度恢复到正常水平，这表明我们损伤的区域内的部位不参与建立呼吸驱动的总体水平。然而，随后的损伤消除了50%以上的鲤鱼和33%的鳟鱼的间歇性高氧呼吸。这表明中脑被盖内的部位参与了呼吸模式的建立，中脑被盖内的神经元分布不均匀，参与了呼吸暂停的产生和呼吸聚集成几次。

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引用次数: 0

Therapeutic acute intermittent hypoxia modestly improves breathing in Pompe disease 急性间歇缺氧治疗可适度改善庞贝病患者的呼吸。

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-09 DOI: 10.1016/j.resp.2025.104489

Angela L. Roger , Meredith L. Huston , Madison Spaulding , Caroline M. Metz , Ryan Froeb , Raechel Wu , Sean Kehoe , Gordon S. Mitchell , Mai K. ElMallah

Pompe disease is an autosomal recessive neuromuscular disorder characterized by a deficiency of acid α-glucosidase (GAA), an enzyme responsible for lysosomal glycogen degradation in all cells. Respiratory distress is a common symptom among patients with Pompe disease resulting from weakness of primary respiratory neuromuscular units of the diaphragm and genioglossus and the motor neurons which innervate them. The only FDA approved treatment is enzyme replacement therapy (ERT) of recombinant human GAA (rhGAA) which slows the decline of motor function and extends life expectancy. However, ERT does not cross the blood-brain barrier and thus, is unable to treat the critical pathology present in motor neurons hindering long-term efficacy. In the present study, we sought to explore an alternative treatment for Pompe patients to improve breathing by improving the function of motor neurons. Therapeutic acute intermittent hypoxia (tAIH) is a non-invasive therapeutic modality which has had success in improving respiratory and non-respiratory motor function in patients with spinal cord injury, amyotrophic lateral sclerosis, multiple sclerosis, and stroke. Here, we treated adult Gaa^-/- mice with a single, week-long tAIH protocol, followed by bi-weekly tAIH for 4 months. We report three critical findings: (1) both short and long-term tAIH therapy modestly improve breathing in Gaa^-/- mice; (2) long-term tAIH-therapy in WT mice moderately elevates breathing responses; and (3) these trending improvements to respiration in Gaa^-/- may be related to changes in chemoreflex activation, reduced kyphosis, and improved overlap of acetylcholine receptors and phrenic motor neuron axon terminals in the diaphragm muscle.

庞贝病是一种常染色体隐性神经肌肉疾病，其特征是缺乏酸性α-葡萄糖苷酶（GAA），一种在所有细胞中负责溶酶体糖原降解的酶。呼吸窘迫是庞贝病患者的常见症状，由膈肌和颏舌肌的初级呼吸神经肌肉单位以及支配它们的运动神经元无力引起。FDA唯一批准的治疗方法是重组人GAA （rhGAA）的酶替代疗法（ERT），它减缓了运动功能的衰退，延长了预期寿命。然而，ERT不能穿过血脑屏障，因此不能治疗运动神经元中存在的阻碍长期疗效的关键病理。在本研究中，我们试图探索一种通过改善运动神经元功能来改善Pompe患者呼吸的替代治疗方法。治疗性急性间歇缺氧（tAIH）是一种非侵入性治疗方式，在改善脊髓损伤、肌萎缩侧索硬化症、多发性硬化症和中风患者的呼吸和非呼吸运动功能方面取得了成功。在这里，我们对成年Gaa-/-小鼠进行了为期一周的单次tAIH治疗，然后进行了为期4个月的双周tAIH治疗。我们报告了三个关键发现：(1)短期和长期tAIH治疗均可适度改善Gaa-/-小鼠的呼吸；(2)长期taih治疗可适度提高WT小鼠的呼吸反应；(3) Gaa-/-中呼吸的这些趋势改善可能与化学反射激活的变化、后凸的减少以及膈肌中乙酰胆碱受体和膈运动神经元轴突末端重叠的改善有关。

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引用次数: 0

Diaphragm pacing elicits respiratory plasticity in awake rodents after C2 hemisection 横膈膜起搏引起清醒啮齿动物C2半切后的呼吸可塑性

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-01 Epub Date: 2025-08-23 DOI: 10.1016/j.resp.2025.104485

Taylor C. Holmes, Kaylyn A. Schwichtenberg, Kristi A. Streeter

Cervical spinal cord injury (cSCI) creates profound respiratory deficits that are commonly managed with chronic mechanical ventilation. Diaphragm pacing (DP) is an emerging clinical intervention designed to combat the deleterious effects associated with chronic mechanical ventilation. While anecdotal evidence suggests that DP may restore independent breathing, the impact of daily DP on respiratory output is unknown. Therefore, we investigated if DP induces ventilatory and diaphragm electromyography (EMG) plasticity in awake rodents following cSCI. All animals (n = 42) were implanted with diaphragm EMGs, received a left incomplete C2 hemisection, and were treated with DP, DP + dorsal rhizotomy, or served as controls (no DP). In animals receiving a dorsal rhizotomy, the left cervical dorsal roots (C4-C6) were cut to test if phrenic afferents are necessary for the induction of plasticity. One week after C2 hemisection, we delivered daily DP for 1 h/day (5 min on/5 min off) and recorded ventilation and diaphragm EMG output for 60 min over 4 consecutive days. During DP, we found an increase in tidal volume. After DP, tidal volume remained elevated in males for at least 60 min, and to a lesser extent in females. DP increased diaphragm EMG amplitude 60 min post-pacing in males, but not females. Despite an identical DP intervention, rhizotomy treated male animals did not exhibit a sustained increase in tidal volume or EMG amplitude. Our data suggests that DP induces phrenic afferent dependent plasticity characterized by a long-lasting increase in tidal volume and diaphragm EMG amplitude in awake male rodents following cSCI.

颈脊髓损伤（cSCI）造成严重的呼吸缺陷，通常通过慢性机械通气进行治疗。隔膜起搏（DP）是一种新兴的临床干预措施，旨在对抗与慢性机械通气相关的有害影响。虽然坊间证据表明，DP可以恢复独立呼吸，但每日DP对呼吸输出量的影响尚不清楚。因此，我们研究了DP是否会诱导cSCI后清醒啮齿动物的通气和膈肌电图（EMG）可塑性。所有动物（n = 42）植入膈肌肌电图，接受左C2半切断术，DP、DP + 背根切断术治疗，或作为对照组（未DP）。在接受背根切开术的动物中，左颈背根（C4-C6）被切断，以测试颅传入神经是否对可塑性的诱导是必要的。C2半切一周后，我们每天进行1 h/天的DP（5 min开/5 min关），并连续4天记录通气和膈肌肌电输出60 min。DP期间，我们发现潮汐量增加。DP后，男性潮气量升高至少60 min，女性潮气量升高程度较小。DP增加男性起搏后膈肌肌电振幅60 min，而女性没有。尽管进行了相同的DP干预，根切断术治疗的雄性动物并没有表现出潮汐量或肌电图振幅的持续增加。我们的数据表明，DP诱导膈传入依赖的可塑性，其特征是cSCI后醒着的雄性啮齿动物的潮汐量和膈肌肌电图振幅的持续增加。

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引用次数: 0

Eupneic respiratory pattern and ventilatory responses to environmental CO2 in a small lizard, Anolis carolinensis 小蜥蜴卡罗莱纳蜥蜴的呼吸模式和对环境CO2的通气反应

IF 1.6 4区医学 Q3 PHYSIOLOGY

Respiratory Physiology & Neurobiology

Pub Date : 2025-11-01 Epub Date: 2025-09-02 DOI: 10.1016/j.resp.2025.104486

Ryan W. Bavis, Devin Russell, Mary Buford Turnage , Andrew M. Mountcastle

Lizards and other reptiles are generally described as breathing intermittently, either with single breaths separated by variable periods of apnea or with clusters of breaths separated by prolonged apneas (i.e., episodic breathing). However, relatively little is known about the breathing of small lizards (≤ 10 g) even though the average body mass of extant species is only 8 g. Accordingly, head-body plethysmography was used to assess breathing in the green anole (Anolis carolinensis). Ventilation was measured in adult anoles (2 – 6 g) while exposed to room air (0 % CO₂) and hypercarbic gas mixtures (1 %, 3 %, and 5 % CO₂), and during recovery from hypercarbia. A. carolinensis exhibited a continuous, rhythmic breathing pattern in room air with most (90 %) breaths lacking any discernible end-inspiratory pause; apneas were infrequent (1.3 ± 0.2 apneas per 5 min (mean±SEM; n = 16)). Minute ventilation increased during exposures to 1 % and 5 % CO₂ largely through increases in tidal volume, but the response to 3 % CO₂ was variable due to the emergence of end-inspiratory pauses each respiratory cycle (and concomitant slowing of respiratory frequency) during the 3 % and 5 % CO₂ exposures. A marked post-hypercarbic hyperpnea was observed during the return to 0 % CO₂, the magnitude of which increased with the severity of the hypercarbic challenge. Although the ventilatory responses to CO₂ and post-hypercarbic hyperpnea are consistent with reports for other reptile species, these data highlight that the classic description of intermittent breathing in reptiles may not apply to all small lizards, perhaps due to their higher mass-specific metabolic demands.

蜥蜴和其他爬行动物通常被描述为间歇性呼吸，要么是单次呼吸被不同时期的呼吸暂停分开，要么是长时间的呼吸暂停（即，间歇呼吸）。然而，对小型蜥蜴（≤10 g）的呼吸知之甚少，尽管现存物种的平均体重只有8 g。因此，头-体体积脉搏描记术被用来评估绿蜥（卡洛林斑蜥）的呼吸。在暴露于室内空气（0 % CO2）和高碳化气体混合物（1 %，3 %和5 % CO2）以及高碳化恢复期间，测量成虫（2 - 6 g）的通风量。卡罗林娜在室内空气中表现出连续的、有节奏的呼吸模式，大多数（90% %）呼吸没有任何明显的吸气末暂停；呼吸暂停不常见（1.3 ± 0.2次呼吸暂停/ 5 min（平均值±SEM； n = 16））。在暴露于1 %和5 % CO2时，微小通气量增加主要是由于潮气量的增加，但在3 %和5 % CO2暴露期间，由于每个呼吸周期出现吸气末暂停（以及伴随的呼吸频率减慢），对3 % CO2的响应是可变的。在返回0 % CO2时观察到明显的高碳后呼吸急促，其程度随着高碳挑战的严重程度而增加。尽管对二氧化碳和高碳后呼吸急促的通气反应与其他爬行动物物种的报道一致，但这些数据强调，爬行动物间歇性呼吸的经典描述可能并不适用于所有小蜥蜴，这可能是由于它们更高的质量特异性代谢需求。

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引用次数: 0