scholarly journals Bronchodilatory effect of deep inspiration in freshly isolated sheep lungs

2017 ◽  
Vol 312 (2) ◽  
pp. L178-L185 ◽  
Author(s):  
William D. Wong ◽  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Volume ◽  
Healthy Subjects ◽  
Airway Resistance ◽  
Deep Inspiration ◽  
Bronchial Circulation ◽  
Stretch Receptors ◽  
The Difference ◽  
Isolated Lungs

Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect. Neural reflex initiated by stretch receptors in the lung are known to inhibit the broncho-motor tone and enhance vasodilatation; the former directly reduces airway resistance, and the latter facilitates removal of contractile agonists through the bronchial circulation. If the DI effect is solely mediated by factors extrinsic to the lung, the DI effect would be absent in isolated, nonperfused lungs. Here we examined the DI effect in freshly isolated, nonperfused sheep lungs. We found that imposition of DI on isolated lungs resulted in significant bronchodilation, that this DI effect was present only after the lungs were challenged with a contractile agonist (acetylcholine or histamine), and that the effect was independent of the difference in lung volume observed pre- and post-DI. We conclude that a significant portion of the bronchodilatory DI effect stems from factors internal to the lung related to the activation of ASM.

Modulation of pulmonary stretch receptors and airway resistance by parasympathetic efferents

1984 ◽  
Vol 57 (6) ◽  
pp. 1842-1849 ◽  
Author(s):  
C. A. Richardson ◽  
D. A. Herbert ◽  
R. A. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Phrenic Nerve ◽  
Airway Resistance ◽  
Pulmonary Resistance ◽  
Nerve Activity ◽  
Firing Rates ◽  
Stretch Receptors ◽  
Pulmonary Stretch Receptors ◽  
Inspiratory Activity

Recording from pulmonary stretch receptors in the intact cervical vagus nerve revealed a novel interaction between stretch receptors and smooth muscle in the lungs of anesthetized paralyzed cats. Firing rates of pulmonary stretch receptors were modulated in step with the inflation-deflation cycle of the mechanical respirator, as expected. Firing rates of most slowly adapting receptors, but not rapidly adapting receptors, were also strongly modulated in step with the phrenic nerve activity even when the respirator was turned off and the cat motionless. The modulation of some receptors' firing rates by the inspiratory motor output was as great as the change in firing-rate in response to a lung inflation of 20 ml of air (one tidal volume). Atropine blocked the inspiratory-related modulation of slowly adapting/receptor firing rates; it did not block the inflation-related modulation. Pulmonary resistance was modulated in step with the inspiratory activity on the phrenic nerve. Hyperventilation to neural apnea (no phrenic nerve activity) reduced pulmonary resistance to its lowest level, a level equal to that produced by an injection of isoproterenol or atropine. Hypoxia during hypocapnic apnea caused bursts of inspiratory activity on the phrenic nerve accompanied by one-to-one increases in airway resistance. We conclude that the intrathoracic airway smooth muscle contracts with each neural inspiration, that the modulation of the pulmonary stretch receptors is due to a mechanical interaction with the intrathoracic airway smooth muscle, and that through the mechanical link with airway smooth muscle, stretch receptor sensitivity depends on inspiratory output, a closed loop.

Effects of lung volume on airway resistance during induced constriction in papain-treated rabbits

1996 ◽  
Vol 80 (6) ◽  
pp. 1872-1879 ◽  
Author(s):  
T. Nagase ◽  
H. Matsui ◽  
E. Sudo ◽  
T. Matsuse ◽  
M. S. Ludwig ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Lung Volume ◽  
Airway Resistance ◽  
Transpulmonary Pressure ◽  
Airway Narrowing ◽  
Tissue Resistance ◽  
Before And After ◽  
Baseline Conditions ◽  
Different Levels

It has been reported that both the elasticity of the cartilage and airway-parenchymal interdependence can modify shortening of the airway smooth muscle and airway narrowing during induced constriction. We hypothesized that induced softening of the cartilage could alter airway compliance and/or the forces of mechanical interdependence, resulting in an increased degree of airway narrowing in response to a contractile stimulus. To test this hypothesis, we compared the effects of changing lung volume on airway resistance (Raw) under baseline conditions and during methacholine (MCh)-induced constriction in papain-treated (n = 6) and control rabbits (n = 6). With use of the alveolar capsule technique, Raw was directly measured under baseline conditions at different levels of end-expiratory transpulmonary pressure (Ptp = 4-12 cmH2O). Then aerosolized MCh was delivered (0.2-25 mg/ml) and measurements were performed at different levels of Ptp (4 and 12 cmH2O). From measured tracheal flow and tracheal and alveolar pressure in open-chest animals during mechanical ventilation (tidal volume = 6 ml/kg, breathing frequency = 1 Hz), we calculated Raw by subtracting tissue resistance from lung resistance. Papain treatment significantly increased Raw both under baseline conditions and after induced constriction. We found that increasing Ptp decreased Raw before and after MCh in both groups; however, the effects of changing Ptp on Raw were less in papain-treated animals. These observations suggest that both cartilage elasticity and mechanical interdependence are important determinants of airway smooth muscle shortening. The observation that volume dependence of Raw was less in papain-treated animals is consistent with the hypothesis that papain effects significant changes in the parenchymal attachments.

Development and maintenance of force and stiffness in airway smooth muscle

2015 ◽  
Vol 93 (3) ◽  
pp. 163-169 ◽  
Author(s):  
Bo Lan ◽  
Brandon A. Norris ◽  
Jeffrey C.-Y. Liu ◽  
Peter D. Paré ◽  
Chun Y. Seow ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Solid State ◽  
Airway Smooth Muscle ◽  
Deep Inspiration ◽  
Contractile Apparatus ◽  
Tidal Breathing ◽  
Actomyosin Interaction ◽  
Filament Network

Airway smooth muscle (ASM) plays a central role in the excessive narrowing of the airway that characterizes the primary functional impairment in asthma. This phenomenon is known as airway hyper-responsiveness (AHR). Emerging evidence suggests that the development and maintenance of ASM force involves dynamic reorganization of the subcellular filament network in both the cytoskeleton and the contractile apparatus. In this review, evidence is presented to support the view that regulation of ASM contraction extends beyond the classical actomyosin interaction and involves processes within the cytoskeleton and at the interfaces between the cytoskeleton, the contractile apparatus, and the extracellular matrix. These processes are initiated when the muscle is activated, and collectively they cause the cytoskeleton and the contractile apparatus to undergo structural transformation, resulting in a more connected and solid state that allows force generated by the contractile apparatus to be transmitted to the extracellular domain. Solidification of the cytoskeleton also serves to stiffen the muscle and hence the airway. Oscillatory strain from tidal breathing and deep inspiration is believed to be the counter balance that prevents hypercontraction and stiffening of ASM in vivo. Dysregulation of this balance could lead to AHR seen in asthma.

scholarly journals The Strain on Airway Smooth Muscle During a Deep Inspiration to Total Lung Capacity

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Ynuk Bossé
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Total Lung Capacity ◽  
In Vitro Studies ◽  
Deep Inspiration ◽  
Bronchodilator Effect ◽  
Lung Capacity ◽  
Residual Capacity

The deep inspiration (DI) maneuver entices a great deal of interest because of its ability to temporarily ease the flow of air into the lungs. This salutary effect of a DI is proposed to be mediated, at least partially, by momentarily increasing the operating length of airway smooth muscle (ASM). Concerningly, this premise is largely derived from a growing body of in vitro studies investigating the effect of stretching ASM by different magnitudes on its contractility. The relevance of these in vitro findings remains uncertain, as the real range of strains ASM undergoes in vivo during a DI is somewhat elusive. In order to understand the regulation of ASM contractility by a DI and to infer on its putative contribution to the bronchodilator effect of a DI, it is imperative that in vitro studies incorporate levels of strains that are physiologically relevant. This review summarizes the methods that may be used in vivo in humans to estimate the strain experienced by ASM during a DI from functional residual capacity (FRC) to total lung capacity (TLC). The strengths and limitations of each method, as well as the potential confounders, are also discussed. A rough estimated range of ASM strains is provided for the purpose of guiding future in vitro studies that aim at quantifying the regulatory effect of DI on ASM contractility. However, it is emphasized that, owing to the many limitations and confounders, more studies will be needed to reach conclusive statements.

Combined Effect of Isoproterenol and Mechanical Oscillation on the Contractile Response of Mice Airway Smooth Muscle From Healthy and Asthmatic Subjects

2012 ◽  
Author(s):  
M. J. Jo-Avila ◽  
A. M. Al-Jumaily ◽  
J. Lu ◽  
L. Sobrevia
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Healthy Subjects ◽  
Contractile Response ◽  
Relaxation Response ◽  
Driving Mechanism ◽  
Airway Lumen ◽  
Mechanical Oscillations ◽  
Normal Breathing ◽  
Asthma Attack

The main driving mechanism during an asthma attack is the hyperconstriction of airway smooth muscle (ASM), which reduces the airway lumen and makes normal breathing difficult. The contraction can be relieved by using bronchodilator drugs such as Isoproterenol (ISO). This paper hypothesizes that mechanical oscillations may improve drug therapy when combined with ISO or used alone in asthmatic subjects. Preliminary results indicate that combining ISO with breathing equivalent mechanical oscillations tends to increase the relaxation response, as compared to ISO alone in airways from healthy subjects, but not in the same manner in asthmatic airways. The effect of superposed oscillations of 1% and 1.5% amplitude in the range 5–20 Hz applied over breathing equivalent mechanical oscillations was also assessed in the study.

Bronchodilatory effect of deep inspiration on the dynamics of bronchoconstriction in mice

2007 ◽  
Vol 103 (5) ◽  
pp. 1696-1705 ◽  
Author(s):  
Jason H. T. Bates ◽  
Ana Cojocaru ◽  
Lennart K. A. Lundblad
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Resistance ◽  
Eccentric Contraction ◽  
Positive End Expiratory Pressure ◽  
Substantial Fraction ◽  
Lung Inflation ◽  
Rate Of Increase ◽  
Model Predictions ◽  
Made In

We recently developed a computational model of an airway embedded in elastic parenchyma (Bates JH, Lauzon AM. J Appl Physiol 102: 1912–1920, 2007) that accurately mimics the time dependence of airway resistance on tidal volume and positive end-expiratory pressure (PEEP) following methacholine injection in normal animals. In the present study, we compared the model predictions of bronchodilation induced by a deep inflation (DI) of the lung following administration of the bronchial agonist methacholine to corresponding experimental measurements made in mice. We found that a DI in mice caused an immediate reduction in airway resistance when it was administered soon after intravenous injection of methacholine, while the airway smooth muscle was in the process of contracting. However, the magnitude of the reduction in resistance was greater and its subsequent rate of increase less than that predicted by the model. We found that this effect was most pronounced when the DI was given within ∼3 s following methacholine injection, again in contrast to the predictions of the model. The reduction of airway resistance was virtually independent of the rate of lung inflation during the DI, however, which agrees with model predictions. We conclude that while the model accounts for a substantial fraction of the post-DI reduction in airway resistance seen experimentally, there remain important differences between prediction and experiment that suggest that the effects of a DI are not simply due to eccentric contraction of the airway smooth muscle.

Mechanisms of Bronchoprotection by Anesthetic Induction Agents 

1999 ◽  
Vol 90 (3) ◽  
pp. 822-828 ◽  
Author(s):  
Robert H. Brown ◽  
Elizabeth M. Wagner
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Nerve Stimulation ◽  
Airway Resistance ◽  
Bronchial Artery ◽  
Random Order ◽  
Systemic Blood Pressure ◽  
Vagal Nerve ◽  
Vagal Nerve Stimulation ◽  
High Concentrations

Background Propofol and ketamine have been purported to decrease bronchoconstriction during induction of anesthesia and intubation. Whether they act on airway smooth muscle or through neural reflexes has not been determined. We compared propofol and ketamine to attenuate the direct activation of airway smooth muscle by methacholine and limit neurally mediated bronchoconstriction (vagal nerve stimulation). Methods After approval from the institutional review board, eight sheep were anesthetized with pentobarbital, paralyzed, and ventilated. After left thoracotomy, the bronchial artery was cannulated and perfused. In random order, 5 mg/ml concentrations of propofol, ketamine, and thiopental were infused into the bronchial artery at rates of 0.06, 0.20, and 0.60 ml/min. After 10 min, airway resistance was measured before and after vagal nerve stimulation and methacholine given via the bronchial artery. Data were expressed as a percent of baseline response before infusion of drug and analyzed by analysis of variance with significance set at P< or =0.05. Results Systemic blood pressure was not affected by any of the drugs (P>0.46). Baseline airway resistance was not different among the three agents (P = 0.56) or by dose (P = 0.96). Infusion of propofol and ketamine into the bronchial artery caused a dose-dependent attenuation of the vagal nerve stimulation-induced bronchoconstriction to 26+/-11% and 8+/-2% of maximum, respectively (P<0.0001). In addition, propofol caused a significant decrease in the methacholine-induced bronchoconstriction to 43+/-27% of maximum at the highest concentration (P = 0.05) Conclusions The local bronchoprotective effects of ketamine and propofol on airways is through neurally mediated mechanisms. Although the direct effects on airway smooth muscle occur at high concentrations, these are unlikely to be of primary clinical relevance.

Computational assessment of airway wall stiffness in vivo in allergically inflamed mouse models of asthma

2008 ◽  
Vol 104 (6) ◽  
pp. 1601-1610 ◽  
Author(s):  
Ana Cojocaru ◽  
Charles G. Irvin ◽  
Hans C. Haverkamp ◽  
Jason H. T. Bates
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Time Course ◽  
Airway Resistance ◽  
Allergic Inflammation ◽  
Model Fit ◽  
Airway Wall ◽  
Pulmonary Endothelium ◽  
Wall Stiffness

Allergic inflammation is known to cause airway hyperresponsiveness in mice. However, it is not known whether inflammation affects the stiffness of the airway wall, which would alter the load against which the circumscribing smooth muscle shortens when activated. Accordingly, we measured the time course of airway resistance immediately following intravenous methacholine injection in acutely and chronically allergically inflamed mice. We estimated the effective stiffness of the airway wall in these animals by fitting to the airway resistance profiles a computational model of a dynamically narrowing airway embedded in elastic parenchyma. Effective airway wall stiffness was estimated from the model fit and was found not to change from control in either the acute or chronic inflammatory groups. However, the acutely inflamed mice were hyperresponsive compared with controls, which we interpret as reflecting increased delivery of methacholine to the airway smooth muscle through a leaky pulmonary endothelium. These results support the notion that acutely inflamed BALB/c mice represent an animal model of functionally normal airway smooth muscle in a transiently abnormal lung.

scholarly journals Selection of patients with left breast cancer for IMRT with deep inspiration breath-hold technique

2020 ◽  
Vol 61 (3) ◽  
pp. 431-439 ◽  
Author(s):  
Chih-Shen CHANG ◽  
Chia-Hsin CHEN ◽  
Kuo-Chi LIU ◽  
Chia-Sheng HO ◽  
Miao-Fen CHEN
Keyword(s):  
Breast Cancer ◽  
Lung Volume ◽  
Free Breathing ◽  
Target Volume ◽  
Left Breast ◽  
Breath Hold ◽  
Deep Inspiration ◽  
Deep Inspiration Breath Hold ◽  
Total Lung Volume ◽  
The Difference

Abstract The deep inspiration breath-hold (DIBH) technique has been utilized to reduce the cardiac dose in left-sided breast cancer (BC) patients undergoing radiotherapy. Further investigation of the parameters for selecting which patients will benefit most from DIBH is essential. We performed dosimetric comparisons for 21 patients with left-sided BC who had both computed tomography (CT)-based free-breathing (FB) and DIBH plans. The doses to the heart and left anterior descending artery (LAD) and any reduction due to the DIBH technique were analysed. Based on CTFB plans, dosimetric analysis revealed that the irradiation doses to the heart and LAD were significantly correlated with the target volume, the ipsilateral lung volume (ILV) and the total lung volume (TLV). When patients had an ILV ≥ 950 cm3 or a TLV ≥ 2200 cm3, the irradiation doses to the heart and LAD were significantly decreased. Furthermore, the reduction in the mean heart dose (MHD) was correlated to the difference in lung volume between FB and DIBH. The difference in ILV between DIBH and FB of 1.8 indicated that the patients obtained more benefit from the DIBH technique. The data suggest that lung volume (ILV and TLV) measured on a CT-simulation scan and the difference between FB and DIBH could be utilized to help select patients for DIBH.

scholarly journals Airway smooth muscle adapting in dynamic conditions is refractory to the bronchodilator effect of a deep inspiration

2020 ◽  
Vol 318 (2) ◽  
pp. L452-L458
Author(s):  
Morgan Gazzola ◽  
Fatemeh Khadangi ◽  
Marine Clisson ◽  
Jonathan Beaudoin ◽  
Marie-Annick Clavel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Dynamic Environment ◽  
In Vitro Study ◽  
Deep Inspiration ◽  
Isometric Condition ◽  
Time Intervals ◽  
Bronchodilator Effect ◽  
Bronchodilator Response

Airway smooth muscle (ASM) is continuously strained during breathing at tidal volume. Whether this tidal strain influences the magnitude of the bronchodilator response to a deep inspiration (DI) is not clearly defined. The present in vitro study examines the effect of tidal strain on the bronchodilator effect of DIs. ASM strips from sheep tracheas were mounted in organ baths and then subjected to stretches (30% strain), simulating DIs at varying time intervals. In between simulated DIs, the strips were either held at a fixed length (isometric) or oscillated continuously by 6% (length oscillations) to simulate tidal strain. The contractile state of the strips was also controlled by adding either methacholine or isoproterenol to activate or relax ASM, respectively. Although the time-dependent gain in force caused by methacholine was attenuated by length oscillations, part of the acquired force in the oscillating condition was preserved postsimulated DIs, which was not the case in the isometric condition. Consequently, the bronchodilator effect of simulated DIs (i.e., the decline in force postsimulated versus presimulated DIs) was attenuated in oscillating versus isometric conditions. These findings suggest that an ASM operating in a dynamic environment acquired adaptations that make it refractory to the decline in contractility inflicted by a larger strain simulating a DI.

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