Individual Alveoli Research Articles

High resolution fluorescence imaging of the alveolar scaffold as a novel tool to assess lung injury

Acute lung injury (ALI) represents an aetiologically diverse form of pulmonary damage. Part of the assessment and diagnosis of ALI depends on skilled observer-based scoring of brightfield microscopy tissue sections. Although this readout is sufficient to determine gross alterations in tissue structure, its categorical scores lack the sensitivity to describe more subtle changes in lung morphology. To generate a more sensitive readout of alveolar perturbation we carried out high resolution immunofluorescence imaging on 200 μm lung vibratome sections from baseline and acutely injured porcine lung tissue, stained with a tomato lectin, Lycopersicon Esculentum Dylight-488. With the ability to resolve individual alveoli along with their inner and outer wall we generated continuous readouts of alveolar wall thickness and circularity. From 212 alveoli traced from 10 baseline lung samples we established normal distributions for alveolar wall thickness (27.37; 95% CI [26.48:28.26]) and circularity (0.8609; 95% CI [0.8482:0.8667]) in healthy tissue. Compared to acutely injured lung tissue baseline tissue exhibited a significantly lower wall thickness (26.86 ± 0.4998 vs 50.55 ± 4.468; p = 0.0003) and higher degree of circularityϕ≤ (0.8783 ± 0.01965 vs 0.4133 ± 0.04366; p < 0.0001). These two components were subsequently combined into a single more sensitive variable, termed the morphological quotient (MQ), which exhibited a significant negative correlation (R2 = 0.9919, p < 0.0001) with the gold standard of observer-based scoring. Through the utilisation of advanced light imaging we show it is possible to generate sensitive continuous datasets describing fundamental morphological changes that arise in acute lung injury. These data represent valuable new analytical tools that can be used to precisely benchmark changes in alveolar morphology both in disease/injury as well as in response to treatment/therapy.

Remodeling of the Blood-Air Barrier Components in the Landscape of the Far North

The aim of the study was to evaluate the structural and functional changes in the components of the respiratory department of the lungs during the stay of experimental animals in the conditions of the Far North.Material and methods. The experiments were carried out on white outbred male rats 140–160 g by mass on the 7-, 15- and 30th days of stay in the conditions of northern latitudes – in Kogalym (62° 26′ N and 74° 48′ E). The structural components of the blood-air barrier were studied using light microscopy, transmission and scanning electron microscopy. The thickness of cytoplasmic processes of type I pneumocytes, cytoplasmic processes of endotheliocytes of capillaries and basement membranes was determined.Results. During all periods of stay of animals in the conditions of the Far North, thickening of the cytoplasmic processes of type I pneumocytes was noted, while the thickness of the cytoplasmic processes of endotheliocytes was significantly increased on the 7th day (p&lt;0,032) and reached control values by the 15th day. During these periods, interstitial edema of the walls and transudate exudation in the lumen of the alveoli, multivesicular and osmophilic lamellar bodies in the cytoplasm of type II pneumocytes were observed, followed by surfactant release into the lumen of the alveoli according to the merocrine type. Later, in the conditions of the Far North, there was a tendency to decrease the main indicators of the blood-air barrier. There were single blood cells in the lumen of the alveoli, Kohn pores between the alveoli, and the merocrine type of surfactant release into the lumen of the alveoli was preserved in type II pneumocytes.Conclusion. As a result of the research, it was established that in the early periods of the animals' stay in the conditions of the Far North, there is an increase in the main components of blood-air barrier (cytoplasmic processes of type I pneumocytes, basal membranes and capillary endotheliocytes). In the early stages of animal adaptation, the phenomena of interstitial edema of the walls with transudation into their lumen are noted in individual alveoli. By the 30th day, there is a tendency to decrease the main indicators of the blood-air barrier compared to previous terms, but they do not reach the control values; the surfactant yield in the apical part of type II pneumocytes by the merocrine type is preserved.

Predicting alveolar ventilation heterogeneity in pulmonary fibrosis using a non-uniform polyhedral spring network model.

Pulmonary Fibrosis (PF) is a deadly disease that has limited treatment options and is caused by excessive deposition and cross-linking of collagen leading to stiffening of the lung parenchyma. The link between lung structure and function in PF remains poorly understood, although its spatially heterogeneous nature has important implications for alveolar ventilation. Computational models of lung parenchyma utilize uniform arrays of space-filling shapes to represent individual alveoli, but have inherent anisotropy, whereas actual lung tissue is isotropic on average. We developed a novel Voronoi-based 3D spring network model of the lung parenchyma, the Amorphous Network, that exhibits more 2D and 3D similarity to lung geometry than regular polyhedral networks. In contrast to regular networks that show anisotropic force transmission, the structural randomness in the Amorphous Network dissipates this anisotropy with important implications for mechanotransduction. We then added agents to the network that were allowed to carry out a random walk to mimic the migratory behavior of fibroblasts. To model progressive fibrosis, agents were moved around the network and increased the stiffness of springs along their path. Agents migrated at various path lengths until a certain percentage of the network was stiffened. Alveolar ventilation heterogeneity increased with both percent of the network stiffened, and walk length of the agents, until the percolation threshold was reached. The bulk modulus of the network also increased with both percent of network stiffened and path length. This model thus represents a step forward in the creation of physiologically accurate computational models of lung tissue disease.

A new species of Comahuesuchus Bonaparte, 1991 (Crocodyliformes: Notosuchia) from the Upper Cretaceous of Neuquén, Lake Barreales, Patagonia, Argentina.

Notosuchian crocodyliforms were major components of the South American Cretaceous biota and, for over 125 years, paleontological fieldwork in this continent recovered several well-preserved fossils of these animals. They are largely recognized for terrestrial life and specialized feeding habits, frequently presenting bizarre taxa such as Comahuesuchus. A new species, Comahuesuchus bonapartei n. sp. (MUCPv 597; cast MN), is described from geological strata of Sierra Barrosa Formation (Upper Turonian) and Portezuelo Formation (Lower Coniacian) of Lake Barreales, Patagonia, Argentina. The new fossil comprises a right dentary bone that shares important and unique anatomical features with specimens of Comahuesuchus brachybuccalis, such as the presence of a well-marked shelf on the lateral surface of the bone; a flat, low, and wide mandibular symphysis; an enlarged, labiolingually compressed caniniform tooth at caudal position in the dentary; the presence of serrated mesial and distal carinae in the caniniform with a faceted labial surface, and the absence or extremely reduction in number of the postcaniniform dentition. C. bonapartei differs from C. brachybuccalis in having individual dentary alveoli, rather a dentition set in groove. Phylogenetic analyses support a sister-relationship between both species, which are well nested within notosuchians.

Alveolus analysis: a web browser-based tool to analyze lung intravital microscopy

BackgroundAcute lung injury and the acute respiratory distress syndrome are characterized by pulmonary inflammation, reduced endothelial barrier integrity and filling of the alveolar space with protein rich edema fluid and infiltrating leukocytes. Animal models are critical to uncovering the pathologic mechanisms of this devastating syndrome. Intravital imaging of the intact lung via two-photon intravital microscopy has proven a valuable method to investigate lung injury in small rodent models through characterization of inflammatory cells and vascular changes in real time. However, respiratory motion complicates the analysis of these time series images and requires selective data extraction to stabilize the image. Consequently, analysis of individual alveoli may not provide a complete picture of the integrated mechanical, vascular and inflammatory processes occurring simultaneously in the intact lung. To address these challenges, we developed a web browser-based visualization application named Alveolus Analysis to process, analyze and graphically display intravital lung microscopy data.ResultsThe designed tool takes raw temporal image data as input, performs image preprocessing and feature extraction offline, and visualizes the extracted information in a web browser-based interface. The interface allows users to explore multiple experiments in three panels corresponding to different levels of detail: summary statistics of alveolar/neutrophil behavior, characterization of alveolar dynamics including lung edema and inflammatory cells at specific time points, and cross-experiment analysis. We performed a case study on the utility of the visualization with two members or our research team and they found the tool useful because of its ability to preprocess data consistently and visualize information in a digestible and informative format.ConclusionsApplication of our software tool, Alveolus Analysis, to intravital lung microscopy data has the potential to enhance the information gained from these experiments and provide new insights into the pathologic mechanisms of inflammatory lung injury.

New insight into air flow distribution in alveoli based on air- and saline-filled lungs

Understanding flow distributions in human lungs has attracted significant attention since the last few decades. However, there are still large discrepancies between different studies in the distribution of air flow into alveoli at different generations of bifurcation. In this study, a new method has been developed to calculate expansion ratio of alveoli and ratio of alveolar to ductal flow rate at different generations for air- and saline-filled lungs. The effects of alveolar number, breathing period, lung tidal volume, and surface tension are examined. It is found that the expansion ratio of alveoli varies significantly at different generations in the saline-filled lungs. For the air-filled lung, the expansion ratio of individual alveolus remains constant for different generations. The current study provides new data on the flow rate ratios which is critical for understanding flow distributions and flow behaviors in alveoli. Surface tension in alveoli and alveolar number has obvious effects on the value of flow ratio. The current study sheds new light into the flow behavior in lungs and lays the foundation for detailed study on flow and particle transport characteristics in human lungs.

Simulation of Airflow in an Idealized Emphysematous Human Acinus.

Emphysema is the permanent enlargement of air spaces in the respiratory regions of the lung due to destruction of the inter-alveolar septa. The progressive coalescence of alveoli and alveolar ducts into larger airspaces leads to the disruption of normal airway wall motion and airflow rates within the pulmonary acinus. To contribute to the understanding of the individual effects of emphysema during its earliest stages, computational fluid dynamics (CFD) simulations of airflow in mathematically derived models of the pulmonary acinus were performed. The here generated computational domain consists of two generations of alveolar ducts within the pulmonary acinus, with alveolar geometries approximated as closely packed, 14-sided polygons. Physiologically realistic airflow rates and wall motions were used to study airflow patterns within subsequent generations of alveolar ducts during the inspiratory and expiratory phases of the breathing cycle. The effects of progressive emphysema on the airway wall motion and flow rates were simulated by sequentially removing all alveolar septa within each alveolar duct. Parametric studies were presented to independently assess the relative influence of progressive septal destruction of airway motion and flow rates. The results illustrate that septal destruction lowers the flow resistance through the alveolar ducts but has little influence on the mass transport of oxygen into the alveoli. Septal destruction has a net effect on the flow field by favoring the development of recirculatory flow patterns in individual alveoli.

The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro.

IntroductionGenome-Wide Association Studies have identified associations between lung function measures and Chronic Obstructive Pulmonary Disease (COPD) and chromosome region 6p21 containing the gene for the Advanced Glycation End Product Receptor (AGER, encoding RAGE). We aimed to (i) characterise RAGE expression in the lung, (ii) identify AGER transcripts, (iii) ascertain if SNP rs2070600 (Gly82Ser C/T) is associated with lung function and serum sRAGE levels and (iv) identify whether the Gly82Ser variant is functionally important in altering sRAGE levels in an airway epithelial cell model.MethodsImmunohistochemistry was used to identify RAGE protein expression in 26 human tissues and qPCR was used to quantify AGER mRNA in lung cells. Gene expression array data was used to identify AGER expression during lung development in 38 fetal lung samples. RNA-Seq was used to identify AGER transcripts in lung cells. sRAGE levels were assessed in cells and patient serum by ELISA. BEAS2B-R1 cells were transfected to overexpress RAGE protein with either the Gly82 or Ser82 variant and sRAGE levels identified.ResultsImmunohistochemical assessment of 6 adult lung samples identified high RAGE expression in the alveoli of healthy adults and individuals with COPD. AGER/RAGE expression increased across developmental stages in human fetal lung at both the mRNA (38 samples) and protein levels (20 samples). Extensive AGER splicing was identified. The rs2070600T (Ser82) allele is associated with higher FEV1, FEV1/FVC and lower serum sRAGE levels in UK smokers. Using an airway epithelium model overexpressing the Gly82 or Ser82 variants we found that HMGB1 activation of the RAGE-Ser82 receptor results in lower sRAGE production.ConclusionsThis study provides new information regarding the expression profile and potential role of RAGE in the human lung and shows a functional role of the Gly82Ser variant. These findings advance our understanding of the potential mechanisms underlying COPD particularly for carriers of this AGER polymorphism.

Synchrotron X-ray imaging of pulmonary alveoli in respiration in live intact mice.

Despite nearly a half century of studies, it has not been fully understood how pulmonary alveoli, the elementary gas exchange units in mammalian lungs, inflate and deflate during respiration. Understanding alveolar dynamics is crucial for treating patients with pulmonary diseases. In-vivo, real-time visualization of the alveoli during respiration has been hampered by active lung movement. Previous studies have been therefore limited to alveoli at lung apices or subpleural alveoli under open thorax conditions. Here we report direct and real-time visualization of alveoli of live intact mice during respiration using tracking X-ray microscopy. Our studies, for the first time, determine the alveolar size of normal mice in respiration without positive end expiratory pressure as 58 ± 14 (mean ± s.d.) μm on average, accurately measured in the lung bases as well as the apices. Individual alveoli of normal lungs clearly show heterogeneous inflation from zero to ~25% (6.7 ± 4.7% (mean ± s.d.)) in size. The degree of inflation is higher in the lung bases (8.7 ± 4.3% (mean ± s.d.)) than in the apices (5.7 ± 3.2% (mean ± s.d.)). The fraction of the total tidal volume allocated for alveolar inflation is 34 ± 3.8% (mean ± s.e.m). This study contributes to the better understanding of alveolar dynamics and helps to develop potential treatment options for pulmonary diseases.

Instability of misoprostol tablets stored outside the blister: a potential serious concern for clinical outcome in medical abortion.

IntroductionMisoprostol (Cytotec) is recognised to be effective for many gynaecological indications including termination of pregnancy, management of miscarriage and postpartum haemorrhage. Although not licensed for such indications, it has been used for these purposes by millions of women throughout the world. Misoprostol tablets are most often packaged as multiple tablets within an aluminium strip, each within an individual alveolus. When an alveolus is opened, tablets will be exposed to atmospheric conditions.ObjectiveTo compare the pharmaco technical characteristics (weight, friability), water content, misoprostol content and decomposition product content (type A misoprostol, type B misoprostol and 8-epi misoprostol) of misoprostol tablets Cytotec (Pfizer) exposed to air for periods of 1 hour to 720 hours (30 days), to those of identical non exposed tablets.MethodsFour hundred and twenty (420) tablets of Cytotec (Pfizer) were removed from their alveoli blister and stored at 25°C/60% relative humidity. Water content, and misoprostol degradation products were assayed in tablets exposed from 1 to 720 hours (30 days). Comparison was made with control tablets (N = 60) from the same batch stored in non-damaged blisters. Statistical analyses were carried out using Fisher’s exact test for small sample sizes.ResultsBy 48 hours, exposed tablets demonstrated increased weight (+4.5%), friability (+1 300%), and water content (+80%) compared to controls. Exposed tablets also exhibited a decrease in Cytotec active ingredient dosage (−5.1% after 48 hours) and an increase in the inactive degradation products (+25% for type B, +50% for type A and +11% for 8-epi misoprostol after 48 hours) compared to controls.ConclusionExposure of Cytotec tablets to ‘typical’ European levels of air and humidity results in significant time-dependent changes in physical and biological composition that could impact adversely upon clinical efficacy. Health professionals should be made aware of the degradation of misoprostol with inappropriate storage of misoprostol tablets.

Optical coherence tomography in respiratory science and medicine: from airways to alveoli.

Optical coherence tomography is a rapidly maturing optical imaging technology, enabling study of the in vivo structure of lung tissue at a scale of tens of micrometers. It has been used to assess the layered structure of airway walls, quantify both airway lumen caliber and compliance, and image individual alveoli. This article provides an overview of the technology and reviews its capability to provide new insights into respiratory disease.

Living a healthier lifestyle.

The roles of diet, activity, and exercise have long been recognized as essential to a healthy lifestyle. As Plato stated, “Lack of activity destroys the good condition of every human being, while movement and methodical physical exercise save it and preserve it.” In his Physiology is Medicine

Four-dimensional visualization of subpleural alveolar dynamics in vivo during uninterrupted mechanical ventilation of living swine.

Pulmonary alveoli have been studied for many years, yet no unifying hypothesis exists for their dynamic mechanics during respiration due to their miniature size (100-300 μm dimater in humans) and constant motion, which prevent standard imaging techniques from visualizing four-dimensional dynamics of individual alveoli in vivo. Here we report a new platform to image the first layer of air-filled subpleural alveoli through the use of a lightweight optical frequency domain imaging (OFDI) probe that can be placed upon the pleura to move with the lung over the complete range of respiratory motion. This device enables in-vivo acquisition of four-dimensional microscopic images of alveolar airspaces (alveoli and ducts), within the same field of view, during continuous ventilation without restricting the motion or modifying the structure of the alveoli. Results from an exploratory study including three live swine suggest that subpleural alveolar air spaces are best fit with a uniform expansion (r (2) = 0.98) over a recruitment model (r (2) = 0.72). Simultaneously, however, the percentage change in volume shows heterogeneous alveolar expansion within just a 1 mm x 1 mm field of view. These results signify the importance of four-dimensional imaging tools, such as the device presented here. Quantification of the dynamic response of the lung during ventilation may help create more accurate modeling techniques and move toward a more complete understanding of alveolar mechanics.

Murine pulmonary acinar mechanics during quasi-static inflation using synchrotron refraction-enhanced computed tomography

We visualized pulmonary acini in the core regions of the mouse lung in situ using synchrotron refraction-enhanced computed tomography (CT) and evaluated their kinematics during quasi-static inflation. This CT system (with a cube voxel of 2.8 μm) allows excellent visualization of not just the conducting airways, but also the alveolar ducts and sacs, and tracking of the acinar shape and its deformation during inflation. The kinematics of individual alveoli and alveolar clusters with a group of terminal alveoli is influenced not only by the connecting alveolar duct and alveoli, but also by the neighboring structures. Acinar volume was not a linear function of lung volume. The alveolar duct diameter changed dramatically during inflation at low pressures and remained relatively constant above an airway pressure of ∼8 cmH2O during inflation. The ratio of acinar surface area to acinar volume indicates that acinar distension during low-pressure inflation differed from that during inflation over a higher pressure range; in particular, acinar deformation was accordion-like during low-pressure inflation. These results indicated that the alveoli and duct expand differently as total acinar volume increases and that the alveolar duct may expand predominantly during low-pressure inflation. Our findings suggest that acinar deformation in the core regions of the lung is complex and heterogeneous.

Tracking X-ray microscopy for alveolar dynamics in live intact mice

Here we report a tracking X-ray microscopy (TrXM) as a novel methodology by using upper right lung apices alveoli in live intact mice. By enabling tracking of individual alveolar movements during respiration, TrXM identifies alveolar dynamics: individual alveoli in the upper lung apices show a small size increment as 4.9 ± 0.4% (mean ± s.e.m.) during respiration while their shapes look almost invariant. TrXM analysis in alveolar dynamics would be significant for better understanding of alveolar-based diseases, for instance, ventilator induced lung injury (VILI) in acute respiratory distress syndrome (ARDS).

The Simultaneous Role of an Alveolus as Flow Mixer and Flow Feeder for the Deposition of Inhaled Submicron Particles

In an effort to understand the fate of inhaled submicron particles in the small sacs, or alveoli, comprising the gas-exchange region of the lung, we calculated the flow in three-dimensional (3D) rhythmically expanding models of alveolated ducts. Since convection toward the alveolar walls is a precursor to particle deposition, it was the goal of this paper to investigate the streamline maps' dependence upon alveoli location along the acinar tree. On the alveolar midplane, the recirculating flow pattern exhibited closed streamlines with a stagnation saddle point. Off the midplane we found no closed streamlines but nested, funnel-like, spiral, structures (reminiscent of Russian nesting dolls) that were directed towards the expanding walls in inspiration, and away from the contracting walls in expiration. These nested, funnel-like, structures were surrounded by air that flowed into the cavity from the central channel over inspiration and flowed from the cavity to the central channel over expiration. We also found that fluid particle tracks exhibited similar nested funnel-like spiral structures. We conclude that these unique alveolar flow structures may be of importance in enhancing deposition. In addition, due to inertia, the nested, funnel-like, structures change shape and position slightly during a breathing cycle, resulting in flow mixing. Also, each inspiration feeds a fresh supply of particle-laden air from the central channel to the region surrounding the mixing region. Thus, this combination of flow mixer and flow feeder makes each individual alveolus an effective mixing unit, which is likely to play an important role in determining the overall efficiency of convective mixing in the acinus.

Static and dynamic imaging of alveoli using optical coherence tomography needle probes

Imaging of alveoli in situ has for the most part been infeasible due to the high resolution required to discern individual alveoli and limited access to alveoli beneath the lung surface. In this study, we present a novel technique to image alveoli using optical coherence tomography (OCT). We propose the use of OCT needle probes, where the distal imaging probe has been miniaturized and encased within a hypodermic needle (as small as 30-gauge, outer diameter 310 μm), allowing insertion deep within the lung tissue with minimal tissue distortion. Such probes enable imaging at a resolution of ∼12 μm within a three-dimensional cylindrical field of view with diameter ∼1.5 mm centered on the needle tip. The imaging technique is demonstrated on excised lungs from three different species: adult rats, fetal sheep, and adult pigs. OCT needle probes were used to image alveoli, small bronchioles, and blood vessels, and results were matched to histological sections. We also present the first dynamic OCT images acquired with an OCT needle probe, allowing tracking of individual alveoli during simulated cyclical lung inflation and deflation.

Ultrathin side-viewing needle probe for optical coherence tomography

We present the smallest reported side-viewing needle probe for optical coherence tomography (OCT). Design, fabrication, optical characterization, and initial application of a 30-gauge (outer diameter 0.31 mm) needle probe are demonstrated. Extreme miniaturization is achieved by using a simple all-fiber probe design incorporating an angle-polished and reflection-coated fiber-tip beam deflector. When inserted into biological tissue, aqueous interstitial fluids reduce the probe's inherent astigmatism ratio to 1.8, resulting in a working distance of 300 μm and a depth-of-field of 550 μm with beam diameters below 30 μm. The needle probe was interfaced with an 840 nm spectral-domain OCT system and the measured sensitivity was shown to be only 7 dB lower than that of a comparable galvo-scanning sample arm configuration. 3D OCT images of lamb lungs were acquired over a depth range of ~600 μm, showing individual alveoli and bronchioles.

Non-Invasive Microstructure and Morphology Investigation of the Mouse Lung: Qualitative Description and Quantitative Measurement

BackgroundEarly detection of lung cancer is known to improve the chances of successful treatment. However, lungs are soft tissues with complex three-dimensional configuration. Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents. It is difficult to obtain adequate information of lung lesions from conventional X-ray imaging.MethodsIn this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used. This powerful technique enabled high-resolution investigations of soft tissues without contrast agents. We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung.FindingsThe three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways. We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D). The precise view of individual alveolus was achieved. The morphological parameters, such as diameter and alveolar surface area were measured. These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar.ConclusionOur results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung. This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level.

Theoretical modeling of the interaction between alveoli during inflation and deflation in normal and diseased lungs

Alveolar recruitment is a central strategy in the ventilation of patients with acute lung injury and other lung diseases associated with alveolar collapse and atelectasis. However, biomechanical insights into the opening and collapse of individual alveoli are still limited. A better understanding of alveolar recruitment and the interaction between alveoli in intact and injured lungs is of crucial relevance for the evaluation of the potential efficacy of ventilation strategies. We simulated human alveolar biomechanics in normal and injured lungs. We used a basic simulation model for the biomechanical behavior of virtual single alveoli to compute parameterized pressure–volume curves. Based on these curves, we analyzed the interaction and stability in a system composed of two alveoli. We introduced different values for surface tension and tissue properties to simulate different forms of lung injury. The data obtained predict that alveoli with identical properties can coexist with both different volumes and with equal volumes depending on the pressure. Alveoli in injured lungs with increased surface tension will collapse at normal breathing pressures. However, recruitment maneuvers and positive endexpiratory pressure can stabilize those alveoli, but coexisting unaffected alveoli might be overdistended. In injured alveoli with reduced compliance collapse is less likely, alveoli are expected to remain open, but with a smaller volume. Expanding them to normal size would overdistend coexisting unaffected alveoli. The present simulation model yields novel insights into the interaction between alveoli and may thus increase our understanding of the prospects of recruitment maneuvers in different forms of lung injury.