Pub Date : 2026-01-19DOI: 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.
{"title":"Tongue blade neuromuscular junction defects in old F344 rats","authors":"John F. Kemp , Gary C. Sieck , Matthew J. Fogarty","doi":"10.1016/j.resp.2026.104545","DOIUrl":"10.1016/j.resp.2026.104545","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104545"},"PeriodicalIF":1.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019580","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}
The essential role of upper airway muscles in maintaining patency has led to the hypothesis that alterations in tongue muscle properties may contribute to the development of obstructive sleep apnea (OSA). Prior studies comparing the mechanical characteristics of tongue muscles in OSA patients and healthy controls have yielded inconsistent results. In this study, we evaluated tongue muscle mechanics using an objective, non-volitional method: surface electrical stimulation of the genioglossus (GG) muscle. Tongue protrusion force, whether generated volitionally or by electrical stimulation, was significantly lower in OSA patients. Stimulated force was consistently lower than volitional force across all participants; however, the two measures were strongly correlated (r = 0.62, p < 0.001). Tongue muscle fatigability in OSA patients did not differ significantly from controls during volitional testing or low-frequency stimulation but was increased during high-frequency stimulation. Twitch contraction and half-relaxation times, as well as high-to-low frequency force curves, were comparable between OSA and control subjects. These findings indicate that although tongue muscle fiber composition appears similar in OSA and control groups, maximal tongue protrusion force is reduced in OSA. Given the inconsistent results of prior studies, we suggest that the methodology of force assessment may be critical: different testing modes likely recruit distinct patterns of tongue muscle coordination and may uncover coordination deficits in OSA. Furthermore, the increased fatigability observed during high-frequency stimulation is consistent with the presence of tongue muscle neuropathy in this population.
上气道肌肉在维持气道通畅方面的重要作用使得舌肌特性的改变可能导致阻塞性睡眠呼吸暂停（OSA）的发生。先前的研究比较了OSA患者和健康对照者舌肌的力学特性，结果并不一致。在这项研究中，我们评估舌肌力学使用客观的，非意志的方法：颏舌肌（GG）的表面电刺激。在OSA患者中，无论是自愿还是电刺激产生的舌突力都明显降低。在所有参与者中，受刺激的力量始终低于意志力量；然而，这两种测量结果是强相关的（r = 0.62, p < 0.001）。在意志测试或低频刺激时，OSA患者的舌肌疲劳与对照组无显著差异，但在高频刺激时，舌肌疲劳有所增加。抽搐收缩和半松弛时间以及高低频力曲线在OSA和对照组之间具有可比性。这些发现表明，尽管OSA组和对照组的舌肌纤维组成相似，但OSA组的最大舌突力有所降低。鉴于之前的研究结果不一致，我们认为力评估的方法可能是至关重要的：不同的测试模式可能会招募不同的舌肌协调模式，并可能发现OSA的协调缺陷。此外，在高频刺激期间观察到的疲劳增加与该人群中舌肌神经病变的存在是一致的。
{"title":"Neurophysiologic tongue protrusion characteristics$ in obstructive sleep apnea: A comparative study","authors":"Ron Oliven , Arie Oliven , Mostafa Somri , Emilia Hardak , Naveh Tov","doi":"10.1016/j.resp.2026.104544","DOIUrl":"10.1016/j.resp.2026.104544","url":null,"abstract":"<div><div>The essential role of upper airway muscles in maintaining patency has led to the hypothesis that alterations in tongue muscle properties may contribute to the development of obstructive sleep apnea (OSA). Prior studies comparing the mechanical characteristics of tongue muscles in OSA patients and healthy controls have yielded inconsistent results. In this study, we evaluated tongue muscle mechanics using an objective, non-volitional method: surface electrical stimulation of the genioglossus (GG) muscle. Tongue protrusion force, whether generated volitionally or by electrical stimulation, was significantly lower in OSA patients. Stimulated force was consistently lower than volitional force across all participants; however, the two measures were strongly correlated (r = 0.62, p < 0.001). Tongue muscle fatigability in OSA patients did not differ significantly from controls during volitional testing or low-frequency stimulation but was increased during high-frequency stimulation. Twitch contraction and half-relaxation times, as well as high-to-low frequency force curves, were comparable between OSA and control subjects. These findings indicate that although tongue muscle fiber composition appears similar in OSA and control groups, maximal tongue protrusion force is reduced in OSA. Given the inconsistent results of prior studies, we suggest that the methodology of force assessment may be critical: different testing modes likely recruit distinct patterns of tongue muscle coordination and may uncover coordination deficits in OSA. Furthermore, the increased fatigability observed during high-frequency stimulation is consistent with the presence of tongue muscle neuropathy in this population.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104544"},"PeriodicalIF":1.6,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990159","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}
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 V̇E – V̇CO2 slope in HYPV and FLAT, and a lower VT/ V̇E 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。
{"title":"Description of three dysfunctional breathing patterns in post-COVID dyspnea","authors":"Ivan Guerreiro , Aurélien Bringard , Pascal Weber , Viva Leverington , Aileen Kharat , Léon Genecand , Anna Taboni , Frédéric Lador","doi":"10.1016/j.resp.2026.104543","DOIUrl":"10.1016/j.resp.2026.104543","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div></div><div><h3>Results</h3><div>Age, BMI, gender and peak O<sub>2</sub> uptake (V̇O<sub>2</sub>) were similar between patterns. Compared to normal pattern (N), we found higher V̇<sub>E</sub> – V̇CO<sub>2</sub> slope in HYPV and FLAT, and a lower VT/ V̇<sub>E</sub> 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104543"},"PeriodicalIF":1.6,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948845","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}
Pub Date : 2026-01-05DOI: 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。
{"title":"Effect of superior laryngeal nerve stimulation on swallowing and respiratory coordination in dexmedetomidine-administered adult rats","authors":"Hinata Kubota, Ryoji Ide, Nana Sato Hashizume, Eishi Nakamura, Chikako Saiki","doi":"10.1016/j.resp.2026.104542","DOIUrl":"10.1016/j.resp.2026.104542","url":null,"abstract":"<div><div>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 α<sub>2</sub>-adrenoceptor/imidazoline I<sub>1</sub> receptor (α<sub>2</sub>AR/I<sub>1</sub>R) 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 (PaO<sub>2</sub>, PaCO<sub>2</sub>, 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.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"341 ","pages":"Article 104542"},"PeriodicalIF":1.6,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918367","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号