Airway narrowing and bronchodilation to deep inspiration in bronchial segments from subjects with and without reported asthma

2013 ◽  
Vol 114 (10) ◽  
pp. 1460-1471 ◽  
Author(s):  
Peter B. Noble ◽  
Robyn L. Jones ◽  
Alvenia Cairncross ◽  
John G. Elliot ◽  
Howard W. Mitchell ◽  
...  
Keyword(s):  
Mechanical Stretch ◽  
Control Group ◽  
Deep Inspiration ◽  
Airway Wall ◽  
Normal Response ◽  
Airway Narrowing ◽  
History Of ◽  
Static Conditions

The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma ( n = 5) or had no history of asthma ( n = 8). In vitro airway narrowing in response to acetylcholine was assessed to determine maximal bronchoconstriction and sensitivity, under static conditions and during simulated tidal and DI maneuvers. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the airway smooth muscle (ASM) layer. Airways from subjects with a history of asthma had increased ASM ( P = 0.014), greater maximal airway narrowing under static conditions ( P = 0.003), but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer ( r = 0.58, P = 0.039). In tidally oscillating airways, DI produced bronchodilation in airways from the control group ( P = 0.0001) and the group with a history of asthma ( P = 0.001). While bronchodilation to DI was reduced with increased airway narrowing ( P = 0.02; r = −0.64)), when the level of airway narrowing was matched, there was no difference in magnitude of bronchodilation to DI between groups. Results suggest that greater ASM mass in asthma contributes to exaggerated airway narrowing in vivo. In comparison, the airway wall in asthma may have a normal response to mechanical stretch during DI. We propose that increased maximal airway narrowing and the reduced bronchodilatory response to DI in asthma are independent.

Responsiveness of the human airway in vitro during deep inspiration and tidal oscillation

2011 ◽  
Vol 110 (6) ◽  
pp. 1510-1518 ◽  
Author(s):  
Peter B. Noble ◽  
Robyn L. Jones ◽  
Elangovan Thaya Needi ◽  
Alvenia Cairncross ◽  
Howard W. Mitchell ◽  
...  
Keyword(s):  
Airflow Obstruction ◽  
Mechanical Stretch ◽  
Airway Responsiveness ◽  
Organ Bath ◽  
Deep Inspiration ◽  
Airway Narrowing ◽  
Tidal Oscillation ◽  
Human Airways ◽  
Static Conditions

In healthy individuals, deep inspiration produces bronchodilation and reduced airway responsiveness, which may be a response of the airway wall to mechanical stretch. The aim of this study was to examine the in vitro response of isolated human airways to the dynamic mechanical stretch associated with normal breathing. Human bronchial segments ( n = 6) were acquired from patients without airflow obstruction undergoing lung resection for pulmonary neoplasms. The side branches were ligated and the airways were mounted in an organ bath chamber. Airway narrowing to cumulative concentrations of acetylcholine (3 × 10−6 M to 3 × 10−3 M) was measured under static conditions and in the presence of “tidal” oscillations with intermittent “deep inspiration.” Respiratory maneuvers were simulated by varying transmural pressure using a motor-controlled syringe pump (tidal 5 to 10 cmH2O at 0.25 Hz, deep inspiration 5 to 30 cmH2O). Airway narrowing was determined from decreases in lumen volume. Tidal oscillation had no effect on airway responses to acetylcholine which was similar to those under static conditions. Deep inspiration in tidally oscillating, acetylcholine-contracted airways produced potent, transient (<1 min) bronchodilation, ranging from full reversal in airway narrowing at low acetylcholine concentrations to ∼50% reversal at the highest concentration. This resulted in a temporary reduction in maximal airway response ( P < 0.001), without a change in sensitivity to acetylcholine. Our findings are that the mechanical stretch of human airways produced by physiological transmural pressures generated during deep inspiration produces bronchodilation and a transient reduction in airway responsiveness, which can explain the beneficial effects of deep inspiration in bronchial provocation testing in vivo.

scholarly journals Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

2002 ◽  
Vol 93 (4) ◽  
pp. 1296-1300 ◽  
Author(s):  
Debra J. Turner ◽  
Peter B. Noble ◽  
Matthew P. Lucas ◽  
Howard W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Porcine Model ◽  
Smooth Muscle Contraction ◽  
Airway Wall ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Airway Narrowing

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

Mechanical ventilation promotes lung tumor spread by modulation of cholesterol cell content

2021 ◽  
pp. 2101470
Author(s):  
Inés López-Alonso ◽  
Cecilia López-Martínez ◽  
Paula Martín-Vicente ◽  
Laura Amado-Rodríguez ◽  
Adrián González-López ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Cancer Cells ◽  
Lung Tumor ◽  
Mechanical Stretch ◽  
Lung Tumors ◽  
Cyclic Stretch ◽  
Tumor Spread ◽  
Static Conditions

Mechanical stretch of cancer cells can alter their invasiveness. During mechanical ventilation, lungs may be exposed to an increased amount of stretch, but the consequences on lung tumors have not been explored. To characterize the influence of mechanical ventilation on the behavior of lung tumors, invasiveness assays and transcriptomic analyses were performed in cancer cell lines cultured in static conditions or under cyclic stretch. Mice harbouring lung melanoma implants were submitted to mechanical ventilation and metastatic spread was assessed. Additional in vivo experiments were performed to determine the mechano-dependent specificity of the response. Incidence of metastases was studied in a cohort of lung cancer patients that received mechanical ventilation compared with a matched group of non-ventilated patients. Stretch increases invasiveness in melanoma B16F10luc2 and lung adenocarcinoma A549 cells. We identified a mechanosensitive upregulation of pathways involved in cholesterol processing in vitro, leading to an increase in PCSK9 and LDLR expression, a decrease in intracellular cholesterol and preservation of cell stiffness. A course of mechanical ventilation in mice harboring melanoma implants increased brain and kidney metastases two weeks later. Blockade of PCSK9 using a monoclonal antibody increased cell cholesterol and stiffness and decreased cell invasiveness in vitro and metastasis in vivo. In patients, mechanical ventilation increased PCSK9 abundance in lung tumors and the incidence of metastasis, thus decreasing survival. Our results suggest that mechanical stretch promote invasiveness of cancer cells, which may have clinically relevant consequences. Pharmacological manipulation of cholesterol endocytosis could be a novel therapeutic target in this setting.

Airway narrowing and response to simulated deep inspiration in bronchial segments from subjects with fixed airflow obstruction

2020 ◽  
Vol 128 (4) ◽  
pp. 757-767
Author(s):  
Alvenia Cairncross ◽  
Robyn L. Jones ◽  
John G. Elliot ◽  
Peter K. McFawn ◽  
Alan L. James ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Volume Fraction ◽  
Airflow Obstruction ◽  
Deep Inspiration ◽  
Airway Wall ◽  
Airway Narrowing ◽  
Fixed Airflow Obstruction

The volume fraction of extracellular matrix (ECM) within the layer of airway smooth muscle (ASM) is increased in subjects with fixed airflow obstruction. We postulated that changes in ECM within the ASM layer will impact force transmission during induced contraction and/or in response to externally applied stresses like a deep inspiration (DI). Subjects were patients undergoing lung resection surgery who were categorized as unobstructed ( n = 12) or “fixed” obstructed ( n = 6) on the basis of preoperative spirometry. The response to a DI, assessed by the ratio of isovolumic flows from maximal and partial inspirations (M/P), was also measured preoperatively. M/P was reduced in the obstructed group ( P = 0.02). Postoperatively, bronchial segments were obtained from resected tissue, and luminal narrowing to acetylcholine and bronchodilation to simulated DI were assessed in vitro. Airway wall dimensions and the volume fraction of ECM within the ASM were quantified. Maximal airway narrowing to acetylcholine ( P = 0.01) and the volume fraction of ECM within the ASM layer ( P = 0.02) were increased in the obstructed group, without a change in ASM thickness. Whereas bronchodilation to simulated DI in vitro was not different between obstructed and unobstructed groups, it was correlated with increased M/P (bronchodilation/less bronchoconstriction) in vivo ( P = 0.03). The volume fraction of ECM was inversely related to forced expiratory volume in 1 s FEV1 %predicted ( P = 0.04) and M/P ( P = 0.01). Results show that in subjects with fixed airflow obstruction the mechanical behavior of the airway wall is altered and there is a contemporaneous shift in the structural composition of the ASM layer. NEW & NOTEWORTHY Cartilaginous airways from subjects with fixed airflow obstruction have an increase in the volume fraction of extracellular matrix within the airway smooth muscle layer. These airways are also intrinsically more reactive to a contractile stimulus, which is expected to contribute to airway hyperresponsiveness in this population, often attributed to geometric mechanisms. In view of these results, we speculate on how changes in extracellular matrix may impact airway mechanics.

Biaxial distension of precision-cut lung slices

2010 ◽  
Vol 108 (3) ◽  
pp. 713-721 ◽  
Author(s):  
C. Dassow ◽  
L. Wiechert ◽  
C. Martin ◽  
S. Schumann ◽  
G. Müller-Newen ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Cell Injury ◽  
Mechanical Stretch ◽  
Longitudinal Direction ◽  
Lung Parenchyma ◽  
Cell Types ◽  
Static Conditions ◽  
Precision Cut Lung Slices

The mechanical forces acting on lung parenchyma during (mechanical) ventilation and its (patho)physiological consequences are currently under intense scrutiny. Several in vivo and cell culture models have been developed to study the pulmonary responses to mechanical stretch. While providing extremely useful information, these models do also suffer from limitations in being either too complex for detailed mechanical or mechanistic studies, or in being devoid of the full complexity present in vivo (e.g., different cell types and interstitial matrix). Therefore in the present study it was our aim to develop a new model, based on the biaxial stretching of precision-cut lung slices (PCLS). Single PCLS were mounted on a thin and flexible carrier membrane of polydimethylsiloxane (PDMS) in a bioreactor, and the membrane was stretched by applying varying pressures under static conditions. Distension of the membrane-PCLS construct was modeled via finite element simulation. According to this analysis, lung tissue was stretched by up to 38% in the latitudinal and by up to 44% in the longitudinal direction, resulting in alveolar distension similar to what has been described in intact lungs. Stretch for 5 min led to increased cellular calcium levels. Lung slices were stretched dynamically with a frequency of 15/min for 4 h without causing cell injury {3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test; live/dead straining}. These findings suggest that stretching of PCLS on PDMS-membranes may represent a useful model to investigate lung stretch in intact lung tissue in vitro for several hours.

In-vitro- und In-vivo-Wirkung von Schilddrüsenhormon auf das Wachstum von Neuroblastomzellen

1990 ◽  
Vol 29 (03) ◽  
pp. 120-124
Author(s):  
R. P. Baum ◽  
E. Rohrbach ◽  
G. Hör ◽  
B. Kornhuber ◽  
E. Busse
Keyword(s):  
Cell Differentiation ◽  
Neuroblastoma Cells ◽  
Control Group ◽  
Initial Value ◽  
Initial Rise ◽  
Biphasic Effect ◽  
Contrast Microscopy ◽  
Morphological Sign

The effect of triiodothyronine (T3) on the differentiation of cultured neuroblastoma (NB) cells was studied after 9 days of treatment with a dose of 10-4 M/106 cells per day. Using phase contrast microscopy, 30-50% of NB cells showed formation of neurites as a morphological sign of cellular differentiation. The initial rise of the mitosis rate was followed by a plateau. Changes in cyclic nucleotide content, in the triphosphates and in the activity of the enzyme ornithine decarboxylase (ODC) were assessed in 2 human and 2 murine cell lines to serve as biochemical parameters of the cell differentiation induced by T3. Whereas the cAMP level increased significantly (3 to 7 fold compared with its initial value), the cGMP value dropped to 30 to 50% of that of the control group. ATP and GTP increased about 200%, the ODC showed a decrease of about 50%. The present studies show a biphasic effect of T3 on neuroblastoma cells: the initial rise of mitotic activity is followed by increased cell differentiation starting from day 4 of the treatment.

Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Protective Effect ◽  
Cell Damage ◽  
Memory Loss ◽  
Control Group ◽  
Total Extract ◽  
Swiss Mice ◽  
Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

Analysis of the Dynamics of the Electric Capacitance of a Cell Monolayer at the Late Stages of Caco-2 cell Differentiation

2019 ◽  
Vol 35 (6) ◽  
pp. 87-90
Author(s):  
S.V. Nikulin ◽  
V.A. Petrov ◽  
D.A. Sakharov
Keyword(s):  
Impedance Spectroscopy ◽  
Cell Monolayer ◽  
Microfluidic Chips ◽  
Russian Science ◽  
Electric Capacitance ◽  
A Cell ◽  
Static Conditions ◽  
Late Stages

The real-time monitoring of electric capacitance (impedance spectroscopy) allowed obtaining evidence that structures which look like intestinal villi can be formed during the cultivation under static conditions as well as during the cultivation in microfluidic chips. It was shown in this work via transcriptome analysis that the Hh signaling pathway is involved in the formation of villus-like structures in vitro, which was previously shown for their formation in vivo. impedance spectroscopy, intestine, villi, electric capacitance, Hh The study was funded by the Russian Science Foundation (Project 16-19-10597).

Cold Plasma Treatment Promotes Full-thickness Healing of Skin Wounds in Murine Models

2021 ◽  
pp. 153473462110021
Author(s):  
Joon M. Jung ◽  
Hae K. Yoon ◽  
Chang J. Jung ◽  
Soo Y. Jo ◽  
Sang G. Hwang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Plasma Treatment ◽  
Cold Plasma ◽  
Smooth Muscle Actin ◽  
Treated Group ◽  
Control Group ◽  
Alpha Smooth Muscle Actin ◽  
Skin Wound Healing

Cold plasma can be beneficial for promoting skin wound healing and has a high potential of being effectively used in treating various wounds. Our aim was to verify the effect of cold plasma in accelerating wound healing and investigate its underlying mechanism in vitro and in vivo. For the in vivo experiments, 2 full-thickness dermal wounds were created in each mouse (n = 30). While one wound was exposed to 2 daily plasma treatments for 3 min, the other wound served as a control. The wounds were evaluated by imaging and histological analyses at 4, 7, and 11 days post the wound infliction process. Immunohistochemical studies were also performed at the same time points. In vitro proliferation and scratch assay using HaCaT keratinocytes and fibroblasts were performed. The expression levels of wound healing–related genes were analyzed by real-time polymerase chain reaction and western blot analysis. On day 7, the wound healing rates were 53.94% and 63.58% for the control group and the plasma-treated group, respectively. On day 11, these rates were 76.05% and 93.44% for the control and plasma-treated groups, respectively, and the difference between them was significant ( P = .039). Histological analysis demonstrated that plasma treatment promotes the formation of epidermal keratin and granular layers. Immunohistochemical studies also revealed that collagen 1, collagen 3, and alpha-smooth muscle actin appeared more abundantly in the plasma-treated group than in the control group. In vitro, the proliferation of keratinocytes was promoted by plasma exposure. Scratch assay showed that fibroblast exposure to plasma increased their migration. The expression levels of collagen 1, collagen 3, and alpha-smooth muscle actin were elevated upon plasma treatment. In conclusion, cold plasma can accelerate skin wound healing and is well tolerated.

Agitation Techniques to Enhance Drainage of Retained Hemothorax

2020 ◽  
pp. 155335062097800
Author(s):  
Ian A. Makey ◽  
Nitin A. Das ◽  
Samuel Jacob ◽  
Magdy M. El-Sayed Ahmed ◽  
Colleen M. Makey ◽  
...  
Keyword(s):  
Trauma Surgery ◽  
Control Group ◽  
In Vivo Experiments ◽  
Vibration Technique ◽  
Retained Hemothorax ◽  
And Control ◽  
Negative Conclusion ◽  
Benchtop Model

Background. Retained hemothorax (RH) is a common problem in cardiothoracic and trauma surgery. We aimed to determine the optimum agitation technique to enhance thrombus dissolution and drainage and to apply the technique to a porcine-retained hemothorax. Methods. Three agitation techniques were tested: flush irrigation, ultrasound, and vibration. We used the techniques in a benchtop model with tissue plasminogen activator (tPA) and pig hemothorax with tPA. We used the most promising technique vibration in a pig hemothorax without tPA. Statistics. We used 2-sample t tests for each comparison and Cohen d tests to calculate effect size (ES). Results. In the benchtop model, mean drainages in the agitation group and control group and the ES were flush irrigation, 42%, 28%, and 2.91 ( P = .10); ultrasound, 35%, 27%, and .76 ( P = .30); and vibration, 28%, 19%, and 1.14 ( P = .04). In the pig hemothorax with tPA, mean drainages and the ES of each agitation technique compared with control (58%) were flush irrigation, 80% and 1.14 ( P = .37); ultrasound, 80% and 2.11 ( P = .17); and vibration, 95% and 3.98 ( P = .06). In the pig hemothorax model without tPA, mean drainages of the vibration technique and control group were 50% and 43% (ES = .29; P = .65). Discussion. In vitro studies suggested flush irrigation had the greatest effect, whereas only vibration was significantly different vs the respective controls. In vivo with tPA, vibration showed promising but not statistically significant results. Results of in vivo experiments without tPA were negative. Conclusion. Agitation techniques, in combination with tPA, may enhance drainage of hemothorax.

Sign in / Sign up

Export Citation Format

Share Document