Alterations In Respiratory Function Research Articles

Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2 chemoreflex in rats

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2 chemosensitivity. Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targeting Phox2b mRNA, a reduction of PHOX2B expression was observed in Nmb neurons compared to both naive rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alter Nmb expression but it was associated with reduced expression of both Task2 and Gpr4, two CO2/pH sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2 chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.

Knockdown of PHOX2B in the retrotrapezoid nucleus reduces the central CO2 chemoreflex in rats.

PHOX2B is a transcription factor essential for the development of different classes of neurons in the central and peripheral nervous system. Heterozygous mutations in the PHOX2B coding region are responsible for the occurrence of Congenital Central Hypoventilation Syndrome (CCHS), a rare neurological disorder characterised by inadequate chemosensitivity and life-threatening sleep-related hypoventilation. Animal studies suggest that chemoreflex defects are caused in part by the improper development or function of PHOX2B expressing neurons in the retrotrapezoid nucleus (RTN), a central hub for CO2 chemosensitivity. Although the function of PHOX2B in rodents during development is well established, its role in the adult respiratory network remains unknown. In this study, we investigated whether reduction in PHOX2B expression in chemosensitive neuromedin-B (NMB) expressing neurons in the RTN altered respiratory function. Four weeks following local RTN injection of a lentiviral vector expressing the short hairpin RNA (shRNA) targeting Phox2b mRNA, a reduction of PHOX2B expression was observed in Nmb neurons compared to both naive rats and rats injected with the non-target shRNA. PHOX2B knockdown did not affect breathing in room air or under hypoxia, but ventilation was significantly impaired during hypercapnia. PHOX2B knockdown did not alter Nmb expression but it was associated with reduced expression of both Task2 and Gpr4, two CO2/pH sensors in the RTN. We conclude that PHOX2B in the adult brain has an important role in CO2 chemoreception and reduced PHOX2B expression in CCHS beyond the developmental period may contribute to the impaired central chemoreflex function.

Lung function in children residents in the largest coal region in Brazil.

Coal mining activities release harmful air pollutants, which affect children's health, particularly the lung function. Brazil has a large coal reserve in the southern region, where a coal-fired power plant and two coal mines are located. The study aimed to evaluate the prevalence of altered respiratory function and associated factors in children living in this region. A cross-sectional study was conducted in seven cities. It collected socioeconomic and demographic, prenatal and postnatal care, neonatal outcomes, child health information as well as lung function and air quality. The study included 396 children who lived in a high socio-environmental vulnerability due to low education levels and family income, high percentage of unemployed and families with a high bedroom density. There was a high prevalence of preterm birth, low birth weight and long-term exposure to environmental conditions. The most common respiratory problem in the parents was rhinitis, while in the children was wheezing and pneumonia. The prevalence of respiratory function alteration in the region was 7.78%. Variables associated with altered respiratory function were passive smoking, low birth weight, history of wheezing. The concentration of pollutants was equivalent when comparing stations within the coal mining host town (Candiota) and surrounding towns.

Septoplasty: Study of Prognostic Factors of Success (About 250 Cases)

Background: Septoplasty is a common surgical procedure in ENT where the objective is essentially functional and which allows the correction of septal deviations responsible for discomfort and alterations of respiratory function.

Changes in respiratory structure and function after traumatic cervical spinal cord injury: observations from spinal cord and brain.

Respiratory difficulties and mortality following severe cervical spinal cord injury (CSCI) result primarily from malfunctions of respiratory pathways and the paralyzed diaphragm. Nonetheless, individuals with CSCI can experience partial recovery of respiratory function through respiratory neuroplasticity. For decades, researchers have revealed the potential mechanism of respiratory nerve plasticity after CSCI, and have made progress in tissue healing and functional recovery. While most existing studies on respiratory plasticity after spinal cord injuries have focused on the cervical spinal cord, there is a paucity of research on respiratory-related brain structures following such injuries. Given the interconnectedness of the spinal cord and the brain, traumatic changes to the former can also impact the latter. Consequently, are there other potential therapeutic targets to consider? This review introduces the anatomy and physiology of typical respiratory centers, explores alterations in respiratory function following spinal cord injuries, and delves into the structural foundations of modified respiratory function in patients with CSCI. Additionally, we propose that magnetic resonance neuroimaging holds promise in the study of respiratory function post-CSCI. By studying respiratory plasticity in the brain and spinal cord after CSCI, we hope to guide future clinical work.

893: EXOSOMES FROM MESENCHYMAL STEM CELLS ALLEVIATE ASPIRATION-INDUCED LUNG INJURY IN MICE

Introduction: With acidic fluid, the particulate component of the aspirate and pepsin, and bacteria from the oral cavity, gastric or oropharyngeal contents aspiration readily induces lung injury. Effective therapy remains lacking to date. The exaggerated inflammatory response has been identified as one crucial mechanism that mediates the development of lung injury in this regard. Exosomes from mesenchymal stem cells (MSCs) possess a potent anti-inflammation capacity. Based on these data, we thus conjectured that exosomes from MSCs may mitigate aspiration-induced acute lung injury. To elucidate further on this issue, we thus conducted this murine study. Methods: Adult male C57BL/6 mice were randomly allocated to the Sham group (oropharyngeal aspiration of normal saline), the AP group (oropharyngeal aspiration of mimic gastric content) or the AP-EXO group (AP plus exosomes) (n=6 in each group). The mimic gastric content consisted an acidic (pH 1.6) mixture of 12mg/mL ThickenUp®, 25μL pepsin (2mg/mL) and 20μL lipopolysaccharide (2.5mg/mL). In the AP-EXO group, mice received exosomes (1x10^8 particles/mouse, intratracheal, isolated from human placenta-derived MSCs) at 2 and 24 hours after aspiration. All mice were closely monitored for 48 hours, and each group’s lung injury level was measured. Results: Aspiration induces significant alterations in respiratory function, as our data revealed significantly higher airway resistance and lower forced expiratory volume in 0.1 seconds (FEV0.1) and dynamic compliance in mice of the AP group compared with the Sham group (all p< 0.001). Aspiration also induces significant airway inflammation, lung tissue edema and lung injury, as our data revealed significantly higher cell numbers in bronchoalveolar fluid, wet/dry weight ratio of lung tissue and lung injury score in mice of the AP group compared with the Sham group (all p< 0.001). These adverse effects of aspiration were mitigated by exosomes from MSCs, as our data demonstrated significantly lower airway resistance and, in contrast, higher FEV0.1 and dynamic compliance. Also, cell number in BALF, wet/dry weight ratio of lung tissues and lung injury score decreased in mice of the AP-EXO group compared with the AP group (all p< 0.001). Conclusions: Exosomes from MSCs mitigate aspiration-induced acute lung injury in mice.

Lung and chest wall volume during vital capacity manoeuvre in Osteogenesis Imperfecta

BackgroundAlthough Osteogenesis Imperfecta (OI) affects the connective tissue, pulmonary function might be compromised because of thoracic deformities. OI is known to be a restrictive lung disease, but spirometry provides global measurement without localizing the site of the restriction. Opto-electronic plethysmography (OEP), is a non-invasive method able to underline altered respiratory function as well as ventilatory thoraco-abdominal paradoxes during spontaneous breathing. We aimed to reconstruct the thoraco-abdominal surface, to perform local analyses of trunk motion and to make quantitative comparison of trunk shape and respiratory kinematics according to OI severity, particularly during maximal inspiratory and expiratory expansions. This is a cross-sectional study where we have studied the thoraco-abdominal compartmental analysis in 26 adult OI patients (14 Type III) at rest and during vital capacity manoeuvre using OEP. We have also applied a new method that created realistic and accurate 3D models to perform local analyses of trunk motion and to make quantitative comparison of trunk shape and respiratory kinematics.ResultsType III patients were characterized by lower spirometric lung volume, by lower sleep quality, by a more compressed thoracic configuration aggravated by severe scoliosis, by reduced global expansion at rest and during maximal maneuvers because of the reduced expansion of the pulmonary ribcage at rest (12% vs. 65% in healthy subjects), during maximal inspiration (37% vs. 69%) and expiration (16% vs. 68%) with local paradoxical movement occurring on the side of the ribcage region.ConclusionThe kinematics of the trunk changed to compensate for the severe structural deformities by shifting the expansion in the abdomen both at rest and during maximal manoeuvre because of a restricted thorax. For the first time, we have quantified and localized the site of the restriction in OI patients in the lateral part of the thorax. The 3D analysis proposed seemed a promising graphical immediate new method for pathophysiology study of chest wall restriction.

Respiratory dysfunction in two rodent models of chronic epilepsy and acute seizures and its link with the brainstem serotonin system

Patients with drug-resistant epilepsy can experience respiratory alterations, notably during seizures. The mechanisms underlying long-term alterations in respiratory function remain unclear. As the brainstem 5-HT system is a prominent modulator of respiratory function, this study aimed at determining whether epilepsy is associated with alterations in both the respiratory function and brainstem serotonin (5-HT) system in rats. Epilepsy was triggered by pilocarpine-induced status epilepticus in rats. Our results showed that 30–50% of epileptic (EPI) rats exhibited a sharp decrease in oxygen consumption (SDOC), low metabolic rate of oxygen, and slow regular ventilation (EPI/SDOC + rats). These alterations were detected only in rats with chronic epilepsy, independent of behavioral seizures, were persistent over time, and not associated with death. In these rats, 5-HT fiber density in the nucleus tractus solitarius was lower than that in the control and EPI/SDOC− rats. Both EPI/SDOC + rats and DBA/2 mice that present with audiogenic-induced seizure followed by fatal respiratory arrest—a model of sudden and expected death in epilepsy—had increased transcript levels of tryptophan hydroxylase 2 and 5-HT presynaptic transporter. Thus, our data support that 5-HT alterations are associated with chronic and acute epilepsy-related respiratory dysfunction.

Diaphragmatic Activity and Respiratory Function Following C3 or C6 Unilateral Spinal Cord Contusion in Mice.

Simple SummaryTetraplegia is one of the most devastating conditions that an individual can sustain and affects more than 2.5 million people worldwide. Tetraplegia not only affects mobility but also impacts spontaneous breathing such that survivors can be rendered ventilator dependent and have increased mortality. Although no treatment can restore respiratory function after tetraplegia, there is a need for more exploratory studies defining therapeutic approaches to ameliorate respiratory decline in tetraplegia. Here, we studied two models of tetraplegia mimicking human forms of injury, using spinal cord contusion in mice, either above the third cervical metameric segment (C3 model) or below the sixth cervical metameric segment (C6 model) innervation of the phrenic nerves. These nerves are responsible for contraction of the diaphragm, the main inspiratory muscle. Using measurements of spontaneous breathing and muscle activity of the diaphragm, we found reduced diaphragmatic activity in both models, but only the C3 model led to reduced spontaneous breathing similar to what is seen in humans with tetraplegia. Moreover, we found a decline in basal contractility of the diaphragm in the C3 model only. We conclude that the C3 model is an appropriate model to explore interventions aimed at restoring breathing following tetraplegia.The majority of spinal cord injuries (SCIs) are cervical (cSCI), leading to a marked reduction in respiratory capacity. We aimed to investigate the effect of hemicontusion models of cSCI on both diaphragm activity and respiratory function to serve as preclinical models of cervical SCI. Since phrenic motoneuron pools are located at the C3–C5 spinal level, we investigated two models of preclinical cSCI mimicking human forms of injury, namely, one above (C3 hemicontusion—C3HC) and one below phrenic motoneuron pools (C6HC) in wild-type swiss OF-1 mice, and we compared their effects on respiratory function using whole-body plethysmography and on diaphragm activity using electromyography (EMG). At 7 days post-surgery, both C3HC and C6HC damaged spinal cord integrity above the lesion level, suggesting that C6HC potentially alters C5 motoneurons. Although both models led to decreased diaphragmatic EMG activity in the injured hemidiaphragm compared to the intact one (−46% and −26% in C3HC and C6HC, respectively, both p = 0.02), only C3HC led to a significant reduction in tidal volume and minute ventilation compared to sham surgery (−25% and −20% vs. baseline). Moreover, changes in EMG amplitude between respiratory bursts were observed post-C3HC, reflecting a change in phrenic motoneuronal excitability. Hence, C3HC and C6HC models induced alteration in respiratory function proportionally to injury level, and the C3HC model is a more appropriate model for interventional studies aiming to restore respiratory function in cSCI.

ASSESSMENT OF RESPIRATORY FUNCTION IN PATIENTS AFTER SARS-COV-2 LUNG DISEASE

TOPIC: Lung Pathology TYPE: Original Investigations PURPOSE: The study aims to evaluate the respiratory function of a patients' cohort with previous SARS-COV-2 pneumonia, admitted to the ASST-Spedali Civili of Brescia, after hospital discharge. METHODS: 88 patients were analyzed 4-6 months after hospital discharge. 40 had been admitted to Internal Medicine Department (IMD) for mild or moderate disease, and 48 to Intensive Care Unit (ICU) for severe disease. All patients underwent spirometry with maximal flow-volume curve and lung volumes and diffusion lung capacity (DLCO) measurements. All parameters were assessed in percent of predicted. RESULTS: In the cohort discharged from the IMD, 38% of patients showed at least one altered respiratory function parameter. In contrast, in the cohort of patients discharged from the ICU, 62% showed at least one altered parameter (p<0.01). In both the cohorts, DLCO was the most frequently altered parameter (33% of the patients discharged from the IMD, and 50% of the patients discharged from the ICU, respectively).The patients were then divided into 3 groups: patients with only Total Lung Capacity (TLC) < 80% pred.;patients with DLCO < 80% pred.;patients with both TLC and DLCO < 80% pred. 5% of patients discharged from the IMD had only restrictive deficit, 20% had only lung diffusion impairment, and 10% had both restrictive deficit and lung diffusion impairment. 8% of patients discharged from the ICU had only restrictive deficit, 27% had only lung diffusion impairment, and 23% showed both restrictive deficit and lung diffusion impairment. CONCLUSIONS: After 4-6 months from hospital discharge, approximately two/third of patients recovered completely from mild-to-moderate COVID-19 lung disease, but this was the case only in 38% of patients after severe SARS-COV-2 pneumonia. The coexistence of both restrictive deficit and lung diffusion impairment was more frequent in patients discharged from the ICU. While residual lung volume reduction alone was infrequent in both cohorts, lung diffusion impairment alone was often observed in both cohorts without significant differences. CLINICAL IMPLICATIONS: Complete respiratory function tests performed as a follow-up in patients hospitalized for moderate to severe COVID-19 lung disease are needed to provide an accurate description of their residual respiratory condition. DISCLOSURES: No relevant relationships by Manuela Ciarfaglia, source=Web Response No relevant relationships by Jordan Franz Giordani, source=Web Response No relevant relationships by Michele Guerini, source=Web Response No relevant relationships by Rossano Montori, source=Web Response No relevant relationships by Nicla Orzes, source=Web Response No relevant relationships by Laura Pini, source=Web Response No relevant relationships by Alessandro Pini, source=Web Response No relevant relationships by Claudio Tantucci, source=Web Response

A Case Report of Silicosis: Culprit of Progressive Massive Fibrosis

Silicosis is a fibronodular lung disease secondary to the inhalation of crystalline silica dust. It had continued to cause significant morbidity and mortality worldwide. Here is a case of a 63-year-old woman, a lifelong non-smoker who complained of intermittent wheezing since retired 8 years ago. She had worked in the clay and piping industry for more than a decade. She wore only a simple 3-ply face mask at work without other protective devices. She had multiple hospital admissions for acute exacerbation of chronic lung disease for the past several years. Respiratory examinations revealed bilateral fine crepitations and occasional rhonchi on auscultation. Chest radiograph revealed ground glass changes. Pulmonary function testing showed an irreversible severe obstruction picture with an FEV1 of 45%. High resolution computed tomography thorax demonstrated hyperinflated lungs with emphysematous changes and multiple nodules over subpleural region, conglomerate mass with calcifications over bilateral lungs. Her imaging findings combined with a significant occupational history were suggestive of progressive massive fibrosis (PMF) due to silicosis. She is currently being treated with several inhalers and does not require home oxygen therapy. She is suffering from accelerated silicosis which may potentially progress to radiological deterioration, altered respiratory function and premature death. Therefore, it is essential to avoid any potential hazards that may predispose to silicosis.

Scoping review on clinical definition of bovine respiratory disease complex and related clinical signs in dairy cows

Bovine respiratory disease complex (BRD) is a worldwide multifactorial infectious disease. Antimicrobials are commonly used for treating BRD because bacteria are often involved. The clinical diagnosis of BRD is a challenge, especially in adult dairy cows, where information on this syndrome is scant. Having a definition based on consistent and reliable clinical signs would improve the accuracy of BRD diagnosis and could help to develop an optimal treatment approach by an early detection. The aim of this scoping review was to review clinical signs that could be recognized by producers in dairy cattle suffering from naturally occurring infectious respiratory disease, as reported in the literature. A review of the literature was performed for articles published between January 1, 1990 and January 1, 2020. The search of literature in English, French, and Italian languages included 2 different databases (Pubmed, https://pubmed.ncbi.nlm.nih.gov/; CAB abstract, https://www.cabi.org/publishing-products/cab-abstracts/). Clinical signs were categorized as follows: (1) "general manifestations of disease," which included behavioral changes or fever; (2) "alterations in respiratory function," which included clinical signs specifically associated with the respiratory tract examination; and (3) "clinical signs of other body systems," which included clinical signs related to other systems such as diarrhea or subcutaneous emphysema. The focus of the review was on clinical signs that could be monitored by animal handlers and producers. A total of 1,067 titles were screened, and 23 studies were finally included. The most common general clinical signs were increased body temperature (reported in 83% of studies, n = 19), change in feed intake (26%, n = 6), altered mentation (22%, n = 5), and decreased milk production (17%, n = 4). The alterations in respiratory function noted were nasal discharge (74%, n = 17), cough (65%, n = 15), altered respiratory dynamic or dyspnea (61%, n = 14), increased respiratory rate (43%, n = 10), and ocular discharge or lacrimation (30%, n = 7). The clinical signs associated with infectious respiratory disease reported in the 23 studies generally lacked a clear description of what constitutes a deviation from normality (0-50% of studies clearly reported what was considered normal versus abnormal depending on the clinical signs). This limitation prevented any comparison between studies that apparently reported the same "clinical sign," but possibly referred to a different assessment and definition of what was considered normal versus abnormal. Therefore, the definition of clinical signs in a repeatable way with validated interobserver agreement to determine the optimal combination for the diagnosis of BRD in dairy cows is needed. This could lead to a more judicious use of antimicrobials for respiratory disease in adult dairy cows.

The displacement of frataxin from the mitochondrial cristae correlates with abnormal respiratory supercomplexes formation and bioenergetic defects in cells of Friedreich ataxia patients.

Friedreich ataxia (FRDA) is a neurodegenerative disease resulting from a severe decrease of frataxin (FXN). Most patients carry a GAA repeat expansion in both alleles of the FXN gene, whereas a small fraction of them are compound heterozygous for the expansion and a point mutation in the other allele. FXN is involved in the mitochondrial biogenesis of the FeS-clusters. Distinctive feature of FRDA patient cells is an impaired cellular respiration, likely due to a deficit of key redox cofactors working as electrons shuttles through the respiratory chain. However, a definite relationship between FXN levels, FeS-clusters assembly dysregulation and bioenergetics failure has not been established. In this work, we performed a comparative analysis of the mitochondrial phenotype of cell lines from FRDA patients, either homozygous for the expansion or compound heterozygotes for the G130V mutation. We found that, in healthy cells, FXN and two key proteins of the FeS-cluster assembly machinery are enriched in mitochondrial cristae, the dynamic subcompartment housing the respiratory chain. On the contrary, FXN widely redistributes to the matrix in FRDA cells with defects in respiratory supercomplexes assembly and altered respiratory function. We propose that this could be relevant for the early mitochondrial defects afflicting FRDA cells and that perturbation of mitochondrial morphodynamics could in turn be critical in terms of disease mechanisms.

Severity assessment of non-cystic fibrosis bronchiectasis by the FACED score

Objectives: Bronchiectasis (BE) is a major health problem associated with a high morbidity and mortality. This study aimed to determine the relation of the FACED score (a multidimensional score contributing to stratify patients into risk categories) with the severity of non-cystic fibrosis bronchiectasis (NCFB) among our population. Materials and Methods: This is a retrospective single center study of 105 consecutive patients with NCFB hospitalized for acute exacerbations (AE) at the Department of Respiratory Medicine of Fattouma Bourguiba Teaching Hospital in Monastir (Tunisia) between January 2005 and December 2017. Patients were divided into two groups (G): G1: FACED Score ≤ 2 and G2: FACED score ≥3. We compared different severity parameters of BE between the two groups. Results: The study included 105 patients with NCFB. Patients of G2 had more comorbidities (P = 0.028), an altered respiratory function with a lower forced vital capacity (G1:2.73, G2:1.33 L; P &lt; 0.001), a decreased PaO2 (88 vs. 68 mmHg; P &lt; 0.001), a high CO2 level (P &lt; 0.001), and a higher number of AE/year (0.96, 2.12 AE/year;P &lt; 0.001). Hospitalizations for AE of G2 were characterized by a lower PaO2, a higher PaCO2 (P &lt; 0.001), a longer course of antibiotic (P &lt; 0.001) with an extended hospitalization (P = 0.007). An ultimate evolution toward chronic respiratory failure was more common in G2 (P &lt; 0.001). Conclusion: A high FACED score is associated with more symptoms, an altered respiratory function, a higher number and more severe AE, more health-care utilization with worse outcomes. Further studies are necessary to evaluate the impact of such scales in clinical practice.

Abdominal wall incisional hernia repair improves respiratory function: results after 3\xa0years of follow-up

PurposeHernias severely impact patient quality of life (QoL), and 80% of patients require a surgical operation. Moreover, hernias are responsible for respiratory function alterations. This study aims to investigate the postoperative alterations in respiratory function after open ventral hernia repair in patients with incisional hernia.MethodsPatients operated on at the Policlinico “Paolo Giaccone” at Palermo University Hospital between January 2015 and December 2016 were identified in a prospective database. Fifty-one patients were enrolled in the study. The respiratory outcome measures used were forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC ratio, peak expiratory flow (PEF) and PEF percentage (%PEF). The timepoints at which the parameters listed were assessed were t0, 1 week before the surgical operation; t1, 12 months later; and t2, 3 years later.ResultsThe difference between mean preoperative and postoperative PEF was significant [t0 4.32 (4.03–7.92), t1 6.7 (4.27–8.24) with p = 0.012 and t2 6.5 (4.25–8.21) with p = 0.026]. The %PEF increased from 75% preoperatively to 87% at t1 (p = 0.009) and to 85% at t2 (p = 0.03). No differences were found in the comparison of pre- and postoperative FVC, FEV1 or FEV1/FVC ratio.ConclusionThe improvement in respiratory measures suggests the importance of abdominal wall restoration to recover functional activity of respiratory function.

87-OR: NF Kappa B Expression Is Related to Diabetes and Impaired Respiratory Capacity of Human Ventricular Myocardium

Nuclear factor kappa-B (NFkB) has been postulated to induce cardiac fibrosis and dysfunction in heart failure and triggers inflammatory pathways. NFkB can be induced by damaged mitochondria. Its association with myocardial mitochondrial respiratory function in non-ischemic diabetes-related heart failure in humans is yet unclear. We hypothesized that human ventricular myocardial NFkB expression (i) is increased by type 2 diabetes mellitus (T2DM), and (ii) relates to reduced myocardial mitochondrial respiration. Heart transplant recipients with or without T2DM (as determined by oral glucose tolerance test), about to undergo post-transplant surveillance endomyocardial biopsies, were included, if they had received hearts from donors without T2DM. Thus, time since transplantation equaled diabetes-exposure of the transplanted hearts (2.9±2.4 years). We assessed normalized NFkB p105 subunit (NFkB1) mRNA expression using real-time PCR and myocardial mitochondrial respiration using high-resolution respirometry. Study participants (T2DM: n=17, Non-DM: n=32) had no histological signs of allograft rejection, heart failure (left ventricular ejection fraction 66.2±6.5%) or coronary artery disease. Age and sex distribution were similar between Non-DM and T2DM (p=0.50; p=0.40, respectively). Myocardial NFkB1 expression was 60% higher in T2DM than in Non-DM (0.28 [0.21-0.44] vs. 0.45 [0.29-0.71] arbitrary units, p&amp;lt;0.05). Fasting blood glucose, but not fasting free fatty acids (p=0.55), related to myocardial NFkB1 mRNA expression (r=0.31; p&amp;lt;0.05). NFkB1 expression related inversely to state 3 respiration of fatty acids and glutamate (r=-0.33; p&amp;lt;0.05), suggesting impaired complex I-related respiration. Our findings support the concept of a key role of NFkB in diabetes-related heart failure via altered myocardial respiratory function in humans. NFkB1 might therefore serve as a future target for treating diabetes-related heart disease. Disclosure E. Zweck: None. D. Scheiber: None. T. Jelenik: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. P. Horn: None. D. Pesta: None. D. Lassner: None. H. Schultheiss: None. U. Boeken: None. P. AKhyari: None. A. Lichtenberg: None. M. Kelm: None. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S. R. Westenfeld: None. J. Szendroedi: None. Funding German Research Council (SFB1116); Heinrich-Heine University

Causes of, and countermeasures to, increased ventilatory drive in tetraplegia.

Causes of, and countermeasures to, increased ventilatory drive in tetraplegia.

Mapping mitochondrial respiratory chain deficiencies by respirometry: Beyond the Mito Stress Test

Cell-based respirometers, such as the Seahorse Extracellular Flux Analyzer, are valuable tools to assess the functionality of mitochondria within adherent neurons, as well as other cell types. The Mito Stress Test is the most frequently employed protocol of drug additions to evaluate mitochondrial bioenergetic function. Sequential exposure of cells to an ATP synthase inhibitor such as oligomycin and an uncoupler such as FCCP cause changes in oxygen consumption rate that allow estimation of the cellular efficiency and capacity for mitochondrial ATP synthesis. While a useful first step in assessing whether an experimental treatment or genetic manipulation affects mitochondrial energetics, the Mito Stress Test does not identify specific sites of altered respiratory chain function. This article discusses limitations of the Mito Stress Test, proposes a refined protocol for comparing cell populations that requires independent drug titrations at multiple cell densities, and describes a stepwise series of respirometry-based assays that “map” locations of electron transport deficiency. These include strategies to test for cytochrome c release, to probe the functionality of specific electron transport chain complexes within intact or permeabilized cells, and to measure NADH oxidation by the linked activity of Complexes I, III, and IV. To illustrate utility, we show that although UK5099 and ABT-737 each decrease the spare respiratory capacity of cortical neurons, the stepwise assays reveal different underlying mechanisms consistent with their established drug targets: deficient Complex I substrate supply induced by the mitochondrial pyruvate carrier inhibitor UK5099 and cytochrome c release induced by the anti-apoptotic BCL-2 family protein inhibitor ABT-737.

Reabilitação da Função Respiratória na pessoa com pneumonia bacteriana secundária ao Influenza A: estudo de caso

Introdução: Os meses de Outono e Inverno estão associados a um aumento da epidemia sazonal da gripe responsável por 3 a 5 milhões de casos de doença grave. A sobre-infeção bacteriana secundária assume-se como a complicação mais frequente, com elevados índices de internamento. Aos enfermeiros especialistas em enfermagem de reabilitação são reconhecidas capacidades mediante um conjunto de intervenções terapêuticas para proporcionar a recuperação da pessoa portadora de patologia respiratória. Objetivo: Identificar os ganhos em saúde sensíveis aos cuidados de enfermagem de reabilitação na otimização da função respiratória numa pessoa com o diagnóstico de pneumonia adquirida na comunidade por streptococcus pneumoniae secundária à infeção por Influenza A. Método: Estudo de abordagem qualitativa, tipo estudo de caso. Consiste na utilização do processo de enfermagem, com recurso ao Padrão Documental dos Cuidados da Especialidade de Enfermagem de Reabilitação. É apresentado o caso de uma pessoa idosa com alteração da função respiratória, necessitando de oxigenoterapia e capacidade de expetorar comprometida. Foram cumpridos os princípios éticos em investigação. Resultados: Com a implementação do plano de intervenção constituído por quadro dias, foram verificados ganhos na redução da sensação de dispneia; redução do aporte de oxigenoterapia; redução da quantidade de secreções; melhoria na auscultação pulmonar do murmúrio vesicular. Conclusões: Verifica-se que com a implementação de um plano de cuidados de enfermagem de reabilitação individualizado pode-se contribuir significativamente na promoção da recuperação da pessoa com patologia respiratória restritiva. Descritores: Exercícios Respiratórios; Pneumonia Bacteriana; Enfermeiro Especialista em Enfermagem de Reabilitação; Relatos de Casos.

Paralisia hemidiafragmática após bloqueio supraclavicular guiado por ultrassom: um estudo coorte prospectivo

Background and objectivesThe frequent onset of hemidiaphragmatic paralysis during interscalene block restricts its use in patients with respiratory insufficiency. Supraclavicular block could be a safe and effective alternative. Our primary objective was to assess the incidence of hemidiaphragmatic paralysis following ultrasound‐guided supraclavicular block and compare it to that of interscalene block. MethodsAdults warranting elective shoulder surgery under regional anesthesia (Toulouse University Hospital) were prospectively enrolled from May 2016 to May 2017 in this observational study. Twenty millilitres of 0.375% Ropivacaine were injected preferentially targeted to the “corner pocket”. Diaphragmatic excursion was measured by ultrasonography before and 30 minutes after regional anesthesia. A reduction ≥ 25% in diaphragmatic excursion during a sniff test defined the hemidiaphragmatic paralysis. Dyspnoea and hypoxaemia were recorded in the recovery room. Predictive factors of hemidiaphragmatic paralysis (gender, age, weight, smoking, functional capacity) were explored. Postoperative pain was also analysed. ResultsForty‐two and 43 patients from respectively the supraclavicular block and interscalene block groups were analysed. The incidence of hemidiaphragmatic paralysis was 59.5% in the supraclavicular block group compared to 95.3% in the interscalene block group (p < 0.0001). Paradoxical movement of the diaphragm was more common in the interscalene block group (RR = 2, 95% CI 1.4-3; p = 0.0001). A similar variation in oxygen saturation was recorded between patients with and without hemidiaphragmatic paralysis (p = 0.08). No predictive factor of hemidiaphragmatic paralysis could be identified. Morphine consumption and the highest numerical rating scale (NRS) at 24 hours did not differ between groups. ConclusionsGiven the frequent incidence of hemidiaphragmatic paralysis following supraclavicular block, this technique cannot be recommended for patients with an altered respiratory function.