No evidence for mesothelial cell contact across the costal pleural space of sheep

Pleural space width was measured by four morphological approaches using either frozen hydrated or freeze-substituted blocks of chest wall and lung. Anesthetized sheep were held in the lateral (n = 2), sternal recumbent (n = 2), or vertical (head-up; n = 2) position for 30 min. The ribs and intercostal muscles were excised along a 20-cm vertical distance of the chest wall region, which was sprayed with liquid Freon 22, cooled with liquid nitrogen, to facilitate the fastest possible freezing of the visceral and parietal pleura. We measured pleural space width in frozen hydrated blocks by reflected-light and low-temperature scanning electron microscopy and in freeze-substituted, fixed, and embedded tissue blocks by light and transmission electron microscopy. We combined the data from the two groups of sheep held sternally recumbent and vertical because the results were comparable. The average arithmetic mean data for pleural space width determined by reflected-light analysis for samples near the top (18.5 microns) and bottom (20.3 microns) of the chest, separated by 15 cm of lung height, varied inversely with lung height (n = 4; P less than 0.009). The average harmonic mean data demonstrated a similar gravity-dependent gradient (17.3 and 18.8 microns, respectively; P less than 0.02). Therefore a slight vertical gradient of approximately -0.10 micron/cm of lung height was found for costal pleural space width. Pleural space width in the most dependent recesses, such as the costodiaphragmatic recess, reached 1-2 mm. We never found any contacts between the visceral and parietal pleura with either of the frozen hydrated preparations. No points of mesothelial cell contact were revealed in the light- and transmission electron microscopic views of the freeze-substituted tissue, despite an apparent narrower pleural space associated with the tissue-processing steps. We conclude that the pleural space has a slightly nonuniform width, contacts if they occur must be very infrequent, and pleural liquid clearance is probably facilitated by liquid accumulation in dependent regions where lymphatic pathways exist.     

Measurement of alveolar pressure in closed-chest dogs during flow interruption

We have developed a technique for installing alveolar capsules in dogs with intact chest wall, by exposing a region of parietal pleura between a pair of ribs and gluing the parietal and visceral pleura together around a small region of lung. This allows the direct measurement of alveolar pressure during spontaneous breathing. We measured alveolar pressure in normal dogs using this technique while suddenly interrupting flow at the trachea during passive expiration. Tracheal pressure exhibited a very rapid rise immediately on interruption that we showed to be composed of two distinct and roughly equal parts: one was the resistive pressure drop across the airways, and the other was a resistive pressure drop across tissues. By simultaneously measuring pleural pressure we showed that the tissues responsible were only in the chest wall and not in the lungs.     

Pleural liquid pressure in dogs measured using a rib capsule

We have developed a minimally invasive method for measuring the hydrostatic pressure in the pleural space liquid. A liquid-filled capsule is bonded into a rib and a small hole is cut in the parietal pleura to allow direct communication between the liquid in the capsule and the pleural space. The pressure can be measured continuously by a strain gauge transducer connected to the capsule. The rib capsule does not distort the pleural space or require removal of intercostal muscle. Pneumothoraces are easily detected when they occur inadvertently on puncturing the parietal pleura. We examined the effect of height on pleural pressure in 15 anesthetized spontaneously breathing dogs. The vertical gradients in pleural pressure were 0.53, 0.42, 0.46, and 0.23 cmH2O/cm height for the head-up, head-down, supine, and prone body positions, respectively. These vertical gradients were much less than the hydrostatic value (1 cmH2O/cm), indicating that the pleural liquid is not in hydrostatic equilibrium. In most body positions the magnitudes of pleural liquid pressure interpolated to midchest level were similar to the mean transpulmonary (surface) pressure determined postmortem. This suggests that pleural liquid pressure is closely related to the lung static recoil.     

Probing softness of the parietal pleural surface at the micron scale

The pleural surfaces of the chest wall and lung slide against each other, lubricated by pleural fluid. During sliding motion of soft tissues, shear induced hydrodynamic pressure deforms the surfaces, promoting uniformity of the fluid layer thickness, thereby reducing friction. To assess pleural deformability at length scales comparable to pleural fluid thickness, we measured the modulus of the parietal pleura of rat chest wall using atomic force microscopy (AFM) to indent the pleural surface with spheres (radius 2.5 and 5 μm). The pleura exhibited two distinct indentation responses depending on location, reflecting either homogeneous or significantly heterogeneous tissue properties. We found an elastic modulus of 0.38-0.95 kPa, lower than the values measured using flat-ended cylinders >100 μm radii (Gouldstone et al., 2003, Journal of Applied Physiology 95, 2345-2349). Interestingly, the pleura exhibited a three-fold higher modulus when probed using 2.5 vs. 5 μm spherical tips at the same normalized depth, confirming depth dependent inhomogeneous elastic properties. The observed softness of the pleura supports the hypothesis that unevenness of the pleural surface on this scale is smoothed by local hydrodynamic pressure.     

On the respiratory function of the ribs.

To assess the respiratory function of the ribs, we measured the changes in airway opening pressure (Pao) induced by stimulation of the parasternal and external intercostal muscles in anesthetized dogs, first before and then after the bony ribs were removed from both sides of the chest. Stimulating either set of muscles with the rib cage intact elicited a fall in Pao in all animals. After removal of the ribs, however, the fall in Pao produced by the parasternal intercostals was reduced by 60% and the fall produced by the external intercostals was eliminated. The normal outward curvature of the rib cage was also abolished in this condition, and when the curvature was restored by a small inflation, external intercostal stimulation consistently elicited a rise rather than a fall in Pao. These findings thus confirm that the ribs play a critical role in the act of breathing by converting intercostal muscle shortening into lung volume expansion. In addition, they carry the compression that is required to balance the pressure difference across the chest wall.     

Regional blood flow to canine parietal pleura and internal intercostal muscle

Transcapillary Starling forces in the parietal pleura and the underlying interstitium may potentially contribute to the exchange of fluid across this barrier. However, the extent of blood flow to the parietal pleura has not been measured. Thus, using standard microsphere techniques, we compared blood flow to the parietal pleura, including the subpleural interstitium, with blood flow to the adjacent internal intercostal muscle, as well as with flows to other serous tissues, including mediastinal pleura, pericardium, and parietal peritoneum, in anesthetized dogs that were either breathing spontaneously (n = 9) or ventilated to control arterial PCO2 (n = 5). Blood flow (ml.min-1.g-1) was measured after 20 min of equilibration in four successive body positions: right lateral decubitus, supine, left lateral decubitus, and prone. Overall, flow to parietal pleura was not different in spontaneous [1.07 +/- 0.14 (SE)] and mechanically ventilated animals (0.74 +/- 0.11). Flow to the internal intercostal muscle was significantly less than pleural blood flow, averaging 0.24 +/- 0.03 and 0.16 +/- 0.03 in the same groups, although again there was no effect of ventilation mode. Blood flow to other serous tissues in the thoracic cavity, specifically the mediastinal pleura (0.67 +/- 0.14) and pericardium (0.88 +/- 0.22), was similar to parietal pleural flow, whereas that to the parietal peritoneum was an order of magnitude lower (0.09 +/- 0.02, P less than 0.05). Changing body position had no effect on blood flow to any of the sampled tissues. Blood flow to the dorsal aspect of the chest wall muscle in spontaneously breathing animals tended to be greater than that to lateral or ventral portions of the chest wall.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pleural space thickness in situ by light microscopy in five mammalian species

The thickness of the pleural space was measured by a focusing method using a light microscope (X157, 2.5-micron depth of focus). In anesthetized animals, thin transparent parietal pleural windows were made by dissection of intercostal muscle. Multiple postmortem measurements were made of the combined thickness of the pleural space and the window by focusing in sequence on the lung surface and on 1- to 2-micron tantulum particles sprayed on the window. The window thickness was measured after creating a pneumothorax and retracting the lungs. In supine rabbits the pleural space measured at various heights on the costal surface was of uniform thickness (16 micron) except for a thicker region (62 micron) located within 3 mm of the most dependent part of the lung. The thicker region reverted to the uniform thickness after it was placed in a nondependent position by inverting the animal from the supine to prone position, indicating fluid drainage by gravity. In the prone position near midchest, pleural space thickness (t) averaged 6.9 micron in the mouse, 10.2 in the rat, 17.2 in the rabbit, 18.3 in the cat, and 23.6 in the dog. Animals of larger body mass (M, kg) had a wider pleural space: t = 13.1 X M0.20. There was no contact between the two pleurae, indicating that fluid lubrication facilitates sliding between the lung and chest wall. Based on the t vs. M relationship and estimates of the viscous flow of pleural liquid, pleural fluid exchange rate would be proportional to body mass and the work of sliding as a fraction of the work of breathing would be smaller in larger animals.     

Respiratory and circulatory effects of parietal pleural afferent stimulation in rabbits.

Respiratory symptoms accompanying pleural diseases combine dyspnea, tachypnea, rapid shallow breathing, and sometimes hypotension. There are no experimental data on the changes in respiratory and circulatory functions elicited by the activation of pleural afferents. After removal of all muscles covering the 5th to 10th intercostal spaces, we investigated in paralyzed, vagotomized rabbits the changes in phrenic discharge, transpulmonary pressure, and systemic arterial pressure in response to an outwardly directed force exerted on the parietal pleura or the local application of solutions containing lactic acid or inflammatory mediators. Mechanical stimulation of the pleura induced an immediate decrease in both integrated phrenic discharge and arterial blood pressure, the responses being positively correlated with the magnitude of force applied on the pleura. No accompanying changes in ventilatory timing, transpulmonary pressure, or heart rate were measured. Lactic acid solution also elicited an inhibition of phrenic activity and a fall in blood pressure. Section of the internal intercostal nerves supplying the stimulated intercostal spaces totally abolished the responses to mechanical stimulation or lactic acid. An inflammatory mixture elicited only modest respiratory and circulatory effects. We concluded that an acute mechanical distension of the parietal pleura as well as its chemical stimulation by lactic acid elicit a marked inhibition of phrenic motoneurons combined to a reduction of the sympathetic outflow to the circulatory system.     

Hydrodynamic thickening of lubricating fluid layer beneath sliding mesothelial tissues

The delicate mesothelial surfaces of the pleural space and other serosal cavities slide relative to each, lubricated by pleural fluid. In the absence of breathing motion, differences between lung and chest wall shape could eventually cause the lungs and chest wall to come into contact. Whether sliding motion keeps lungs and chest wall separated by a continuous liquid layer is not known. To explore the effects of hydrodynamic pressures generated by mesothelial sliding, we measured the thickness of the liquid layer beneath the peritoneal surface of a 3-cm disk of rat abdominal wall under a normal stress of 2 cm H2O sliding against a glass plate rotating at 0-1 rev/s. Thickness of the lubricating layer was determined microscopically from the appearance of fluorescent microspheres adherent to the tissue and glass. Usually, fluid thickness near the center of the tissue disk increased with the onset of glass rotation, increasing to 50-200 microm at higher rotation rates, suggesting hydrodynamic pumping. However, thickness changes often differed substantially among tissue samples and between clockwise and counter-clockwise rotation, and sometimes thickness decreased with rotation, suggesting that topographic features of the tissue are important in determining global hydrodynamic effects. We conclude that mesothelial sliding induces local hydrodynamic pressure gradients and global hydrodynamic pumping that typically increases the thickness of the lubricating fluid layer, moving fluid against the global pressure gradient. A similar phenomenon could maintain fluid continuity in the pleural space, reducing frictional force and shear stress during breathing.     

Effect of shape and size of lung and chest wall on stresses in the lung.

Conflicting results have been reported on the changes in the distribution of pleural pressures caused by alterations of chest shape. To understand better the effect of shape and size of lung and chest wall on the distribution of stresses, strains, and surface pressures, we analyzed a theoretical model using the technique of finite elements. The study was in two parts. First we investigated the effects of changing the chest wall shape during expansion, and second we studied lungs of a variety of inherent shapes and sizes. We found that, in general, the distributions of alveolar size, mechanical stresses, and surface pressures in the lungs were dominated by the weight of the lung and that changing the shape of the lung or chest wall had relatively little effect. Only at high states of expansion where the lung was very stiff did changing the shape of the chest wall cause substantial changes. Altering the inherent shape of the lung generally had little effect but the topographical differences in stresses and surface pressures were approximately proportional to lung height. The results are generally consistent with those found in dog by Hoppin et al. (J. Appl. Physiol. 27: 863-873, 1969).     

Permeability-surface area product and reflection coefficient of the parietal pleura in dogs.

The parameters describing the permeability of the parietal pleura to liquid and total plasma proteins were measured in five anesthetized adult dogs. Small areas of parietal pleura (approximately 1 cm2) and the underlying endothoracic fascia were exposed through resection of the skin and the intercostal muscles. The portion of the thorax containing the pleural windows was removed from the chest and fixed over a bath of whole autologous plasma, the inner parietal pleural surface facing the bath. Small hemispheric Perspex capsules (surface area 0.28 cm2) connected to a pressure manometer were glued to the pleural windows; a subatmospheric pressure was set into the capsule chamber to create step hydraulic transpleural pressure gradients (delta P) ranging from 5 to 60 cmH2O. Transpleural liquid flows (Jv) and protein concentration of the capsular filtrate (Cfilt) and of the plasma bath were measured at each delta P. The transpleural protein flux (Js) at each delta P was calculated by multiplying Jv by the corresponding Cfilt. The hydraulic conductivity (Lp) of the parietal pleura was obtained from the slope of the Jv vs. delta P linear regression. The average Lp from 14 capsules was 9.06 +/- 4.06 (SD) microliters.h-1.cmH2O-1.cm-2. The mathematical treatment of the Js vs. Jv relationship allowed calculation of the unique Peclet number at the maximal diffusional protein flux and a corresponding osmotic permeability coefficient for plasma protein of 1 x 10(-5) +/- 0.97 x 10(-5) cm/s. The reflection coefficient calculated from the slope of the linear phase of the Js vs. Jv relationship was 0.11 +/- 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional variations in lung expansion in rabbits: prone vs. supine positions

We studied the vertical gradient in lung expansion in rabbits in the prone and supine body positions. Postmortem, we used videomicroscopy to measure the size of surface alveoli through transparent parietal pleural windows at dependent and nondependent sites separated in height by 2-3 cm at functional residual capacity (FRC). We compared the alveolar size measured in situ with that measured in the isolated lungs at different deflationary transpulmonary pressures to obtain transpulmonary pressure (pleural surface pressure) in situ. The vertical gradient in transpulmonary pressure averaged 0.48 +/- 0.16 (SD) cmH2O/cm height (n = 10) in the supine position and 0.022 +/- 0.014 (SD) cmH2O/cm (n = 5) in the prone position. In mechanically ventilated rabbits, we used the rib capsule technique to measure pleural liquid pressure at different heights of the chest in prone and supine positions. At FRC, the vertical gradient in pleural liquid pressure averaged 0.63 cmH2O/cm in the supine position and 0.091 cmH2O/cm in the prone position. The vertical gradients in pleural liquid pressure were all less than the hydrostatic value (1 cmH2O/cm), which indicates that pleural liquid is not generally in hydrostatic equilibrium. Both pleural surface pressure and pleural liquid pressure measurements show a greater vertical gradient in the supine than in the prone position. This suggests a close relationship between pleural surface pressure and pleural liquid pressure. Previous results in the dog and pony showed relatively high vertical gradients in the supine position and relatively small gradients in the prone position. This behavior is similar to the present results in rabbits. Thus the vertical gradient is independent of animal size and might be related to chest shape and weight of heart and abdominal contents.     

Hydraulic conductivity of canine parietal pleura in vivo

The hydraulic conductivity (Lp) of the parietal pleura was measured in vivo in spontaneously breathing anesthetized dogs in either the supine (n = 8) or the prone (n = 7) position and in an excised portion of the chest wall in which the pleura and its adjacent tissue were intact (n = 3). A capsule was glued to the exposed parietal pleura after the intercostal muscles were removed. The capsule was filled with either autologous plasma or isotonic saline. Transpleural fluid flow (V) was measured at several transpleural hydrostatic pressures (delta P) from the rate of meniscus movement within a graduated pipette connected to the capsule. Delta P was defined as the measured difference between capsule and pleural liquid pressures. The Lp of the parietal pleura was calculated from the slope of the line relating V to delta P by use of linear regression analysis. Lp in vivo averaged 1.36 X 10(-3) +/- 0.45 X 10(-3) (SD) ml.h-1.cmH2O-1.cm-2, regardless of whether the capsule was filled with plasma or saline and irrespective of body position. This value was not significantly different from that measured in the excised chest wall preparation (1.43 X 10(-3) +/- 1.1 X 10(-3) ml.h-1.cmH2O-1.cm-2). The parietal pleura offers little resistance to transpleural protein movement, because there was no observed difference between plasma and saline. We conclude that because the Lp for intact parietal pleura and extrapleural interstitium is approximately 100 times smaller than that previously measured in isolated stripped pleural preparations, removal of parietal pleural results in a damaged preparation.     

The rib cage in normal and emphysematous subjects: a roentgenographic approach

The configuration and motion of the bony rib cage were studied from lateral chest roentgenograms in 10 young normal subjects (YN), 12 elderly normal subjects, and 12 hyperinflated emphysematous patients [chronic obstructive pulmonary disease subjects (COPD), mean total lung capacity (TLC) 133% of predicted]. The acute angles formed by the fourth through seventh ribs with an axial reference plane were measured at residual volume, functional residual capacity, and TLC in both supine and standing positions and correlated with corresponding lung volumes. both rib angles (RA) and changes in RA with lung volume were greatest with the fourth rib and decreased progressively going down (caudad) the chest. At TLC the RA of upper ribs was significantly less in EN and significantly greater in COPD than in YN. RA's were greater supine than standing. When RA information was used together with autopsy data on the angles formed by intercostal muscles with adjacent ribs, intercostal muscle lengths in hyperinflation could be calculated. Computed intercostal muscle length data suggested that hyperinflation should not be associated with degrees of intercostal muscle shortening or overstretching, that would interfere seriously with tension generation.     

Mechanics of the parasternal intercostals during occluded breaths in dogs

The electrical activity and the respiratory changes in length of the third parasternal intercostal muscle were measured during single-breath airway occlusion in 12 anesthetized, spontaneously breathing dogs in the supine posture. During occluded breaths in the intact animal, the parasternal intercostal was electrically active and shortened while pleural pressure fell. In contrast, after section of the third intercostal nerve at the chondrocostal junction and abolition of parasternal electrical activity, the muscle always lengthened. This inspiratory muscle lengthening must be related to the fall in pleural pressure; it was, however, approximately 50% less than the amount of muscle lengthening produced, for the same fall in pleural pressure, by isolated stimulation of the phrenic nerves. These results indicate that 1) the parasternal inspiratory shortening that occurs during occluded breaths in the dog results primarily from the muscle inspiratory contraction per se, and 2) other muscles of the rib cage, however, contribute to this parasternal shortening by acting on the ribs or the sternum. The present studies also demonstrate the important fact that the parasternal inspiratory contraction in the dog is really agonistic in nature.     

Enzyme release and morphological changes in leukocytes induced by mechanical trauma

Polymorphonuclear (PMN) leukocytes exposed to mechanical trauma in vitro will release enzymes both from azurophilic and specific granules at shear stress levels of between 75 and 150 dyn/cm2 for 10 min. In addition, at these shear stresses the leukocyte count in whole blood decreased only slightly and the number of ruptured leukocytes on Wright-stained blood films increased significantly. At higher shear stresses, enzyme release and leukocyte damage increased monotonically. Transmission electron microscopy evaluation of sheared PMNs revealed that remaining intact cells had minor morphological changes at stresses of 150 dyn/cm2. They were characterized by clublike cytoplasmic potrusions, spherical shape, and a circumferential distribution of cytoplasmic granules. At higher shear stresses (600 dyn/cm2) cell destruction was marked. Intact PMNs contained fewer cytoplasmic granules, a large number of vacuoles, and condensed nuclear chromatin. These studies show that PMN morphology and function are at least as sensitive to mechanical trauma as similar platelet alterations seen in other studies.     

Role of pleural pressure in the coupling between the intercostal muscles and the ribs.

The inspiratory intercostal muscles elevate the ribs and thereby elicit a fall in pleural pressure (DeltaPpl) when they contract. In the present study, we initially tested the hypothesis that this DeltaPpl does, in turn, oppose the rib elevation. The cranial rib displacement (Xr) produced by selective activation of the parasternal intercostal muscle in the fourth interspace was measured in dogs, first with the rib cage intact and then after DeltaPpl was eliminated by bilateral pneumothorax. For a given parasternal contraction, Xr was greater after pneumothorax; the increase in Xr per unit decrease in DeltaPpl was 0.98+/-0.11 mm/cmH2O. Because this relation was similar to that obtained during isolated diaphragmatic contraction, we subsequently tested the hypothesis that the increase in Xr observed during breathing after diaphragmatic paralysis was, in part, the result of the decrease in DeltaPpl, and the contribution of the difference in DeltaPpl to the difference in Xr was determined by using the relation between Xr and DeltaPpl during passive inflation. With diaphragmatic paralysis, Xr during inspiration increased approximately threefold, and 47+/-8% of this increase was accounted for by the decrease in DeltaPpl. These observations indicate that 1) DeltaPpl is a primary determinant of rib motion during intercostal muscle contraction and 2) the decrease in DeltaPpl and the increase in intercostal muscle activity contribute equally to the increase in inspiratory cranial displacement of the ribs after diaphragm paralysis.     

Elastic moduli of lungs during postnatal development in the piglet

Several manifestations of lung disease during infancy suggest that mechanical interdependence can be relatively high in newborn lungs. To test this possibility, we measured elastic moduli and pleural membrane tension in lungs excised from piglets ranging in age from less than 12 h to 85 days. Near maximum inflation, newborn lungs (less than 12 h, n = 6) had no detectable pleural membrane tension, although 3- to 5-day-old lungs (n = 6) had tension greater than 5,000 dyn/cm. In contrast, parenchymal recoil was greater in the newborn lungs [19.3 +/- 3.0 (SD) vs. 14.3 +/- 2.4 cmH2O at 90% of maximum inflation volume, P less than 0.01]. Shear moduli were higher (13.5 +/- 4.6 vs. 9.2 +/- 1.5 cmH2O at 15 cmH2O transpulmonary pressure, P less than 0.05) and Poisson ratios were lower in the newborn lungs as compared with the 3- to 5-day-old lungs. Postnatal lung growth between 3 and 85 days was characterized by 1) a constant shear modulus (0.6 times transpulmonary pressure); 2) decrease in the bulk modulus (from 6.8 to 5.1 times transpulmonary pressure, P less than 0.005); and 3) evidence of gas trapping at progressively higher transpulmonary pressures. Therefore, growth of parenchyma in the piglet lung is associated with reduced stiffness to volume change but with no effect on overall stiffness to shape change. Nevertheless, a relatively great stiffness to shape change occurs transiently in newborn piglet lungs.     

Experimental technique of measuring dynamic fluid shear stress on the aortic surface of the aortic valve leaflet

Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact cause and mechanism of the progression of AV calcification is unknown, although mechanical forces have been known to play a role. It is thus important to characterize the mechanical environment of the AV. In the current study, we establish a methodology of measuring shear stresses experienced by the aortic surface of the AV leaflets using an in vitro valve model and adapting the laser Doppler velocimetry (LDV) technique. The valve model was constructed from a fresh porcine aortic valve, which was trimmed and sutured onto a plastic stented ring, and inserted into an idealized three-lobed sinus acrylic chamber. Valve leaflet location was measured by obtaining the location of highest back-scattered LDV laser light intensity. The technique of performing LDV measurements near to biological surfaces as well as the leaflet locating technique was first validated in two phantom flow systems: (1) steady flow within a straight tube with AV leaflet adhered to the wall, and (2) steady flow within the actual valve model. Dynamic shear stresses were then obtained by applying the techniques on the valve model in a physiologic pulsatile flow loop. Results show that aortic surface shear stresses are low during early systole (<5 dyn/cm2) but elevated to its peak during mid to late systole at about 18-20 dyn/cm2. Low magnitude shear stress (<5 dyn/cm2) was observed during early diastole and dissipated to zero over the diastolic duration. Systolic shear stress was observed to elevate only with the formation of sinus vortex flow. The presented technique can also be used on other in vitro valve models such as congenitally geometrically malformed valves, or to investigate effects of hemodynamics on valve shear stress. Shear stress data can be used for further experiments investigating effects of fluid shear stress on valve biology, for conditioning tissue engineered AV, and to validate numerical simulations.     

Magnetic resonance assessment of parenchymal elasticity in normal and edematous, ventilator-injured lung

Magnetic resonance elastography (MRE) is a MR imaging method capable of spatially resolving the intrinsic mechanical properties of normal lung parenchyma. We tested the hypothesis that the mechanical properties of edematous lung exhibit local properties similar to those of a fluid-filled lung at transpulmonary pressures (P(tp)) up to 25 cm H(2)O. Pulmonary edema was induced in anesthetized female adult Sprague-Dawley rats by mechanical ventilation to a pressure of 40 cm H(2)O for ～30 min. Prior to imaging the wet weight of each ex vivo lung set was measured. MRE, high-resolution T(1)-weighted spin echo and T(2)* gradient echo data were acquired at each P(tp) for both normal and injured ex vivo lungs. At P(tp)s of 6 cm H(2)O and greater, the shear stiffness of normal lungs was greater than injured lungs (P ≤ 0.0003). For P(tp)s up to 12 cm H(2)O, shear stiffness was equal to 1.00, 1.07, 1.16, and 1.26 kPa for the injured and 1.31, 1.89, 2.41, and 2.93 kPa for normal lungs at 3, 6, 9, and 12 cm H(2)O, respectively. For injured lungs MRE magnitude signal and shear stiffness within regions of differing degrees of alveolar flooding were calculated as a function of P(tp). Differences in shear stiffness were statistically significant between groups (P < 0.001) with regions of lower magnitude signal being stiffer than those of higher signal. These data demonstrate that when the alveolar space filling material is fluid, MRE-derived parenchymal shear stiffness of the lung decreases, and the lung becomes inherently softer compared with normal lung.