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Lung tissue mechanics and parenchyma remodelling in respiratory diseases
Track 13. Respiratory Mechanics With no gravity, there is not flow interaction between the upper and lower half plug domains, however, when gravity is acting not parallel to the flow direction, fluid is found to flow from the upper precursor film, through the plug core, then to the lower trailing film. This interaction increases as Bo and plug speed increases. The lower (upper) trailing film thickness increases (decreases) with increasing Bo. The upper to lower film thickness ratio decreases with increasing Bo but increases with plug speed. The total mass left behind increases with Bo, plug speed and ~J,.The volume ratio, defined as the ratio of the liquid above to that below the center line of the channel is found to increase with LP but decrease with increasing Bo. The presence of surfactant causes both upper and lower film thickness increases, volume ratio increases while the wall shear stress decreases. This work is supported by NIH grant HL-41126, HL64373, NSF grant BES9820967, NASA grant NAG3-2196 and NAG3-2740.
13.3. Mechanics of the Lung Parenchyma 5967 Tu, 16:00-16:15 (P24) Lung tissue mechanics: from extracellular matrix to alveolar network behavior B. Suki, H. Parameswaran, A. Majumdar. Department ef Biomedical Engineering, Boston University, Boston, MA, USA The lung tissue is constantly under a preexisting tensile stress also called prestress which results from the distension of the lung by the transpulmonary pressure. The regional distribution of the prestress is determined by the hydrostatic pressure in the pleural space and the shape of the lung. Superimposed on this prestress are additional stresses due to breathing which change cyclically and irregularly. The prestress in the alveolar wall is transferred through the extracellular matrix (ECM) to the adhering cells with important consequences on cellular biophysics, biochemistry and phenotype which will also modulate connective tissue homeostasis itself. The interaction between the ECM and cellular biochemistry also has important implications for the biomechanical properties of the connective tissues. Recently, we have argued that collagen plays a major role in transmitting the transpulmonary pressure to lung cells in the alveolar septa through a hierarchical transmission of mechanical stimuli from the level of the whole lung down to single cells with various possible feedback loops controlling ECM remodeling and ultimately organ level mechanics. In this multiple loops, the alveolar wall network plays an important role since it must respond to any changes in local stiffness. We have developed several models of the parenchyma using a two-dimensional hexagonal spring network model. The model is able to account for many functional properties of the normal and the emphysematous lung such as the deterioration of lung function due to rupture of collagen in the alveolar septa. We also demonstrate how such a modeling approach can be used to pinpoint regions of high and low mechanical forces in histologic slide which in turn can be correlated with the expression of various ECM structural proteins and remodeling enzymes. 7934 Tu, 16:15-16:30 (P24) Lung tissue mechanics and parenchyma remodelling in respiratory diseases P.R.M. Rocco. Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Remodelling is defined as model to again or reconstruct differently. This is a critical aspect of wound repair in all organs, representing a dynamic process that associates matrix production and degradation in reaction to an inflammatory insult that leads to a normal reconstruction process (model again) or a pathologic one (model differently). Studies performed in our laboratory were undertaken to characterize lung parenchyma remodelling at different respiratory diseases as well as the dynamic mechanical properties of parenchyma tissue. The method used to determine lung tissue mechanics avoided the influence of kinetics of surface-active molecule absorptiondesorption to the surface film and of recruitment~Jerecruitment. Consequently a direct analysis of the role of fibre-fibre networking within the connective tissue matrix on tissue mechanical properties is ensured. Tissue mechanical properties of lung parenchyma were studied in experimental models of acute lung injury and chronic and severe asthma. Furthermore, the effects of different therapies employed in these models were also analysed. Tissue resistance, dynamic elastance, and hysteresivity were measured and these parameters were correlated with lung morphometric data and with collagen and elastic fibre content in the alveolar septa. A better understanding of both the mechanics and histology of lung parenchyma may be important for planning supportive and definitive therapies for these diseases. Supported by: PRONEX-FAPERJ, CNPq, FAPERJ.
13.3. Mechanics of the Lung Parenchyma
$267
4371 Tu, 16:30-16:45 (P24) Micromechanics of injured lungs R.D. Hubmayr. Mayo Clinic College of Medicine, Department of Physiology and Biomedical Engineering. Rochester, MN, USA Many controversies about mechanical ventilation associated injury mechanisms can be traced to uncertainties about the small scale stress and strain distributions in healthy and diseased lungs. In my presentation I will first review the physical determinants of regional lung volume and ventilation in healthy lungs and only then consider the effects of injury and edema on regional mechanics within this framework. I consider it important to detail certain principles in solid mechanics that are applicable to lung biology, not because the principles are new, but because they are fundamental for dealing with the topic at hand. I will provide experimental evidence that the mechanics of injured lungs are dominated by a small scale heterogeneity in interfacial tensions arising from alveolar edema and foam in small airways. Consequently, I will argue that the injured lung is not simply a heavy lung that is collapsed under its own weight. I will interpret disease related changes in whole respiratory system pressure volume curves and dependent densities of computer tomographic lung images in this context and conclude by addressing the implications of altered lung mechanics for Ventilator Induced Lung Injury, its prevention and its management. 5190 Tu, 16:45-17:00 (P24) Cell biomechanics of the alveolar epithelium D. Navajas. Unitat de Biofisica i Bioenginyeria. Facultat Medicina, Universitat Barcelona, Spain The alveolar epithelium forms a semipermeable barrier between the alveolar airspace and the lung interstitium. The integrity of the cell monolayer is governed by a dynamic force balance at the cell-cell and cell-matrix attachments between centripetal cell mechanical tension and tethering adhesive forces. Mechanical tension arises from both active contraction generated by the actomyosin machinery and passive viscoelastic recoil caused by cyclic stretching due to breathing or mechanical ventilation. A key feature of acute lung injury is alveolar flooding and infiltration of inflammatory cells into the alveolar compartment, which reflects structural failure of the alveolar barrier. A better understanding of the mechanisms that regulate the integrity of the alveolar barrier in injured lungs requires knowledge of the cell mechanical properties in response to stretch and inflammatory activation. Alveolar epithelial cells exhibit viscoelastic behavior with a complex elastic modulus increasing with frequency as a weak power-law ( G * - ~ x-l) and with a structural damping coefficient ~/-0.3. Stretch increases cell stiffness and reduces both ~l and frequency dependence. The inflammatory mediator thrombin enhances acto-myosin contraction associated with cell stiffening and a reduction in 'q and frequency dependence. This behavior conforms to soft glassy rheology, suggesting that cytoskeleton prestress modulates the elastic and frictional properties of alveolar epithelial cells. Stretch and thrombin cause minor cell detachment in confluent cell monolayers, indicating that the increased centripetal tension is compensated by the tethering adhesive forces. By contrast, stretching non confluent monolayers treated with thrombin results in substantial cell detachment, suggesting that inflammatory activation could exacerbate barrier dysfunction in injured lungs subjected to mechanical ventilation. 4390 Tu, 17:00-17:15 (P24) A four dimensional alveolar model of the lung H. Kitaoka. Graduate School of Medicine, Osaka University, Suita City, Japan Purpose: It is essential for respiratory physiology to understand the alveolar structure as a four dimensional (4D) object which exists in three dimensional (3D) space and changes its configuration along the time axis. However, little is known about the alveolar deformation, since there have been no imaging techniques for observing dynamic behavior of alveoli in 3D space. We have constructed a 4D alveolar model based on the known morphogenetic process of lung development and the known mechanical properties. Method: The algorithm for the 3D alveolar model consists of three morphogenetic processes of alveoli through which the alveolar wall receives homeomorphic deformation: the original smooth wall (inter-ductal wall) in the pseudo glandular stage is deformed like a bellow in the canalicular stages, and additional septa (intra-ductal wall) are grown at ridges of the bellow-like wall in the alveolar stage. We have modeled the mechanical property of the alveolar structure as a combination of springs and rigid plates connected by hinges. Springs correspond to elastic fibers at alveolar mouths, and hinges correspond to bellow-like arrangement of inter-ductal walls. The basic idea of the spring-hinge model is that the lung parenchyma changes its size by changing hinge angles of inter-ductal walls through the elasticity of springs. Result: Morphometric characteristics of the model were consistent with previous reports in literatures. The model explained how the alveolar number and the alveolar size would change at full ventilation cycle. Simulated microscopic
13.3. Mechanics of the Lung Parenchyma 5967 Tu, 16:00-16:15 (P24) Lung tissue mechanics: from extracellular matrix to alveolar network behavior B. Suki, H. Parameswaran, A. Majumdar. Department ef Biomedical Engineering, Boston University, Boston, MA, USA The lung tissue is constantly under a preexisting tensile stress also called prestress which results from the distension of the lung by the transpulmonary pressure. The regional distribution of the prestress is determined by the hydrostatic pressure in the pleural space and the shape of the lung. Superimposed on this prestress are additional stresses due to breathing which change cyclically and irregularly. The prestress in the alveolar wall is transferred through the extracellular matrix (ECM) to the adhering cells with important consequences on cellular biophysics, biochemistry and phenotype which will also modulate connective tissue homeostasis itself. The interaction between the ECM and cellular biochemistry also has important implications for the biomechanical properties of the connective tissues. Recently, we have argued that collagen plays a major role in transmitting the transpulmonary pressure to lung cells in the alveolar septa through a hierarchical transmission of mechanical stimuli from the level of the whole lung down to single cells with various possible feedback loops controlling ECM remodeling and ultimately organ level mechanics. In this multiple loops, the alveolar wall network plays an important role since it must respond to any changes in local stiffness. We have developed several models of the parenchyma using a two-dimensional hexagonal spring network model. The model is able to account for many functional properties of the normal and the emphysematous lung such as the deterioration of lung function due to rupture of collagen in the alveolar septa. We also demonstrate how such a modeling approach can be used to pinpoint regions of high and low mechanical forces in histologic slide which in turn can be correlated with the expression of various ECM structural proteins and remodeling enzymes. 7934 Tu, 16:15-16:30 (P24) Lung tissue mechanics and parenchyma remodelling in respiratory diseases P.R.M. Rocco. Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil Remodelling is defined as model to again or reconstruct differently. This is a critical aspect of wound repair in all organs, representing a dynamic process that associates matrix production and degradation in reaction to an inflammatory insult that leads to a normal reconstruction process (model again) or a pathologic one (model differently). Studies performed in our laboratory were undertaken to characterize lung parenchyma remodelling at different respiratory diseases as well as the dynamic mechanical properties of parenchyma tissue. The method used to determine lung tissue mechanics avoided the influence of kinetics of surface-active molecule absorptiondesorption to the surface film and of recruitment~Jerecruitment. Consequently a direct analysis of the role of fibre-fibre networking within the connective tissue matrix on tissue mechanical properties is ensured. Tissue mechanical properties of lung parenchyma were studied in experimental models of acute lung injury and chronic and severe asthma. Furthermore, the effects of different therapies employed in these models were also analysed. Tissue resistance, dynamic elastance, and hysteresivity were measured and these parameters were correlated with lung morphometric data and with collagen and elastic fibre content in the alveolar septa. A better understanding of both the mechanics and histology of lung parenchyma may be important for planning supportive and definitive therapies for these diseases. Supported by: PRONEX-FAPERJ, CNPq, FAPERJ.
13.3. Mechanics of the Lung Parenchyma
$267
4371 Tu, 16:30-16:45 (P24) Micromechanics of injured lungs R.D. Hubmayr. Mayo Clinic College of Medicine, Department of Physiology and Biomedical Engineering. Rochester, MN, USA Many controversies about mechanical ventilation associated injury mechanisms can be traced to uncertainties about the small scale stress and strain distributions in healthy and diseased lungs. In my presentation I will first review the physical determinants of regional lung volume and ventilation in healthy lungs and only then consider the effects of injury and edema on regional mechanics within this framework. I consider it important to detail certain principles in solid mechanics that are applicable to lung biology, not because the principles are new, but because they are fundamental for dealing with the topic at hand. I will provide experimental evidence that the mechanics of injured lungs are dominated by a small scale heterogeneity in interfacial tensions arising from alveolar edema and foam in small airways. Consequently, I will argue that the injured lung is not simply a heavy lung that is collapsed under its own weight. I will interpret disease related changes in whole respiratory system pressure volume curves and dependent densities of computer tomographic lung images in this context and conclude by addressing the implications of altered lung mechanics for Ventilator Induced Lung Injury, its prevention and its management. 5190 Tu, 16:45-17:00 (P24) Cell biomechanics of the alveolar epithelium D. Navajas. Unitat de Biofisica i Bioenginyeria. Facultat Medicina, Universitat Barcelona, Spain The alveolar epithelium forms a semipermeable barrier between the alveolar airspace and the lung interstitium. The integrity of the cell monolayer is governed by a dynamic force balance at the cell-cell and cell-matrix attachments between centripetal cell mechanical tension and tethering adhesive forces. Mechanical tension arises from both active contraction generated by the actomyosin machinery and passive viscoelastic recoil caused by cyclic stretching due to breathing or mechanical ventilation. A key feature of acute lung injury is alveolar flooding and infiltration of inflammatory cells into the alveolar compartment, which reflects structural failure of the alveolar barrier. A better understanding of the mechanisms that regulate the integrity of the alveolar barrier in injured lungs requires knowledge of the cell mechanical properties in response to stretch and inflammatory activation. Alveolar epithelial cells exhibit viscoelastic behavior with a complex elastic modulus increasing with frequency as a weak power-law ( G * - ~ x-l) and with a structural damping coefficient ~/-0.3. Stretch increases cell stiffness and reduces both ~l and frequency dependence. The inflammatory mediator thrombin enhances acto-myosin contraction associated with cell stiffening and a reduction in 'q and frequency dependence. This behavior conforms to soft glassy rheology, suggesting that cytoskeleton prestress modulates the elastic and frictional properties of alveolar epithelial cells. Stretch and thrombin cause minor cell detachment in confluent cell monolayers, indicating that the increased centripetal tension is compensated by the tethering adhesive forces. By contrast, stretching non confluent monolayers treated with thrombin results in substantial cell detachment, suggesting that inflammatory activation could exacerbate barrier dysfunction in injured lungs subjected to mechanical ventilation. 4390 Tu, 17:00-17:15 (P24) A four dimensional alveolar model of the lung H. Kitaoka. Graduate School of Medicine, Osaka University, Suita City, Japan Purpose: It is essential for respiratory physiology to understand the alveolar structure as a four dimensional (4D) object which exists in three dimensional (3D) space and changes its configuration along the time axis. However, little is known about the alveolar deformation, since there have been no imaging techniques for observing dynamic behavior of alveoli in 3D space. We have constructed a 4D alveolar model based on the known morphogenetic process of lung development and the known mechanical properties. Method: The algorithm for the 3D alveolar model consists of three morphogenetic processes of alveoli through which the alveolar wall receives homeomorphic deformation: the original smooth wall (inter-ductal wall) in the pseudo glandular stage is deformed like a bellow in the canalicular stages, and additional septa (intra-ductal wall) are grown at ridges of the bellow-like wall in the alveolar stage. We have modeled the mechanical property of the alveolar structure as a combination of springs and rigid plates connected by hinges. Springs correspond to elastic fibers at alveolar mouths, and hinges correspond to bellow-like arrangement of inter-ductal walls. The basic idea of the spring-hinge model is that the lung parenchyma changes its size by changing hinge angles of inter-ductal walls through the elasticity of springs. Result: Morphometric characteristics of the model were consistent with previous reports in literatures. The model explained how the alveolar number and the alveolar size would change at full ventilation cycle. Simulated microscopic