Pub Date : 2024-11-12DOI: 10.1016/j.resp.2024.104368
Yilun Liu , Jiana Li , Rongchang Chen , Fei Shi , Yi Xiong
Asthma is a common chronic inflammatory airway disease, imposing a substantial health and economic burden on society and individuals. Current treatments primarily focus on symptom relief and lung function improvement, often failing to address the underlying pathology. Thus, exploring new therapeutic approaches is crucial. Airway smooth muscle cells (ASMCs) play a key role in regulating airway tone and airflow, while abnormal ASMCs proliferation contributes to airway remodeling in asthma. Airway epithelial cells (AECs), serving as the first barrier against pathogens and allergens, also have critical immune functions.
This study focuses on the interaction between AECs and ASMCs, as AECs are more accessible for drug delivery due to their location at the airway surface. Investigating this relationship could facilitate novel interventions targeting AECs to inhibit pathological ASMCs activity. In our experiment, we isolated ASMCs and AECs from healthy mice and found that AECs significantly promoted ASMCs proliferation in co-culture. RNA sequencing revealed that this process might be linked to the activation of the canonical Wnt signaling pathway in ASMCs. By using Wnt pathway inhibitors (endo-IWR1) and siRNA to disrupt Wnt receptors, we reversed this phenotype. This finding suggests that AECs may promote ASMCs proliferation by activating the Wnt pathway in ASMCs. The Wnt/β-catenin pathway appears to play an important role in ASMCs proliferation, indicating that future pathological studies should consider the potential involvement of the Wnt pathway in airway remodeling.
{"title":"Airway epithelial cells promote in vitro airway smooth muscle cell proliferation by activating the Wnt/β-catenin pathway","authors":"Yilun Liu , Jiana Li , Rongchang Chen , Fei Shi , Yi Xiong","doi":"10.1016/j.resp.2024.104368","DOIUrl":"10.1016/j.resp.2024.104368","url":null,"abstract":"<div><div>Asthma is a common chronic inflammatory airway disease, imposing a substantial health and economic burden on society and individuals. Current treatments primarily focus on symptom relief and lung function improvement, often failing to address the underlying pathology. Thus, exploring new therapeutic approaches is crucial. Airway smooth muscle cells (ASMCs) play a key role in regulating airway tone and airflow, while abnormal ASMCs proliferation contributes to airway remodeling in asthma. Airway epithelial cells (AECs), serving as the first barrier against pathogens and allergens, also have critical immune functions.</div><div>This study focuses on the interaction between AECs and ASMCs, as AECs are more accessible for drug delivery due to their location at the airway surface. Investigating this relationship could facilitate novel interventions targeting AECs to inhibit pathological ASMCs activity. In our experiment, we isolated ASMCs and AECs from healthy mice and found that AECs significantly promoted ASMCs proliferation in co-culture. RNA sequencing revealed that this process might be linked to the activation of the canonical Wnt signaling pathway in ASMCs. By using Wnt pathway inhibitors (endo-IWR1) and siRNA to disrupt Wnt receptors, we reversed this phenotype. This finding suggests that AECs may promote ASMCs proliferation by activating the Wnt pathway in ASMCs. The Wnt/β-catenin pathway appears to play an important role in ASMCs proliferation, indicating that future pathological studies should consider the potential involvement of the Wnt pathway in airway remodeling.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104368"},"PeriodicalIF":1.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627112","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 : 2024-11-10DOI: 10.1016/j.resp.2024.104367
Marcel Veternik , Michal Simera , Lukas Martvon , Lucia Cibulkova , Zuzana Kotmanova , Ivan Poliacek
The relationship between the level (rate) of stimulus and the characteristics of the cough response was studied on 15 spontaneously breathing anesthetized cats. Three modes of stimulation were used to elicit cough. ‘High’ vs. ‘low’ level of stimulation was accomplished: 1st mode by 1 vs. 4 penetrations of the soft catheter through the trachea (approximately 10 cm), 2nd mode by 2 penetrations with the soft catheter equipped with 4 fine cross nylon fibers vs. 4 penetrations by the stimulator with 8 fibers, and 3rd mode by a similar stimulator with 4 cross fibers probing 4 cm of the trachea either right below the larynx or deeper under the upper part of the sternum (data were pooled) vs. stimulating both areas at the same time. ‘High’ stimulation rate in each stimulation mode resulted in a higher number of coughs, increased cough efforts, and shortened several temporal cough features. Mechanical stimulation resulting in higher cough afferent drive induces more vigorous coughing with shorter temporal cough characteristics. Modulation of cough afferent input affects both spatial and temporal components of the cough motor pattern, representing a crucial point in cough management.
{"title":"Effect of various modes of tracheal mechanical stimulation on the cough motor pattern","authors":"Marcel Veternik , Michal Simera , Lukas Martvon , Lucia Cibulkova , Zuzana Kotmanova , Ivan Poliacek","doi":"10.1016/j.resp.2024.104367","DOIUrl":"10.1016/j.resp.2024.104367","url":null,"abstract":"<div><div>The relationship between the level (rate) of stimulus and the characteristics of the cough response was studied on 15 spontaneously breathing anesthetized cats. Three modes of stimulation were used to elicit cough. ‘High’ vs. ‘low’ level of stimulation was accomplished: 1st mode by 1 vs. 4 penetrations of the soft catheter through the trachea (approximately 10 cm), 2nd mode by 2 penetrations with the soft catheter equipped with 4 fine cross nylon fibers vs. 4 penetrations by the stimulator with 8 fibers, and 3rd mode by a similar stimulator with 4 cross fibers probing 4 cm of the trachea either right below the larynx or deeper under the upper part of the sternum (data were pooled) vs. stimulating both areas at the same time. ‘High’ stimulation rate in each stimulation mode resulted in a higher number of coughs, increased cough efforts, and shortened several temporal cough features. Mechanical stimulation resulting in higher cough afferent drive induces more vigorous coughing with shorter temporal cough characteristics. Modulation of cough afferent input affects both spatial and temporal components of the cough motor pattern, representing a crucial point in cough management.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"332 ","pages":"Article 104367"},"PeriodicalIF":1.9,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142627113","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 : 2024-11-06DOI: 10.1016/j.resp.2024.104363
Diana Andrea Arias Fernández , Héctor Alfonso Romero Diaz , Alan David Figueroa Garnica , Pablo Iturri-Soliz , Christian Arias-Reyes , Edith Mariane Schneider Gasser , Jorge Soliz
In addition to its hematopoietic function, erythropoietin (EPO) has demonstrated neuroprotective properties in preclinical studies, particularly in cases of reduced oxygenation or ischemia in the neonatal brain. While these findings have sparked optimism for its potential clinical application, the efficacy of EPO remains contentious in translational assays. Notably, while repeated administration of low doses of EPO has correlated with a decrease in adverse outcomes, the use of high EPO doses has shown either negligible or potentially detrimental effects on the incidence of brain injury. In this pilot study, we explored the effects of low and sustained doses of EPO (400 IU/kg) on the incidence of intraventricular hemorrhage (IVH) in premature infants. EPO was administered intravenously three times a week until the infants reached 32 weeks corrected gestational age. Our results indicate a significant decrease in the incidence of IVH with EPO treatment. Although, this study does not provide conclusive evidence on EPO's ability to reverse established IVH, these results strongly support the need for larger-scale clinical trials to further assess EPO's therapeutic potential.
{"title":"Low and sustained doses of erythropoietin prevent preterm infants from intraventricular hemorrhage","authors":"Diana Andrea Arias Fernández , Héctor Alfonso Romero Diaz , Alan David Figueroa Garnica , Pablo Iturri-Soliz , Christian Arias-Reyes , Edith Mariane Schneider Gasser , Jorge Soliz","doi":"10.1016/j.resp.2024.104363","DOIUrl":"10.1016/j.resp.2024.104363","url":null,"abstract":"<div><div>In addition to its hematopoietic function, erythropoietin (EPO) has demonstrated neuroprotective properties in preclinical studies, particularly in cases of reduced oxygenation or ischemia in the neonatal brain. While these findings have sparked optimism for its potential clinical application, the efficacy of EPO remains contentious in translational assays. Notably, while repeated administration of low doses of EPO has correlated with a decrease in adverse outcomes, the use of high EPO doses has shown either negligible or potentially detrimental effects on the incidence of brain injury. In this pilot study, we explored the effects of low and sustained doses of EPO (400 IU/kg) on the incidence of intraventricular hemorrhage (IVH) in premature infants. EPO was administered intravenously three times a week until the infants reached 32 weeks corrected gestational age. Our results indicate a significant decrease in the incidence of IVH with EPO treatment. Although, this study does not provide conclusive evidence on EPO's ability to reverse established IVH, these results strongly support the need for larger-scale clinical trials to further assess EPO's therapeutic potential.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104363"},"PeriodicalIF":1.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.1016/j.resp.2024.104365
Fang Liu , Alice Y.M. Jones , Raymond C.C. Tsang , Timothy T.T. Yam , William W.N. Tsang
Background
Inspiratory muscle training (IMT) is often employed to enhance improvement in inspiratory muscle strength. However, the relationship between inspiratory muscle recruitment patterns and increasing inspiratory load remains unclear. Furthermore, the effect of breathing instructions on diaphragm activity at various inspiratory loads is unknown.
Objective
To investigate the recruitment activity of the diaphragm and sternocleidomastoid (SCM) muscle under increased inspiratory pressure loading, with and without diaphragmatic breathing instructions, in healthy young adults.
Methods
Participants were invited to breathe, in random order, 6 sets of 10 breaths at inspiratory loads of 30 % to 80 % maximal inspiratory pressure (MIP), in 10 % increments. The measurement process was repeated with a specific focus of diaphragmatic descent during inspiration. During each targeted breath, recordings of surface electromyography of the right SCM muscle and thickness of the right hemi-diaphragm measured by ultrasonography were undertaken concurrently.
Results
Sixty-two adults (31 males, age: 23±3 years) participated in the study. Irrespective of breathing instructions, computed diaphragm thickening fraction (DTf) increased with increasing inspiratory load but peaked at 50 % MIP and declined with increasing load to 80 % MIP. SCM recruitment increased with increasing inspiratory load to 80 % MIP. Forced inspiration with diaphragmatic breathing was associated with a higher DTf and lower SCM muscle activity. The above pattern was similar for both male and female participants. Female participants produced higher SCM activity compared with males but only at inspiration loads below 50 % MIP.
Conclusions
In a cohort of young healthy adults, magnitude of diaphragmatic effort was greatest at 50 % MIP but declined with increasing inspiratory load to 80 % MIP. Forced inspiration combined with focused diaphragmatic breathing accentuated diaphragm contraction and reduced SCM muscle contribution. Our findings show that diaphragmatic muscle recruitment is non-linear and that the generic clinical prescription of an IMT program may need to be reconfigured.
{"title":"Recruitment of the diaphragm and sternocleidomastoid muscle during increasing inspiratory pressure loads in healthy young adults","authors":"Fang Liu , Alice Y.M. Jones , Raymond C.C. Tsang , Timothy T.T. Yam , William W.N. Tsang","doi":"10.1016/j.resp.2024.104365","DOIUrl":"10.1016/j.resp.2024.104365","url":null,"abstract":"<div><h3>Background</h3><div>Inspiratory muscle training (IMT) is often employed to enhance improvement in inspiratory muscle strength. However, the relationship between inspiratory muscle recruitment patterns and increasing inspiratory load remains unclear. Furthermore, the effect of breathing instructions on diaphragm activity at various inspiratory loads is unknown.</div></div><div><h3>Objective</h3><div>To investigate the recruitment activity of the diaphragm and sternocleidomastoid (SCM) muscle under increased inspiratory pressure loading, with and without diaphragmatic breathing instructions, in healthy young adults.</div></div><div><h3>Methods</h3><div>Participants were invited to breathe, in random order, 6 sets of 10 breaths at inspiratory loads of 30 % to 80 % maximal inspiratory pressure (MIP), in 10 % increments. The measurement process was repeated with a specific focus of diaphragmatic descent during inspiration. During each targeted breath, recordings of surface electromyography of the right SCM muscle and thickness of the right hemi-diaphragm measured by ultrasonography were undertaken concurrently.</div></div><div><h3>Results</h3><div>Sixty-two adults (31 males, age: 23±3 years) participated in the study. Irrespective of breathing instructions, computed diaphragm thickening fraction (DTf) increased with increasing inspiratory load but peaked at 50 % MIP and declined with increasing load to 80 % MIP. SCM recruitment increased with increasing inspiratory load to 80 % MIP. Forced inspiration with diaphragmatic breathing was associated with a higher DTf and lower SCM muscle activity. The above pattern was similar for both male and female participants. Female participants produced higher SCM activity compared with males but only at inspiration loads below 50 % MIP.</div></div><div><h3>Conclusions</h3><div>In a cohort of young healthy adults, magnitude of diaphragmatic effort was greatest at 50 % MIP but declined with increasing inspiratory load to 80 % MIP. Forced inspiration combined with focused diaphragmatic breathing accentuated diaphragm contraction and reduced SCM muscle contribution. Our findings show that diaphragmatic muscle recruitment is non-linear and that the generic clinical prescription of an IMT program may need to be reconfigured.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104365"},"PeriodicalIF":1.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569288","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 : 2024-10-29DOI: 10.1016/j.resp.2024.104364
Sabino Guglielmini , Elena Wiggli , Felix Scholkmann , Martin Wolf
Significance
Cerebral blood flow is influenced by respiration, primarily through changes in the CO2 concentration of arterial blood.
Aim
The objective of this study was to investigate the effect of changes in arterial CO2 concentration induced by respiratory changes on oxygenation and hemodynamics in the cerebral and extracerebral tissue layers of the forehead.
Approach
We used systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) to assess changes in forehead hemodynamics and oxygenation as well as systemic physiology in 20 healthy subjects. All participants performed two respiratory tasks (breath-holding and hyperventilation).
Results
In our SPA-fNIRS study we found that changes in breathing affected hemodynamics and oxygenation in both the extracerebral and cerebral tissue layers of the forehead in characteristic ways, depending on the two respiratory tasks.
Conclusion
The results show that extracerebrovascular reactivity (ECVR) exists in parallel with the well-known cerebrovascular reactivity (CVR). CVR and ECVR must be considered when performing fNIRS neuroimaging studies involving changes in respiration.
{"title":"Hemodynamics and vascular oxygenation measured at the forehead during changes in respiration: A SPA-fNIRS study","authors":"Sabino Guglielmini , Elena Wiggli , Felix Scholkmann , Martin Wolf","doi":"10.1016/j.resp.2024.104364","DOIUrl":"10.1016/j.resp.2024.104364","url":null,"abstract":"<div><h3>Significance</h3><div>Cerebral blood flow is influenced by respiration, primarily through changes in the CO<sub>2</sub> concentration of arterial blood.</div></div><div><h3>Aim</h3><div>The objective of this study was to investigate the effect of changes in arterial CO<sub>2</sub> concentration induced by respiratory changes on oxygenation and hemodynamics in the cerebral and extracerebral tissue layers of the forehead.</div></div><div><h3>Approach</h3><div>We used systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) to assess changes in forehead hemodynamics and oxygenation as well as systemic physiology in 20 healthy subjects. All participants performed two respiratory tasks (breath-holding and hyperventilation).</div></div><div><h3>Results</h3><div>In our SPA-fNIRS study we found that changes in breathing affected hemodynamics and oxygenation in both the extracerebral and cerebral tissue layers of the forehead in characteristic ways, depending on the two respiratory tasks.</div></div><div><h3>Conclusion</h3><div>The results show that extracerebrovascular reactivity (ECVR) exists in parallel with the well-known cerebrovascular reactivity (CVR). CVR and ECVR must be considered when performing fNIRS neuroimaging studies involving changes in respiration.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104364"},"PeriodicalIF":1.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.resp.2024.104362
Chiara Gattoni, Asghar Abbasi, Carrie Ferguson, Charles W. Lanks, Thomas W. Decato, Harry B. Rossiter, Richard Casaburi, William W. Stringer
Background
Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients.
Methods
15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; BMI = 32.2(8.5) kg/m2] performed a pulmonary function test and two ramp-incremental CPETs separated by 24 hr. CPET variables included gas exchange threshold (GET), peak oxygen uptake (O2peak) and peak work rate (WRpeak). Ratings of perceived dyspnoea and leg effort were recorded at peak exercise using the modified 0–10 Borg Scale. PEM (past six months) was assessed using the modified DePaul Symptom Questionnaire (mDSQ). One-sample t-tests were used to test significance of mean difference between days (p<0.05).
Results.
mDSQ revealed PEM in 80 % of patients. Lung function was normal. Responses to day 1 CPET were consistent with the presence of aerobic deconditioning in 40 % of patients (O2peak <80 % predicted, in the absence of evidence of cardiovascular and pulmonary limitations). There were no differences between day-1 and day-2 CPET responses (all p>0.05).
Conclusion
PEM symptoms in Long COVID patients, in the absence of differences in two-day CPET responses separated by 24 hours, suggests that PEM is not due to impaired recovery of exercise capacity between days.
{"title":"Two-day cardiopulmonary exercise testing in long COVID post-exertional malaise diagnosis","authors":"Chiara Gattoni, Asghar Abbasi, Carrie Ferguson, Charles W. Lanks, Thomas W. Decato, Harry B. Rossiter, Richard Casaburi, William W. Stringer","doi":"10.1016/j.resp.2024.104362","DOIUrl":"10.1016/j.resp.2024.104362","url":null,"abstract":"<div><h3>Background</h3><div>Long COVID patients present with a myriad of symptoms that can include fatigue, exercise intolerance and post exertional malaise (PEM). Long COVID has been compared to other post viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), where a reduction in day 2 cardiopulmonary exercise test (CPET) performance of a two-day CPET protocol is suggested to be a result of PEM. We investigated cardiopulmonary and perceptual responses to a two-day CPET protocol in Long COVID patients.</div></div><div><h3>Methods</h3><div>15 Long COVID patients [n=7 females; mean (SD) age: 53(11) yr; BMI = 32.2(8.5) kg/m<sup>2</sup>] performed a pulmonary function test and two ramp-incremental CPETs separated by 24 hr. CPET variables included gas exchange threshold (GET), peak oxygen uptake (<span><math><mrow><mover><mrow><mi>V</mi></mrow><mrow><mo>̇</mo></mrow></mover></mrow></math></span>O<sub>2peak</sub>) and peak work rate (W<em>R</em><sub>peak</sub>). Ratings of perceived dyspnoea and leg effort were recorded at peak exercise using the modified 0–10 Borg Scale. PEM (past six months) was assessed using the modified DePaul Symptom Questionnaire (mDSQ). One-sample <em>t</em>-tests were used to test significance of mean difference between days (p<0.05).</div></div><div><h3>Results.</h3><div>mDSQ revealed PEM in 80 % of patients. Lung function was normal. Responses to day 1 CPET were consistent with the presence of aerobic deconditioning in 40 % of patients (<span><math><mrow><mover><mrow><mi>V</mi></mrow><mrow><mo>̇</mo></mrow></mover></mrow></math></span>O<sub>2peak</sub> <80 % predicted, in the absence of evidence of cardiovascular and pulmonary limitations). There were no differences between day-1 and day-2 CPET responses (all p>0.05).</div></div><div><h3>Conclusion</h3><div>PEM symptoms in Long COVID patients, in the absence of differences in two-day CPET responses separated by 24 hours, suggests that PEM is not due to impaired recovery of exercise capacity between days.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104362"},"PeriodicalIF":1.9,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-19DOI: 10.1016/j.resp.2024.104361
Pedro Alves Machado-Junior , Marcelo Santiago Soares Dias , Ana Beatriz Farias de Souza , Leonardo Spinelli Estevão Lopes , Tatiana Prata Menezes , André Talvani , Laurent Brochard , Frank Silva Bezerra
Background
Mechanical ventilation (MV) is a life support method used to treat patients with respiratory failure. High tidal volumes during MV can cause ventilator-induced lung injury (VILI), but also affect other organs, such as the diaphragm (Dia) causing ventilator-induced diaphragmatic dysfunction (VIDD). VIDD is often associated with a complicated course on MV. Sepsis can induce inflammation and oxidative stress, contributing to the impairment of the Dia and worsening of the prognosis. This study evaluated the additive or synergistic effects of a short course of mechanical ventilation on Dia in healthy and septic adult mice.
Methods
32 adult male C57BL/6 mice were randomly into four groups: Control (CG), non-ventilated animals instilled with saline solution (PBS1x); Lipopolysaccharide (LPS), non-ventilated animals instilled with PBS solution containing lipopolysaccharide; Mechanical Ventilation (MV) for 1 h, ventilated animals instilled with PBS solution; and Mechanical Ventilation and LPS (MV+LPS), ventilated animals instilled with PBS solution containing LPS. At the end of the experimental protocol, the animals were euthanized, then blood and diaphragm tissue samples were collected.
Results
Evaluation of leukocyte/blood parameters and diaphragm muscle showed that MV, LPS and the combination of both were able to increase neutrophil count, creatine kinase, inflammatory mediators and oxidative stress in all groups compared to the control. MV and sepsis combined had additive effects on inflammation and lipid peroxidation.
Conclusions
A short course of Mechanical ventilation promotes inflammation and oxidative stress and, its combination with sepsis further increases local and systemic inflammation.
背景：机械通气（MV）是一种用于治疗呼吸衰竭患者的生命支持方法。机械通气期间的高潮气量可导致呼吸机诱发肺损伤（VILI），但也会影响其他器官，如引起呼吸机诱发膈肌功能障碍（VIDD）的膈肌（Dia）。VIDD 通常与 MV 的复杂病程有关。脓毒症可诱发炎症和氧化应激，导致膈肌受损和预后恶化。本研究评估了短期机械通气对健康和脓毒症成年小鼠 Dia 的叠加或协同作用：方法：将32只成年雄性C57BL/6小鼠随机分为四组：对照组（CG），灌注生理盐水（PBS1x）的非通气动物；脂多糖组（LPS），灌注含有脂多糖的PBS溶液的非通气动物；机械通气1小时组（MV），灌注PBS溶液的通气动物；机械通气和LPS组（MV+LPS），灌注含有LPS的PBS溶液的通气动物。实验结束后，对动物实施安乐术，然后采集血液和膈肌组织样本：结果：对白细胞/血液参数和膈肌的评估表明，与对照组相比，中性粒细胞增多症、脓毒症和两者的结合能增加所有组的中性粒细胞计数、肌酸激酶、炎症介质和氧化应激。中压和脓毒症联合作用对炎症和脂质过氧化具有叠加效应：结论：短期机械通气会促进炎症和氧化应激，与败血症合并使用会进一步增加局部和全身炎症。
{"title":"A short duration of mechanical ventilation alters redox status in the diaphragm and aggravates inflammation in septic mice","authors":"Pedro Alves Machado-Junior , Marcelo Santiago Soares Dias , Ana Beatriz Farias de Souza , Leonardo Spinelli Estevão Lopes , Tatiana Prata Menezes , André Talvani , Laurent Brochard , Frank Silva Bezerra","doi":"10.1016/j.resp.2024.104361","DOIUrl":"10.1016/j.resp.2024.104361","url":null,"abstract":"<div><h3>Background</h3><div>Mechanical ventilation (MV) is a life support method used to treat patients with respiratory failure. High tidal volumes during MV can cause ventilator-induced lung injury (VILI), but also affect other organs, such as the diaphragm (Dia) causing ventilator-induced diaphragmatic dysfunction (VIDD). VIDD is often associated with a complicated course on MV. Sepsis can induce inflammation and oxidative stress, contributing to the impairment of the Dia and worsening of the prognosis. This study evaluated the additive or synergistic effects of a short course of mechanical ventilation on Dia in healthy and septic adult mice.</div></div><div><h3>Methods</h3><div>32 adult male C57BL/6 mice were randomly into four groups: Control (CG), non-ventilated animals instilled with saline solution (PBS1x); Lipopolysaccharide (LPS), non-ventilated animals instilled with PBS solution containing lipopolysaccharide; Mechanical Ventilation (MV) for 1 h, ventilated animals instilled with PBS solution; and Mechanical Ventilation and LPS (MV+LPS), ventilated animals instilled with PBS solution containing LPS. At the end of the experimental protocol, the animals were euthanized, then blood and diaphragm tissue samples were collected.</div></div><div><h3>Results</h3><div>Evaluation of leukocyte/blood parameters and diaphragm muscle showed that MV, LPS and the combination of both were able to increase neutrophil count, creatine kinase, inflammatory mediators and oxidative stress in all groups compared to the control. MV and sepsis combined had additive effects on inflammation and lipid peroxidation.</div></div><div><h3>Conclusions</h3><div>A short course of Mechanical ventilation promotes inflammation and oxidative stress and, its combination with sepsis further increases local and systemic inflammation.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104361"},"PeriodicalIF":1.9,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473463","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 : 2024-10-09DOI: 10.1016/j.resp.2024.104354
Ron Oliven , Arie Oliven , Mostafa Somri , Alan R. Schwartz , Emilia Hardak
Introduction
The genioglossus (GG) is known to be the main tongue protrusor, and therefore plays a major role in breathing. However, due to the fan shape of the GG fibers, it could be assumed that contraction of the anterior fibers of the GG do not cause tongue protrusion. In this study, we examined the effect of contraction of the anterior-vertical fibers of the GG (GGV) on the tongue and their EMG activity during wakefulness and sleep. The findings were compared to those of the longitudinal fibers (GGL), which, based on their orientation, are responsible for tongue protrusion.
Methods
Fine-wire electrode pairs were placed into the GGV and GGL in 11 patients with untreated OSA. Movement of the tongue during electrical stimulation at each site was videoed. The same electrodes were used to record EMG from both sites during respiratory stimulation by inspiratory loading and CO2 rebreathing during wakefulness. During sleep, repetitive flow limitation events were induced with low-level CPAP to augment GG activity.
Results
In all participants, electrical stimulation of GGL and GGV protruded and retracted the tongue, respectively. Respiratory stimulation increased GG activity, but GGV reached only 39 % and 23 % of peak GGL activity during high resistive loading and PCO2 of 65 mmHg, respectively. Flow limitation during sleep increased GGL to levels that were considerably higher than awake baseline, but GGV activity remained tonic or with minimal phasic activity, reaching on average 15 % of GGL peak activity.
Conclusions
Our electrical stimulation findings indicate that GGV is a tongue retractor and depressor. Tongue stimulation for OSA should avoid this area. The EMG results demonstrate that the anterior part of the GG is controlled very differently from the longitudinal protrusive fibers. The GGV responses are similar to those previously found in tongue retractors and peri-pharyngeal muscles other than the GG, in which diminished activation during sleep is likely to be involved in the failure of increasing GGL activity to alleviate flow limitation.
{"title":"Differential neuromotor control of the vertical and longitudinal genioglossus muscle fibers: An overlooked tongue retractor","authors":"Ron Oliven , Arie Oliven , Mostafa Somri , Alan R. Schwartz , Emilia Hardak","doi":"10.1016/j.resp.2024.104354","DOIUrl":"10.1016/j.resp.2024.104354","url":null,"abstract":"<div><h3>Introduction</h3><div>The genioglossus (GG) is known to be the main tongue protrusor, and therefore plays a major role in breathing. However, due to the fan shape of the GG fibers, it could be assumed that contraction of the anterior fibers of the GG do not cause tongue protrusion. In this study, we examined the effect of contraction of the anterior-vertical fibers of the GG (GG<sub>V</sub>) on the tongue and their EMG activity during wakefulness and sleep. The findings were compared to those of the longitudinal fibers (GG<sub>L</sub>), which, based on their orientation, are responsible for tongue protrusion.</div></div><div><h3>Methods</h3><div>Fine-wire electrode pairs were placed into the GG<sub>V</sub> and GG<sub>L</sub> in 11 patients with untreated OSA. Movement of the tongue during electrical stimulation at each site was videoed. The same electrodes were used to record EMG from both sites during respiratory stimulation by inspiratory loading and CO<sub>2</sub> rebreathing during wakefulness. During sleep, repetitive flow limitation events were induced with low-level CPAP to augment GG activity.</div></div><div><h3>Results</h3><div>In all participants, electrical stimulation of GG<sub>L</sub> and GG<sub>V</sub> protruded and retracted the tongue, respectively. Respiratory stimulation increased GG activity, but GG<sub>V</sub> reached only 39 % and 23 % of peak GG<sub>L</sub> activity during high resistive loading and PCO<sub>2</sub> of 65 mmHg, respectively. Flow limitation during sleep increased GG<sub>L</sub> to levels that were considerably higher than awake baseline, but GG<sub>V</sub> activity remained tonic or with minimal phasic activity, reaching on average 15 % of GG<sub>L</sub> peak activity.</div></div><div><h3>Conclusions</h3><div>Our electrical stimulation findings indicate that GG<sub>V</sub> is a tongue retractor and depressor. Tongue stimulation for OSA should avoid this area. The EMG results demonstrate that the anterior part of the GG is controlled very differently from the longitudinal protrusive fibers. The GG<sub>V</sub> responses are similar to those previously found in tongue retractors and peri-pharyngeal muscles other than the GG, in which diminished activation during sleep is likely to be involved in the failure of increasing GG<sub>L</sub> activity to alleviate flow limitation.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104354"},"PeriodicalIF":1.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401119","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 : 2024-10-09DOI: 10.1016/j.resp.2024.104359
Ricardo Gass , Franciele Plachi , Fernanda O.B. Silva , Talmir Nolasco , Mateus Samuel Tonetto , Leandro S. Goelzer , Paulo T. Muller , Marli M. Knorst , J. Alberto Neder , Danilo C. Berton
Excess exercise ventilation (high ventilation (V̇E)/carbon dioxide output (V̇CO2)) contributes significantly to dyspnea and exercise intolerance since the earlier stages of chronic obstructive pulmonary disease (COPD). A selective pulmonary vasodilator (inhaled nitric oxide) has shown to increase exercise tolerance secondary to lower V̇E/V̇CO2 and dyspnea in this patient population. We aimed to assess whether a clinically more practical option - oral sildenafil - would be associated with similar beneficial effects. In a randomized, placebo-controlled study, twenty-four patients with mild-to-moderate COPD completed, on different days, two incremental cardiopulmonary exercise tests (CPET) one hour after sildenafil or placebo. Eleven healthy participants performed a CPET in a non-interventional visit for comparative purposes with patients when receiving placebo. Patients (FEV1= 69.4 ± 13.5 % predicted) showed higher ventilatory demands (V̇E/V̇CO2), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV1= 98.3 ±11.6 % predicted). Contrary to our expectations, however, sildenafil (50 mg; N= 15) did not change exertional V̇E/V̇CO2, dead space/tidal volume ratio, operating lung volumes, dyspnea, or exercise tolerance compared to placebo (P>0.05). Due to the lack of significant beneficial effects, nine additional patients were trialed with a higher dose (100 mg). Similarly, active intervention was not associated with positive physiological or sensory effects. In conclusion, acute oral sildenafil (50 or 100 mg) failed to improve gas exchange efficiency or excess exercise ventilation in patients with predominantly moderate COPD. The current study does not endorse a therapeutic role for sildenafil to mitigate exertional dyspnea in this specific patient subpopulation.
{"title":"Effects of sildenafil on gas exchange, ventilatory, and sensory responses to exercise in subjects with mild-to-moderate COPD: A randomized cross-over trial","authors":"Ricardo Gass , Franciele Plachi , Fernanda O.B. Silva , Talmir Nolasco , Mateus Samuel Tonetto , Leandro S. Goelzer , Paulo T. Muller , Marli M. Knorst , J. Alberto Neder , Danilo C. Berton","doi":"10.1016/j.resp.2024.104359","DOIUrl":"10.1016/j.resp.2024.104359","url":null,"abstract":"<div><div>Excess exercise ventilation (high ventilation (V̇<sub>E</sub>)/carbon dioxide output (V̇CO<sub>2</sub>)) contributes significantly to dyspnea and exercise intolerance since the earlier stages of chronic obstructive pulmonary disease (COPD). A selective pulmonary vasodilator (inhaled nitric oxide) has shown to increase exercise tolerance secondary to lower V̇<sub>E</sub>/V̇CO<sub>2</sub> and dyspnea in this patient population. We aimed to assess whether a clinically more practical option - oral sildenafil - would be associated with similar beneficial effects. In a randomized, placebo-controlled study, twenty-four patients with mild-to-moderate COPD completed, on different days, two incremental cardiopulmonary exercise tests (CPET) one hour after sildenafil or placebo. Eleven healthy participants performed a CPET in a non-interventional visit for comparative purposes with patients when receiving placebo. Patients (FEV<sub>1</sub>= 69.4 ± 13.5 % predicted) showed higher ventilatory demands (V̇<sub>E</sub>/V̇CO<sub>2</sub>), worse pulmonary gas exchange, and higher dyspnea during exercise compared to controls (FEV<sub>1</sub>= 98.3 ±11.6 % predicted). Contrary to our expectations, however, sildenafil (50 mg; N= 15) did not change exertional V̇<sub>E</sub>/V̇CO<sub>2</sub>, dead space/tidal volume ratio, operating lung volumes, dyspnea, or exercise tolerance compared to placebo (<em>P</em>>0.05). Due to the lack of significant beneficial effects, nine additional patients were trialed with a higher dose (100 mg). Similarly, active intervention was not associated with positive physiological or sensory effects. In conclusion, acute oral sildenafil (50 or 100 mg) failed to improve gas exchange efficiency or excess exercise ventilation in patients with predominantly moderate COPD. The current study does not endorse a therapeutic role for sildenafil to mitigate exertional dyspnea in this specific patient subpopulation.</div><div>Clinical trial registry: <span><span>https://ensaiosclinicos.gov.br/rg/RBR-4qhkf4</span><svg><path></path></svg></span></div><div>Web of Science Researcher ID: O-7665–2019</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104359"},"PeriodicalIF":1.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401120","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}
Post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are debilitating post-viral conditions with many symptomatic overlaps, including exercise intolerance and autonomic dysfunction. Both conditions are growing in prevalence, and effective safe treatment strategies must be investigated. We hypothesized that inspiratory muscle training (IMT) could be used in PASC and mild to moderate ME/CFS to mitigate symptoms, improve exercise capacity, and improve autonomic function. We recruited healthy controls (n=12; 10 women), people with PASC (n=9; 8 women), and people with mild to moderate ME/CFS (n=12; 10 women) to complete 8 weeks of IMT. This project was registered as a clinical trial (NCT05196529) with clinicaltrials.gov. After completion of IMT, all groups experienced improvements in inspiratory muscle pressure (p<0.001), 6-minute walk distance (p=0.002), resting heart rate (p=0.037), heart rate variability (p<0.05), and symptoms related to sleep (p=0.009). In the ME/CFS group only, after completion of IMT, there were additional improvements with regard to vascular function (p=0.001), secretomotor function (p=0.023), the total weighted score (p=0.005) of the COMPASS 31 autonomic questionnaire, and symptoms related to pain (p=0.016). We found that after 8 weeks of IMT, people with PASC and/or ME/CFS could see some overall improvements in their autonomic function and symptomology.
{"title":"Inspiratory muscle training improves autonomic function in myalgic encephalomyelitis/chronic fatigue syndrome and post-acute sequelae of SARS-CoV-2: A pilot study","authors":"Heather Edgell , Tania J. Pereira , Kathleen Kerr , Riina Bray , Farah Tabassum , Lauren Sergio , Smriti Badhwar","doi":"10.1016/j.resp.2024.104360","DOIUrl":"10.1016/j.resp.2024.104360","url":null,"abstract":"<div><div>Post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are debilitating post-viral conditions with many symptomatic overlaps, including exercise intolerance and autonomic dysfunction. Both conditions are growing in prevalence, and effective safe treatment strategies must be investigated. We hypothesized that inspiratory muscle training (IMT) could be used in PASC and mild to moderate ME/CFS to mitigate symptoms, improve exercise capacity, and improve autonomic function. We recruited healthy controls (n=12; 10 women), people with PASC (n=9; 8 women), and people with mild to moderate ME/CFS (n=12; 10 women) to complete 8 weeks of IMT. This project was registered as a clinical trial (NCT05196529) with clinicaltrials.gov. After completion of IMT, all groups experienced improvements in inspiratory muscle pressure (p<0.001), 6-minute walk distance (p=0.002), resting heart rate (p=0.037), heart rate variability (p<0.05), and symptoms related to sleep (p=0.009). In the ME/CFS group only, after completion of IMT, there were additional improvements with regard to vascular function (p=0.001), secretomotor function (p=0.023), the total weighted score (p=0.005) of the COMPASS 31 autonomic questionnaire, and symptoms related to pain (p=0.016). We found that after 8 weeks of IMT, people with PASC and/or ME/CFS could see some overall improvements in their autonomic function and symptomology.</div></div>","PeriodicalId":20961,"journal":{"name":"Respiratory Physiology & Neurobiology","volume":"331 ","pages":"Article 104360"},"PeriodicalIF":1.9,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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