Alveolar expansion imaged by optical sectioning microscopy

Perlman, Carrie E.; Bhattacharya, Jahar

doi:10.1152/japplphysiol.00160.2007

Cited by 117 publications

(137 citation statements)

References 38 publications

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“…Using the line-measuring cursor of the image analysis software, we traced the alveolar margin and determined the alveolar perimeter length (3). From the number of pixels enclosed by the traced line, we determined the alveolar cross-sectional area.…”

Section: Resultsmentioning

confidence: 99%

“…We anesthetized adult, male Sprague-Dawley rats (n 5 17, 300-600 g) with 5% isoflurane, followed by 80 mg/kg ketamine and 8 mg/kg xylazine. Then we produced the isolated, perfused lung preparation, as described previously (3). Perfusion pressures were 10 and 3 cm H 2 O in the pulmonary artery and left atrium, respectively.…”

Section: Animalsmentioning

confidence: 99%

“…We imaged lungs by confocal microscopy, using morphologic landmarks to identify the same alveolus at different lung volumes (3). To view the margin of air-filled alveoli, we loaded the alveolar epithelium with calcein red-orange AM (3).…”

Section: Experimental Protocolmentioning

confidence: 99%

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Micromechanics of Alveolar Edema

Perlman

Lederer²,

Bhattacharya³

2011

Am J Respir Cell Mol Biol

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104

106

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The decrease of lung compliance in pulmonary edema underlies ventilator-induced lung injury. However, the cause of the decrease in compliance is unknown. We tested the hypothesis that in pulmonary edema, the mechanical effects of liquid-filled alveoli increase tissue stress in adjacent air-filled alveoli. By micropuncture of isolated, perfused rat lungs, we established a single-alveolus model of pulmonary edema that we imaged using confocal microscopy. In this model, we viewed a liquid-filled alveolus together with its airfilled neighbor at different transpulmonary pressures, both before and after liquid-filling. Instilling liquid in an alveolus caused alveolar shrinkage. As a result, the interalveolar septum was stretched, causing the neighboring air-filled alveolus to bulge. Thus, the airfilled alveolus was overexpanded by virtue of its adjacency to a liquid-filled alveolus. Confocal microscopy at different depths of the liquid-filled alveolus revealed a meniscus. Lung inflation to neartotal lung capacity (TLC) demonstrated decreased compliance of the air-filled but not liquid-filled alveolus. However, at near TLC, the airfilled alveolus was larger than it was in the pre-edematous control tissue. In pulmonary edema, liquid-filled alveoli induce mechanical stress on air-filled alveoli, reducing the compliance of air-filled alveoli, and hence overall lung compliance. Because of increased mechanical stress, air-filled alveoli may be susceptible to overdistension injury during mechanical ventilation of the edematous lung.Keywords: alveolar edema; compliance; micromechanics; optical sectioning microscopy; fluorescence Pulmonary edema occurs in a stepwise manner such that in its initial stages, liquid-filled and air-filled alveoli lie juxtaposed to one another. This liquid-filling pattern is thought to result from the all-or-none mechanism (1), according to which the curved air-liquid interface in the alveolus establishes a transinterfacial force balance, governed according to the equation of Laplace. In this equation (P alv 2 P liq ) 5 2T/R, where P alv and P liq are pressures in the alveolar air and liquid, respectively, T is the airliquid interfacial surface tension, and R is the interfacial radius. The alveolar entry of edema liquid at constant P alv is thought to increase T, thereby reducing P liq and further promoting liquid entry from the interstitium. This process continues until the interfacial curvature, and thus the pressure difference across the interface, is abolished. Importantly, these force considerations may be sufficiently localized that a single alveolus fills with fluid, while its immediate neighbor remains air-filled.Although the all-or-none mechanism provides an explanation of how single alveoli become liquid-filled during the initiating phase of pulmonary edema, there is little understanding of how the juxtaposition of air-filled and liquid-filled alveoli affects lung mechanics. The critical questions involve whether meniscus formation occurs in the liquid-filled alveolus (1, 2), and whether a...

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Section: Resultsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

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Micromechanics of Alveolar Edema

Perlman

Lederer²,

Bhattacharya³

2011

Am J Respir Cell Mol Biol

Self Cite

104

106

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“…The alveoli expand nonuniformly and increase in size by a mean of 14% during respiration (Perlman & Bhattacharya, 2007). With nonuniform expansion weak points can be formed during respiration.…”

Section: Discussionmentioning

confidence: 99%

The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results

Bernstein¹,

Rogers²,

Sepulveda³

et al. 2010

Inhalation Toxicology

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“…However, ATII cells may experience considerably less deformation than alveolar type I cells in vivo (29). This should especially be considered when studying the effects of high stretch amplitudes on ATII cells in culture with the situation in vivo.…”

Section: Discussionmentioning

confidence: 99%

Mechanical strain of alveolar type II cells in culture: changes in the transcellular cytokeratin network and adaptations

Felder¹,

Siebenbrunner²,

Busch³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical forces exert multiple effects in cells, ranging from altered protein expression patterns to cell damage and death. Despite undisputable biological importance, little is known about structural changes in cells subjected to strain ex vivo. Here, we undertake the first transmission electron microscopy investigation combined with fluorescence imaging on pulmonary alveolar type II cells that are subjected to equibiaxial strain. When cells are investigated immediately after stretch, we demonstrate that curved cytokeratin (CK) fibers are straightened out at 10% increase in cell surface area (CSA) and that this is accompanied by a widened extracellular gap of desmosomesthe insertion points of CK fibers. Surprisingly, a CSA increase by 20% led to higher fiber curvatures of CK fibers and a concurrent return of the desmosomal gap to normal values. Since 20% CSA increase also induced a significant phosphorylation of CK8-ser431, we suggest CK phosphorylation might lower the tensile force of the transcellular CK network, which could explain the morphological observations. Stretch durations of 5 min caused membrane injury in up to 24% of the cells stretched by 30%, but the CK network remained surprisingly intact even in dead cells. We conclude that CK and desmosomes constitute a strong transcellular scaffold that survives cell death and hypothesize that phosphorylation of CK fibers is a mechano-induced adaptive mechanism to maintain epithelial overall integrity. mechanical stress; cytoskeleton; desmosome; injury MANY CELL TYPES are subjected to deformation or other mechanical forces. An increasing number of studies has addressed cellular and molecular mechanisms that lead to coordinated responses of cells to such stimuli (for review, see Refs. 1, 23). Besides physiological responses occurring within a tolerable range of mechanical stress, a certain level of deformation inevitably threatens the structural integrity of the cell and leads to cell death. Little is known about structural cell changes in this life-threatening state, and even less is known about possible defense mechanisms a cell might employ to resist potentially fatal amplitudes of tensile stress. The goal of this study was to gather basic information regarding these questions on a cellular level by application of controlled strain to cells in culture, allowing direct comparison of stretched cells with unstretched controls.We used primary cultures of alveolar type II (ATII) cells, the most abundant cell type in the lung, because in vivo this cell type is exposed to life-long mechanical strain during breathing. Although different lung volumes (as % of total lung capacity) were suggested (2, 36, and for a review, see Ref. 5) to induce single cell stretch on a cellular level, it has been shown that within a certain range, these cells respond to mechanical distension with release of surfactant into the alveolus in vivo (25, 27) as well as in vitro (13, 43). Repetitive stretch induces a variety of cellular responses associated with gene regulation and protein...

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Alveolar expansion imaged by optical sectioning microscopy

Cited by 117 publications

References 38 publications

Micromechanics of Alveolar Edema

Micromechanics of Alveolar Edema

The pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite asbestos following short-term inhalation exposure: interim results

Mechanical strain of alveolar type II cells in culture: changes in the transcellular cytokeratin network and adaptations

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