Effect of lung inflation on regional lung expansion in supine and prone rabbits

At functional residual capacity, lung expansion is more uniform in the prone position than in the supine position. We examined the effect of positive airway pressure (Paw) on this position-dependent difference in lung expansion. In supine and prone rabbits postmortem, we measured alveolar size through dependent and nondependent pleural windows via videomicroscopy at Paw of 0 (functional residual capacity), 7, and 15 cmH2O. After the chest was opened, alveolar size was measured in the isolated lung at several transpulmonary pressures (Ptp) on lung deflation. Alveolar mean linear intercept (Lm) was measured from the video images taken in situ. This was compared with those measured in the isolated lung to determine Ptp in situ. In the supine position, the vertical Ptp gradient increased from 0.52 cmH2O/cm at 0 cmH2O Paw to 0.90 cmH2O/cm at 15 cmH2O Paw, while the vertical gradient in Lm decreased from 2.17 to 0.80 microns/cm. In the prone position, the vertical Ptp gradient increased from 0.06 cmH2O/cm at 0 cmH2O Paw to 0.35 cmH2O/cm at 15 cmH2O Paw, but there was no change in the vertical Lm gradient. In anesthetized paralyzed rabbits in supine and prone positions, we measured pleural liquid pressure directly at 0, 7, and 15 cmH2O Paw with dependent and nondependent rib capsules. Vertical Ptp gradients measured with rib capsules were similar to those estimated from the alveolar size measurements. Lung inflation during mechanical ventilation may reduce the vertical nonuniformities in lung expansion observed in the supine position, thereby improving gas exchange and the distribution of ventilation.     

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.     

Pleural pressure as a function of body position in rabbits

Pleural pressure was measured at end expiration in spontaneously breathing anesthetized rabbits. A liquid-filled capsule was implanted into a rib to measure pleural liquid pressure with minimal distortion of the pleural space. Capsule position relative to lung height was measured from thoracic radiographs. Measurements were made when the rabbits were in the prone, supine, right lateral, and left lateral positions. Average lung heights in the prone and supine positions were 4.21 +/- 0.58 and 4.42 +/- 0.51 (SD) cm, respectively (n = 7). Pleural pressure was -2.60 +/- 1.87 (SD) cmH2O at 50.2 +/- 7.75% lung height in the prone position and -3.10 +/- 1.22 cmH2O at 51.4 +/- 6.75% lung height in the supine position. There was no difference between the values recorded in the prone and supine positions. Placement of the capsule into the right or left chest had no effect on the magnitude of the pleural pressure recorded in rabbits in right and left lateral recumbency (n = 12). Measurements over the nondependent lung were repeatable when rabbits were turned between the right and left lateral positions. Lung height in laterally recumbent rabbits averaged 4.55 +/- 0.52 (SD) cm.     

Liquid thickness vs. vertical pressure gradient in a model of the pleural space

In recent studies using relatively noninvasive techniques, the vertical gradient in pleural liquid pressure was 0.2-0.5 cmH2O/cm ht, depending on body position, and pleural liquid pressure closely approximated lung recoil (J. Appl. Physiol. 59: 597-602, 1985). We built a model to discover why the vertical gradient in pleural pressure is less than hydrostatic (1 cmH2O/cm). A long rubber balloon of cylindrical shape was inflated in a plastic cylinder. The "pleural" space between the balloon and cylinder was filled with blue-dyed water. With the cylinder vertical, we measured pleural pressure by a transducer through side taps at 2-cm intervals up the cylinder. The pressure was measured with different amounts of water in the pleural space. With a clear separation between the balloon and the container, the vertical gradient in pleural liquid pressure was hydrostatic. As water was withdrawn from the pleural space, the balloon approached the wall of the container. Over an 8-cm-long midregion of the model where the balloon diameter matched the cylinder diameter, the vertical gradient was not hydrostatic and was virtually absent. In this region, the pleural liquid pressure was uniform and equal to the recoil of the balloon. In this section we could not see any pleural space. By scintillation imaging using 99mTc-diethylenetriamine pentaacetic acid in the water, we estimated the thickness of this flat "costal" pleural space to be approximately 20 microns. Radioactive tracer injected at the top of the pleural space appeared by 24 h at the bottom, which indicated a slow drainage of liquid by gravity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Size-related differences in parietal extrapleural and pleural liquid pressure distribution

The hydraulic pressure in the extrapleural parietal interstitium (Pepl) and in the pleural space over the costal side (Pliq) was measured in anesthetized spontaneously breathing supine adult mammals of increasing size (rats, dogs, and sheep) using saline-filled catheters and cannulas, respectively. From the Pliq and Pepl vs. lung height regressions it appears that in all species Pliq was significantly more subatmospheric than Pepl simultaneously measured at the same lung height. The vertical pleural liquid pressure gradient increased with size, amounting to -1, -0.69, and -0.44 cmH2O/cm in rats, dogs, and sheep, respectively. The vertical extrapleural liquid pressure gradient also increased with size, being -0.6, -0.52, and -0.33 cmH2O/cm in rats, dogs, and sheep, respectively. With increasing body size, the transpleural hydraulic pressure gradient (Ptp = Pepl - Pliq) at the level of the right atrium increased from 1.45 to 5.6 cmH2O going from rats to sheep. In all species Ptp increased, with lung height being greatest in the less dependent part of the pleural space.     

Volume-related and volume-independent effects of posture on esophageal and transpulmonary pressures in healthy subjects.

Ventilator management decisions in acute lung injury could be better informed with knowledge of the patient's transpulmonary pressure, which can be estimated using measurements of esophageal pressure. Esophageal manometry is seldom used for this, however, in part because of a presumed postural artifact in the supine position. Here, we characterize the magnitude and variability of postural effects on esophageal pressure in healthy subjects to better assess its significance in patients with acute lung injury. We measured the posture-related changes in relaxation volume and total lung capacity in 10 healthy subjects in four postures: upright, supine, prone, and left lateral decubitus. Then, in the same subjects, we measured static pressure-volume characteristics of the lung over a wide range of lung volumes in each posture by using an esophageal balloon catheter. Transpulmonary pressure during relaxation (PLrel) averaged 3.7 (SD 2.0) cmH2O upright and -3.3 (SD 3.2) cmH2O supine. Approximately 58% of the decrease in PLrel between the upright and supine postures was due to a corresponding decrease in relaxation volume. The remaining 2.9-cmH2O difference is consistent with reported values of a presumed postural artifact. Relaxation volumes and pressures in prone and lateral postures were intermediate. To correct estimated transpulmonary pressure for the effect of lying supine, we suggest adding 3 cmH2O (95% confidence interval: -1 to +7 cmH2O). We conclude that postural differences in estimated transpulmonary pressure at a given lung volume are small compared with the substantial range of PLrel in patients with acute lung injury.     

Influence of the heart on the vertical gradient of transpulmonary pressure in dogs

Estimations were made of the vertical gradient of transpulmonary pressure (VGTP) from measurements of esophageal pressure in nine head-up dogs at functional residual capacity (FRC) when alive, when dead, and after total bilateral pneumothorax. The VGTP of 0.4 cmH2O/cm height in the alive state was abolished by pneumothorax, and roentgenograms showed that the heart moved in a caudal-dorsal direction. There was a small but significant increase in the VGTP on going from FRC to near total lung capacity (TLC) in alive head-up dogs. In eight dead head-up dogs heart weight was increased by replacing various amounts of heart blood with Hg. The VGTP was significantly increased from 0.28 to 0.51 cmH2O/cm height. The fractional increase in the VGTP was similar to the fractional increase in heart weight. In five dogs extrapolation to zero heart weight gave an average VGTP of 0.14 cmH2O/cm height. We conclude that the lungs help support the heart in the head-up dog and that the VGTP is in part determined by the pressure distribution required for this support.     

Deformation of the dog lung in the chest wall

Data on the shape of the chest wall at total lung capacity (TLC) and functional residual capacity (FRC) were used as boundary conditions in an analysis of the deformation of the dog lung. The lung was modeled as an elastic body, and the deformation of the lung from TLC to FRC caused by the change in chest wall shape and gravity were calculated. Parenchymal distortions, distributions of regional volume at FRC as a fraction of the volume at TLC, and distributions of surface pressure at FRC are reported. In the prone dog there are minor variations in fractional volume along the cephalocaudal axis. In transverse planes opposing deformations are caused by the change of shape of the transverse section and the gravitational force on the lung, and the resultant fractional volume and pleural pressure distributions are nearly uniform. In the supine dog, there is a small cephalocaudal gradient in fractional volume, with lower fractional volume caudally. In transverse sections the heart and abdomen extend farther dorsally at FRC, squeezing the lung beneath them. The gradients in fractional volume and pleural pressure caused by shape changes are in the same direction as the gradients caused by the direct gravitational force on the lung, and these two factors contribute about equally to the large resultant vertical gradients in fractional volume and pleural pressure. In the prone position the heart and upper abdomen rest on the rib cage. In the supine posture much of their weight is carried by the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of body position on regional diaphragm function in dogs

The in situ lengths of muscle bundles of the crural and three regions of the costal diaphragm between origin and insertion were determined with a video roentgenographic technique in dogs. At total lung capacity (TLC) in both the prone and supine positions, the length of the diaphragm is not significantly different from the unstressed excised length, suggesting that the diaphragm is not under tension at TLC and that there is a hydrostatic gradient of pleural pressure on the diaphragmatic surface. Except for the ventral region of the costal diaphragm, which does not change length at lung volumes greater than 70% TLC, all other regions are stretched during passive deflations from TLC. Therefore below TLC the diaphragm is under passive tension and supports a transdiaphragmatic pressure (Pdi). The length of the diaphragm relative to its unstressed length is not uniform at functional residual capacity (FRC) and does not follow a strict vertical gradient that reverses when the animal is changed from the supine to the prone position. By inference, the length of muscle bundles is determined by factors other than the vertical gradient of Pdi. During mechanical ventilation, regional shortening is identical to the passive deflation length-volume relationship near FRC. Prone and supine FRC is the same, but the diaphragm is slightly shorter in the prone position. In both positions, during spontaneous ventilation there are no consistent differences in regional fractional shortening, despite regional differences in initial length relative to unstressed length.     

Simulation of the vertical gradient of transpulmonary pressure by stable foams

We describe a simulation of the vertical gradient of transpulmonary pressure (VGTP) using a stable foam, which is suitable for use in studies of the effect of the VGTP on excised lungs. We generated foams that produced linear hydrostatic pressure gradients (HPGs) from 0.18 to 0.44 cmH2O/cm depth, which were stable over time and were reproducible. The HPG was similar under static and dynamic conditions. The foam did not affect lung elastic properties or cause histological changes. We conclude that these stable foams provide a practical, inexpensive simulation of the VGTP and should be useful in studying the effects of the VGTP on regional lung behavior.     

Parenchymal stress affects interstitial and pleural pressures in in situ lung.

After resecting the intercostal muscles and thinning the endothoracic fascia, we micropunctured the lung tissue through the intact pleural space at functional residual capacity (FRC) and at volumes above FRC to evaluate the effect of increasing parenchymal stresses on pulmonary interstitial pressure (Pip). Pip was measured at a depth of approximately 230 microns from the pleural surface, at 50% lung height, in 12 anesthetized paralyzed rabbits oxygenated via a tracheal tube with 50% humidified O2. Pip was -10 +/- 1.5 cmH2O at FRC. At alveolar pressure of 5 and 10 cmH2O, lung volume increased by 8.5 and 19 ml and Pip decreased to -12.4 +/- 1.6 and -12.3 +/- 5 cmH2O, respectively. For the same lung volumes held by decreasing pleural surface pressure to about -5 and -8.5 cmH2O, Pip decreased to -17.4 +/- 1.6 and -23.8 +/- 5 cmH2O, respectively. Because Pip is more negative than pleural pressure, the data suggest that in intact pulmonary interstitium the pressure of the liquid phase is primarily set by the mechanisms controlling interstitial fluid turnover.     

Direct measurement of interstitial pulmonary pressure in in situ lung with intact pleural space

We developed an experimental approach to measure the pulmonary interstitial pressure with the micropuncture technique in in situ lungs with an intact pleural space. Experiments were done in anesthetized paralyzed rabbits that were oxygenated via an endotracheal tube with 50% humidified oxygen and kept in either the supine or the lateral position. A small area of an intercostal space was cleared of the intercostal muscles down to the endothoracic fascia. Subsequently a "pleural window" was opened by stripping the endothoracic fascia over a 0.2-cm2 surface and leaving the parietal pleura (approximately 10 microns thick). Direct micropuncture through the pleural window was performed with 2- to 3-microns-tip pipettes connected to a servo-null pressure-measuring system. We recorded pleural liquid pressure and, after inserting the pipette tip into the lung, we recorded interstitial pressure from subpleural lung tissue. Depth of recording for interstitial pressure averaged 263 +/- 122 (SD) microns. We report data gathered at 26, 53, and 84% lung height (relative to the most dependent portion of the lung). For the three heights, interstitial pressure was -9.8 +/- 3, -10.1 +/- 1.6, and -12.5 +/- 3.7 cmH2O, respectively, whereas the corresponding pleural liquid pressure was -3.4 +/- 0.5, -4.4 +/- 1, and -5.2 +/- 0.3 cmH2O, respectively.     

Effect of alveolar and pleural pressures on interstitial pressures in isolated dog lungs

We report the first direct measurements of perialveolar interstitial pressures in lungs inflated with negative pleural pressure. In eight experiments, we varied surrounding (pleural) pressure in a dog lung lobe to maintain constant inflation with either positive alveolar and ambient atmospheric pleural pressures (positive inflation) or ambient atmospheric alveolar and negative pleural pressures (negative inflation). Throughout, vascular pressure was approximately 4 cmH2O above pleural pressure. By the micropuncture servo-null technique we recorded interstitial pressures at alveolar junctions (Pjct) and in the perimicrovascular adventitia (Padv). At transpulmonary pressure of 7 cmH2O (n = 4), the difference of Pjct and Pady from pleural pressure of 0.9 +/- 0.4 and -1.1 +/- 0.2 cmH2O, respectively, during positive inflation did not significantly change (P less than 0.05) after negative inflation. After increase of transpulmonary pressure from 7 to 15 cmH2O (n = 4), the decrease of Pjct by 3.3 +/- 0.3 cmH2O and Pady by 2.0 +/- 0.4 cmH2O during positive inflation did not change during negative inflation. The Pjct-Pady gradient was not affected by the mode of inflation. Our measurements indicate that, in lung, when all pressures are referred to pleural or alveolar pressure, the mode of inflation does not affect perialveolar interstitial pressures.     

Gravity-dependent distribution of parietal subpleural interstitial pressure

Using liquid-filled catheters, we recorded, in 30 anesthetized, spontaneously breathing supine rabbits, the hydraulic pressure from the parietal subpleural interstitial space (Pspl). Through a small exposed area of parietal pleura a plastic catheter (1 mm ED), with a closed and smooth tip and several holes on the last centimeter, was carefully advanced between the muscular layer and the parietal pleura, tangentially to the pleural surface to reach the submesothelial layer. Simultaneous measurements of pleural liquid pressure (Pliq) were obtained from intrapleurally placed cannulas. End-expiratory Pspl decreased (became more negative) with increasing height (LH) according to the following: Pspl (cmH2O) = -1 - 0.4 LH (cm), the corresponding equation for Pliq being Pliq (cmH2O) = -1.5 - 0.7 LH (cm). Thus at end expiration a transpleural hydraulic pressure difference (Pliq-Pspl) developed at any height, increasing from the bottom to the top of the cavity as Pliq - Pspl (cmH2O) = -0.5 - 0.3 LH (cm). The Pliq-Pspl difference increased during inspiration due to the much smaller tidal change in Pspl than in Pliq. By considering the gravity-dependent distribution of the functional hydrostatic pressure in the systemic capillaries of the pleura (Pc) and the Pspl and Pliq values integrated over the respiratory cycle we estimated that on the average, the Pc-Pspl difference is sevenfold larger than the Pspl-Pliq difference.     

Pleural and extrapleural interstitial liquid pressure measured by cannulas and micropipettes

In 15 anesthetized apneic, oxygenated rabbits we simultaneously measured pleural liquid and interstitial extrapleural parietal pressures by using catheters and/or cannulas and micropipettes connected to a servonull system. With the animal in lateral posture, at an average recording height of 4.4 +/- 0.9 (SD) cm from the most dependent part of the cavity, the extrapleural catheter and the pleural cannula yielded -2.5 +/- 0.6 and -5.5 +/- 0.2 cmH2O; the corresponding values for micropipette readings in the two compartments were -2.4 +/- 0.6 and -5.4 +/- 0.4 cmH2O, respectively (not significantly different from those measured with catheters and cannulas). In the supine animal, interstitial extrapleural catheter pressure data obtained at recording heights ranging from 15 to 80% of pleural cavity lay on the identity line when plotted vs. the micropipette pressure values simultaneously gathered from the same tissues. We conclude that 1) micropipettes and catheters-cannulas yield similar results when recording from the same compartment and 2) the hydraulic pressure in the parietal extrapleural interstitium is less negative than that in the pleural space.     

Chest wall distortion and regional lung volume distribution in erect humans.

Using 133Xe measured the regional distribution of FRC and of boluses administered at FRC in seated subjects during relaxation, lateral compression of the lower rib cage, and contraction of the inspiratory muscles so that mouth pressure was 50 cmH2O subatmospheric. Lateral compression increased apex-to-base differences of volume and bolus distribution, suggesting an increase of the apex-to-base gradient of pleural surface pressure. Changes in rib cage shape were measured with magnetometers and were qualitatively similar to those associated with increases in apex-to-base difference of pleural surface pressure in animals. Inspiratory effort decreased apex-to-base difference in volume and induced a similar trend in bolus distribution. Though changes in the rib cage shape were directionally similar, they were much smaller than those associated with decreased pleural surface pressure gradients in animals, and the changes in regional volume we observed were more likely due to forces generated by diaphragmatic contraction. These results were compatible with the apex-to-base gradient of pleural pressure being strongly influenced by shape adaptation between lung and chest wall.     

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.     

Effects of lung inflation on pulmonary arterial blood volume in intact dogs.

The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.     

Lung expansion and the perialveolar interstitial pressure gradient

We have determined the combined effects of lung expansion and increased extravascular lung water (EVLW) on the perialveolar interstitial pressure gradient. In the isolated perfused lobe of dog lung, we measured interstitial pressures by micropuncture at alveolar junctions (Pjct) and in adventitia of 30- to 50-microns microvessels (Padv) with stopped blood flow at vascular pressure of 3-5 cmH2O. We induced edema by raising vascular pressures. In nonedematous lobes (n = 6, EVLW = 3.1 +/- 0.3 g/g dry wt) at alveolar pressure of 7 cmH2O, Pjct averaged 0.5 +/- 0.8 (SD) cmH2O and the Pjct-Padv gradient averaged 0.9 +/- 0.5 cmH2O. After increase of alveolar pressure to 23 cmH2O the gradient was abolished in nonedematous lobes, did not change in moderately edematous lobes (n = 9, EVLW = 4.9 +/- 0.6 g/g dry wt), and increased in severely edematous lobes (n = 6, EVLW = 7.6 +/- 1.4 g/g dry wt). Perialveolar interstitial compliance decreased with increase of alveolar pressure. We conclude that increase of lung volume may reduce perialveolar interstitial liquid clearance by abolishing the Pjct-Padv gradient in nonedematous lungs and by compressing interstitial liquid channels in edematous lungs.     

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.