Capillary-elastic instabilities of liquid-lined lung airways

To model the competition between capillary and elastic forces in controlling the shape of a small lung airway and its interior liquid lining, we compute the equilibrium configurations of a liquid-lined, externally pressurized, buckled elastic tube. We impose axial uniformity and assume that the liquid wets the tube wall with zero contact angle. Non-zero surface tension has a profound effect on the tube's quasi-steady inflation-deflation characteristics. At low liquid volumes, hysteresis arises through two distinct mechanisms, depending on the buckling wavenumber. Sufficient compression always leads to abrupt and irreversible collapse and flooding of the tube; flooding is promoted by increasing liquid volumes or surface tension. The model captures mechanisms whereby capillary-elastic instabilities can lead to airway closure.     

A hypothesis on the mechanism of trauma of lung tissue subjected to impact load

When a compressive impact load is applied on the chest, as in automobile crash or bomb explosion, the lung may be injured and show evidences of edema and hemorrhage. Since soft tissues have good strength in compression, why does a compression wave cause edema? Our hypothesis is that tensile and shear stresses are induced in the alveolar wall on rebound from compression, and that the maximum principal stress (tensile) may exceed critical values for increased permeability of the epithelium to small solutes, or even fracture. Furthermore, small airways may collapse and trap gas in alveoli at a critical strain, causing traumatic atelectasis. The collapsed airways reopen at a higher strain after the wave passes, during which the expansion of the trapped gas will induce additional tension in the alveolar wall. To test this hypothesis, we made three new experiments: (1), measuring the effect of transient overstretch of the alveolar membrane on the rate of lung weight increase; (2) determining the critical pressure for reopening collapsed airways of rabbit lung subjected to cyclic compression and expansion; (3) cyclic compression of lung with trachea closed. We found that in isolated rabbit lung overstretching increases the rate of edema fluid formation, that the critical strain for airway reopening is higher than that for closing, and that these critical strains are strain-rate dependent, but independent of the state of the trachea, whether it is open or closed. Furthermore, a theoretical analysis is presented to show that the maximum principal (tensile) stress is of the same order of magnitude as the maximum initial compressive stress at certain localities of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of surface-tension-induced epithelial cell damage in a model of pulmonary airway reopening.

Airway collapse and reopening due to mechanical ventilation exerts mechanical stress on airway walls and injures surfactant-compromised lungs. The reopening of a collapsed airway was modeled experimentally and computationally by the progression of a semi-infinite bubble in a narrow fluid-occluded channel. The extent of injury caused by bubble progression to pulmonary epithelial cells lining the channel was evaluated. Counterintuitively, cell damage increased with decreasing opening velocity. The presence of pulmonary surfactant, Infasurf, completely abated the injury. These results support the hypotheses that mechanical stresses associated with airway reopening injure pulmonary epithelial cells and that pulmonary surfactant protects the epithelium from this injury. Computational simulations identified the magnitudes of components of the stress cycle associated with airway reopening (shear stress, pressure, shear stress gradient, or pressure gradient) that may be injurious to the epithelial cells. By comparing these magnitudes to the observed damage, we conclude that the steep pressure gradient near the bubble front was the most likely cause of the observed cellular damage.     

The role of ventilation frequency in airway reopening

Inhomogeneously compliant lungs need special treatment during ventilation as they are often affected by respiratory insufficiency which is frequently caused by a regional collapse of the airways. To treat respiratory insufficiency atelectatic areas have to be recruited. Beside conventional mechanical ventilation, high-frequency oscillatory ventilation (HFOV) is an efficient method for airway reopening. Using a transparent in-vitro model of the human lung the influence of varying frequencies on the reopening behavior of atelectatic regions is investigated for volume controlled ventilation. The experiments show that higher ventilation frequencies at constant tidal volume enhance the probability of successful reopening of collapsed lung regions and thus, lead to a more homogeneous distribution of air within the lung. This effect can be attributed (i) to larger flow velocities and thus larger pressure losses in the free pathways as the ventilation frequency increases and (ii) to higher inertia effects. In consequence, the static pressure in the branches above the atelectatic regions increases until it reaches a level at which recruitment is achieved.     

Compliance of peripheral airways deduced from morphometry.

Insights into airway mechanics were sought by applying morphometric techniques to rabbit lungs fixed at several lung recoil pressures. Rabbits were treated with either nebulized carbachol followed by iv administration of carbachol or with saline solution (sham). The lungs were held at one of six values of positive end-expiratory pressure (PEEP; 10, 7, 4, 2, 0, and -4 cmH(2)O) while the animal was killed and formalin was circulated through the lungs. The lungs were removed and left in a bath of formalin for 24 h. Standard airway morphometric measurements were made on membranous bronchiole slices taken from representative blocks of tissue. Reductions in PEEP produced the expected reductions in lumen area in the carbachol-treated airways but not in the sham-treated airways for PEEP > 2 cmH(2)O. Sham-treated airways remained more open than expected until they collapsed into an oval shape at PEEPs between 4 and 2 cmH(2)O. The carbachol-treated airways exhibited this behavior at PEEP = -4 cmH(2)O. The smallest airways, which had relatively thicker walls, collapsed less than larger airways. We postulate that this behavior implies that peribronchial stress is greater than lumen pressure on collapse into the oval shape. Resistance to buckling increases with the thickness-to-radius ratio of the airway wall, which explains why the smallest airways are the most open. The development of epithelial folds appeared to follow the theoretical prediction of a previous study (Lambert RK, Codd SL, Alley MR, and Pack RJ. J Appl Physiol 77: 1206-1216, 1994).     

下呼吸道重开的生物流体力学研究:实验模拟

实验模拟了受阻塞肺下呼吸道重开的生物力学问题。呼吸是玻璃直圆管,以具有生物流体性质的机油作为阻塞液。实验给同了在压强差作用下阻塞液柱前陈面以及主粘液柱气泡前阵面的位置和速度曲线。结果表明,它们受外加压强,管直径,阻塞液以及初始阻塞液长度的影响。较高的外加中、阻塞液粘度较你攻管径较粗有利于呼吸道的重开。     

Direct numerical simulation of expiratory crackles: Relationship between airway closure dynamics and acoustic fluctuations

This paper investigates the relationship between airway closure dynamics and acoustic fluctuations in expiratory crackles using direct numerical simulation. A unified mathematical model is proposed to deal with flow in an airway, elastic deformation of the airway wall, surface tension driven motion of the liquid film that lines the airway, and their acoustic fluctuations because of material compressibility. Airway closure is induced by increasing the surrounding pressure, then the source of the pressure fluctuations is measured over time. Our results show that the airway closure occurs suddenly because of a bridge formation of the liquid film, and high energy transfer occurs between the kinetic energy, the surface energy of the liquid interface, and the elastic energy of the airway wall, invoking a large acoustic fluctuation that causes the expiratory crackles. Nonlinear behavior is observed in terms of the airway wall stiffness; the dynamic motion of the airway closure becomes moderate and both the energy transfer and acoustic fluctuations are dramatically reduced with an increase in airway wall stiffness.     

Surfactant transport over airway liquid lining of nonuniform depth

Numerous effects (e.g., airway wall buckling, gravity, airway curvature, capillary instabilities) give rise to nonuniformities in the depth of the liquid lining of peripheral lung airways. The effects of such thickness variations on the unsteady spreading of a surfactant monolayer along an airway are explored theoretically here. Flow-induced film deformations are shown to have only a modest influence on spreading rates, motivating the use of a simplified model in which the liquid-lining depth is prescribed and the monolayer concentration satisfies a spatially inhomogeneous nonlinear diffusion equation. Two generic situations are considered: spreading along a continuous annular liquid lining of nonuniform depth, and spreading along a rivulet that wets the airway wall with zero contact angle. In both cases, transverse averaging at large times yields a one-dimensional approximation of axial spreading that is valid for the majority of the monolayer. However, a localized monolayer remains persistently two dimensional in a region at its leading edge having axial length scales comparable to the length scale of transverse depth variation. It is also shown how the transverse spreading of a monolayer may be arrested as it approaches a static contact line at the edge of a rivulet. Implications for Surfactant Replacement Therapy are discussed.     

A finite-element model of tracheal collapse

The trachea has been approximated by an appropriate finite-element model. The three-dimensional equilibrium problems set by the tracheal deformation under various stresses have been solved using a convenient augmented Lagrangian functional. The dimensions were obtained from human tracheae. Mechanical constants for the anatomic components were calculated from the stress-strain relationships. The compressive narrowing is essentially due to the invagination of the posterior membrane in the tracheal lumen for transmural pressures down to -7 kPa. A surface of contact between the membranous wall and the lateral walls appears when the transmural pressure equals -6 kPa. The transmural pressure-area relationship is sigmoidal with a compliance equal to 0.08 kPa-1 for a transmural pressure of -2 kPa. The tracheal collapse is greater when the material constants of the membranous wall decrease or when the tracheal segment is subjected to a longitudinal tension. A slight flexion of the trachea induces an asymmetric deformation.     

Effect of airway surface liquid on the forces on the pharyngeal wall: Experimental fluid–structure interaction study

Obstructive sleep apnoea syndrome (OSAS) is a breathing disorder with a multifactorial etiology. The respiratory epithelium is lined with a thin layer of airway surface liquid preventing interactions between the airflow and epithelium. The effect of the liquid lining in OSAS pathogenesis remains poorly understood despite clinical research. Previous studies have shown that the physical properties of the airway surface liquid or altered stimulation of the airway mechanoreceptors could alleviate or intensify OSAS; however, these studies do not provide a clear physical interpretation. To study the forces transmitted from the airflow to the liquid-lined compliant wall and to discuss the effects of the airway surface liquid properties on the stimulation of the mechanoreceptors, a novel and simplified experimental system mimicking the upper airway fundamental characteristics (i.e., liquid-lined compliant wall and complex unsteady airflow features) was constructed. The fluctuating force on the compliant wall was reduced through a damping mechanism when the liquid film thickness and/or the viscosity were increased. Conversely, the liquid film damping was reduced when the surface tension decreased. Based on the experimental data, empirical correlations were developed to predict the damping potential of the liquid film. In the future, this will enable us to extend the existing computational fluid–structure interaction simulations of airflow in the human upper airway by incorporating the airway surface liquid effect without adopting two-phase flow interface tracking methods. Furthermore, the experimental system developed in this study could be used to investigate the fundamental principles of the complex once/twice-coupled physical phenomena.     

Cell deformation at the air-liquid interface induces Ca2+-dependent ATP release from lung epithelial cells

Extracellular nucleotides regulate mucociliary clearance in the airways and surfactant secretion in alveoli. Their release is exquisitely mechanosensitive and may be induced by stretch as well as airflow shear stress acting on lung epithelia. We hypothesized that, in addition, tension forces at the air-liquid interface (ALI) may contribute to mechanosensitive ATP release in the lungs. Local depletion of airway surface liquid, mucins, and surfactants, which normally protect epithelial surfaces, facilitate such release and trigger compensatory mucin and fluid secretion processes. In this study, human bronchial epithelial 16HBE14o(-) and alveolar A549 cells were subjected to tension forces at the ALI by passing an air bubble over the cell monolayer in a flow-through chamber, or by air exposure while tilting the cell culture dish. Such stimulation induced significant ATP release not involving cell lysis, as verified by ethidium bromide staining. Confocal fluorescence microscopy disclosed reversible cell deformation in the monolayer part in contact with the ALI. Fura 2 fluorescence imaging revealed transient intracellular Ca(2+) elevation evoked by the ALI, which did not entail nonspecific Ca(2+) influx from the extracellular space. ATP release was reduced by ～40 to ～90% from cells loaded with the Ca(2+) chelator BAPTA-AM and was completely abolished by N-ethylmalemide (1 mM). These experiments demonstrate that in close proximity to the ALI, surface tension forces are transmitted directly on cells, causing their mechanical deformation and Ca(2+)-dependent exocytotic ATP release. Such a signaling mechanism may contribute to the detection of local deficiency of airway surface liquid and surfactants on the lung surface.     

Xylem wall collapse in water-stressed pine needles

Wall reinforcement in xylem conduits is thought to prevent wall implosion by negative pressures, but direct observations of xylem geometry during water stress are still largely lacking. In this study, we have analyzed the changes in xylem geometry during water stress in needles of four pine species (Pinus spp.). Dehydrated needles were frozen with liquid nitrogen, and xylem cross sections were observed, still frozen, with a cryo-scanning electron microscope and an epifluorescent microscope. Decrease in xylem pressure during drought provoked a progressive collapse of tracheids below a specific threshold pressure (P(collapse)) that correlates with the onset of cavitation in the stems. P(collapse) was more negative for species with smaller tracheid diameter and thicker walls, suggesting a tradeoff between xylem efficiency, xylem vulnerability to collapse, and the cost of wall stiffening. Upon severe dehydration, tracheid walls were completely collapsed, but lumens still appeared filled with sap. When dehydration proceeded further, tracheids embolized and walls relaxed. Wall collapse in dehydrated needles was rapidly reversed upon rehydration. We discuss the implications of this novel hydraulic trait on the xylem function and on the understanding of pine water relations.     

Pulmonary surfactant function studied with the pulsating bubble surfactometer (PBS) and the capillary surfactometer (CS)

Two instruments, the pulsating bubble surfactometer (PBS) and the capillary surfactometer (CS), were constructed for a study of pulmonary surfactant's physical properties. The instruments study spherical surfaces as in alveoli (PBS) and cylindrical surfaces as in terminal conducting airways (CS). Phospholipids, pulmonary surfactant's main components, are amphiphilic and, therefore, spontaneously form a film at air-liquid interfaces. When the film in the PBS is compressed to a reduced area during 'expiration', the molecules come closer together. Thereby, a high surface pressure develops, causing surface tension to be reduced more than bubble radius. If these conditions, observed with the PBS are analogous in lungs, alveolar stability would be promoted. The CS was developed for a study of how surfactant has ability to maintain patency of narrow conducting airways. Provided adsorption is extremely fast, a surfactant film will line the terminal conducting airway as soon as liquid blocking the airway has been extruded. During expiration that film will develop high surface pressure (=low surface tension). This will counteract the tendency for liquid to accumulate in the airway's most narrow section. If surfactant is dysfunctioning, liquid is likely to accumulate and block terminal airways. Airway resistance would then increase, causing FEV(1) to be reduced.     

Factors influencing regional patency and configuration of the human infant upper airway

To study factors influencing patency and configuration of the upper airway, we studied 11 infant cadavers using endoscopy and photography. In most cases, studies were performed shortly after death. The naso-, oro-, and hypopharynx and the larynx were studied. The upper airway was sealed at the nose and mouth so that transmural airway pressure could be raised or lowered. As pressure was lowered airway closure was seen in each of the four regions studied. With respect to closing pressure, the oropharynx was the most compliant region and the larynx the least compliant. In the naso-, oro-, and hypopharynx, lowering the transmural pressure was associated with inward movement of the anterior, posterior, and lateral airway walls. In the larynx, closure occurred by vocal cord opposition in the midline. Tension applied to the genioglossus and geniohyoid tongue muscles had an effect opposite to that of airway suction, causing a more or less symmetrical dilation of the naso- and oropharynx. When the airway was closed, additional tension was needed to produce airway reopening, suggesting that adhesion forces act to maintain airway closure. Neck flexion caused pharyngeal closure, and neck extension caused pharyngeal dilation. Secretions adherent to the walls of the airway visibly narrowed its lumen. The relevance of these findings for the obstructive sleep apnea and laryngomalacia syndromes is discussed.     

Effects of surface tension and viscosity on airway reopening

We studied airway opening in a benchtop model intended to mimic bronchial walls held in apposition by airway lining fluid. We measured the relationship between the airway opening velocity (U) and the applied airway opening pressure in thin-walled polyethylene tubes of different radii (R) using lining fluids of different surface tensions (gamma) and viscosities (mu). Axial wall tension (T) was applied to modify the apparent wall compliance characteristics, and the lining film thickness (H) was varied. Increasing mu or gamma or decreasing R or T led to an increase in the airway opening pressures. The effect of H depended on T: when T was small, opening pressures increased slightly as H was decreased; when T was large, opening pressure was independent of H. Using dimensional analysis, we found that the relative importance of viscous and surface tension forces depends on the capillary number (Ca = microU/gamma). When Ca is small, the opening pressure is approximately 8 gamma/R and acts as an apparent "yield pressure" that must be exceeded before airway opening can begin. When Ca is large (Ca greater than 0.5), viscous forces add appreciably to the overall opening pressures. Based on these results, predictions of airway opening times suggest that airway closure can persist through a considerable portion of inspiration when lining fluid viscosity or surface tension are elevated.     

Effect of surface tension of mucosal lining liquid on upper airway mechanics in anesthetized humans.

Upper airway (UA) patency may be influenced by surface tension (gamma) operating within the (UAL). We examined the role of gamma of UAL in the maintenance of UA patency in eight isoflurane-anesthetized supine human subjects breathing via a nasal mask connected to a pneumotachograph attached to a pressure delivery system. We evaluated 1). mask pressure at which the UA closed (Pcrit), 2). UA resistance upstream from the site of UA collapse (RUS), and 3). mask pressure at which the UA reopened (Po). A multiple pressure-transducer catheter was used to identify the site of airway closure (velopharyngeal in all subjects). UAL samples (0.2 microl) were collected, and the gamma of UAL was determined by using the "pull-off force" technique. Studies were performed before and after the intrapharyngeal instillation of 5 ml of exogenous surfactant (Exosurf, Glaxo Smith Kline). The gamma of UAL decreased from 61.9 +/- 4.1 (control) to 50.3 +/- 5.0 mN/m (surfactant; P < 0.02). Changes in Po, RUS, and Po - Pcrit (change = control - surfactant) were positively correlated with changes in gamma (r2 > 0.6; P < 0.02) but not with changes in Pcrit (r2 = 0.4; P > 0.9). In addition, mean peak inspiratory airflow (no flow limitation) significantly increased (P < 0.04) from 0.31 +/- 0.06 (control) to 0.36 +/- 0.06 l/s (surfactant). These findings suggest that gamma of UAL exerts a force on the UA wall that hinders airway opening. Instillation of exogenous surfactant into the UA lowers the gamma of UAL, thus increasing UA patency and augmenting reopening of the collapsed airway.     

The effects of wall thickness, axial strain and end proximity on the pressure-area relation of collapsible tubes

Segments of silicone rubber tube were suspended between rigid pipes and subjected to slowly varying transmural pressure covering a range from slight distension to collapse with osculation. The local inside cross-sectional area at a chosen axial site was simultaneously measured via catheter by an electrical impedance method. Pressure-area relations were recorded thus at various axial sites, under varying conditions of axial tube wall tension, in tubes of two different wall thickness (0.3 and 0.4 of mean radius). Unsupported tube segment length was also varied by means of an insert device. The relations were used to calculate the variation of wave velocity with area according to Young's equation. First opposite wall contact during collapse was shown to occur at a smaller fraction of undistended circular cross-sectional area than in the thin-walled tubes investigated previously by others.     

Inspirational airflow patterns in deviated noses: a numerical study

This study attempts to evaluate the effects of deviation of external nose to nasal airflow patterns. Four typical subjects were chosen for model reconstruction based on computed tomography images of undeviated, S-shaped deviated, C-shaped deviated and slanted deviated noses. To study the hypothetical influence of deviation of external nasal wall on nasal airflow (without internal blockage), the collapsed region along the turbinate was artificially reopened in all the three cases with deviated noses. Computational fluid dynamics simulations were carried out in models of undeviated, original deviated and reopened nasal cavities at both flow rates of 167 and 500 ml/s. The shape of the anterior nasal roof was found to be collapsed on one side of the nasal airways in all the deviated noses. High wall shear stress region was found around the collapsed anterior nasal roof. The nasal resistances in cavities with deviated noses were considerably larger than healthy nasal cavity. Patterns of path-line distribution and wall shear stress distribution were similar between original deviated and reopened models. In conclusion, the deviation of an external nose is associated with the collapse of one anterior nasal roof. The crooked external nose induced a larger nasal resistance compared to the undeviated case, while the internal blockage of the airway along the turbinates further increased it.