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.     

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.     

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.     

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 stress pressure as a force to control liquid accumulation and maintain lung expansion

Total gas pressure in the pleural space is more subatmospheric than that in the alveolar cavity. This pressure difference minus elastic recoil pressure of the lung was termed stress pressure. We investigated the relationship between stress pressure and a force that would hold the lung against the chest wall to prevent accumulation of liquid. The condition was a pleural space with an enlarged pleural surface pressure. Dogs anesthetized with pentobarbital sodium were placed in a box maintained subatmospherically at approximately -30 cmH2O and breathed atmospheric air for 4 h. Liquid volume in the pleural space of the dogs was measured under conditions of thoracotomy. In the normal group, the volume of the pleural liquid was within the normal range of approximately 2.0 ml and the visceral and the parietal pleura made contact. In the pneumothorax group, established by injecting 50 ml of air into the pleural space, the liquid increased significantly in all cases by a mean value of approximately 12 ml. Thus pleural stress pressure seems to be an important force holding the lung against the chest wall and aiding in the control of accumulation of liquid in a more subatmospheric pleural space.     

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.     

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.     

Interstitial fluid pressure gradient measured by micropuncture in excised dog lung

We have directly measured lung interstitial fluid pressure at sites of fluid filtration by micropuncturing excised left lower lobes of dog lung. We blood-perfused each lobe after cannulating its artery, vein, and bronchus to produce a desired amount of edema. Then, to stop further edema, we air-embolized the lobe. Holding the lobe at a constant airway pressure of 5 cmH2O, we measured interstitial fluid pressure using beveled glass micropipettes and the servo-null method. In 31 lobes, divided into 6 groups according to severity of edema, we micropunctured the subpleural interstitium in alveolar wall junctions, in adventitia around 50-micron venules, and in the hilum. In all groups an interstitial fluid pressure gradient existed from the junctions to the hilum. Junctional, adventitial, and hilar pressures, which were (relative to pleural pressure) 1.3 +/- 0.2, 0.3 +/- 0.5, and -1.8 +/- 0.2 cmH2O, respectively, in nonedematous lobes, rose with edema to plateau at 4.1 +/- 0.4, 2.0 +/- 0.2, and 0.4 +/- 0.3 cmH2O, respectively. We also measured junctional and adventitial pressures near the base and apex in each of 10 lobes. The pressures were identical, indicating no vertical interstitial fluid pressure gradient in uniformly expanded nonedematous lobes which lack a vertical pleural pressure gradient. In edematous lobes basal pressure exceeded apical but the pressure difference was entirely attributable to greater basal edema. We conclude that the presence of an alveolohilar gradient of lung interstitial fluid pressure, without a base-apex gradient, represents the mechanism for driving fluid flow from alveoli toward the hilum.     

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.     

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.     

Effects of inspiratory resistance loading on lung fluid balance in awake sheep

Because pulmonary edema has been associated clinically with airway obstruction, we sought to determine whether decreased intrathoracic pressure, created by selective inspiratory obstruction, would affect lung fluid balance. We reasoned that if decreased intrathoracic pressure caused an increase in the transvascular hydrostatic pressure gradient, then lung lymph flow would increase and the lymph-to-plasma protein concentration ratio (L/P) would decrease. We performed experiments in six awake sheep with chronic lung lymph cannulas. After a base-line period, we added an inspiratory load (20 cmH2O) and allowed normal expiration at atmospheric pressure. Inspiratory loading was associated with a 12-cmH2O decrease in mean central airway pressure. Mean left atrial pressure fell 11 cmH2O, and mean pulmonary arterial pressure was unchanged; calculated microvascular pressure decreased 8 cmH2O. The changes that occurred in lung lymph were characteristic of those seen after other causes of increased transvascular hydrostatic gradient, such as increased intravascular pressure. Lung lymph flow increased twice base line, and L/P decreased. We conclude that inspiratory loading is associated with an increase in the pulmonary transvascular hydrostatic gradient, possibly by causing a greater fall in interstitial perimicrovascular pressure than in microvascular pressure.     

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.     

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.     

Steady-state pleural fluid flow and pressure and the effects of lung buoyancy

Both theoretical and experimental studies of pleural fluid dynamics and lung buoyancy during steady-state, apneic conditions are presented. The theory shows that steady-state, top-to-bottom pleural-liquid flow creates a pressure distribution that opposes lung buoyancy. These two forces may balance, permitting dynamic lung floating, but when they do not, pleural-pleural contact is required. The animal experiments examine pleural-liquid pressure distributions in response to simulated reduced gravity, achieved by lung inflation with perfluorocarbon liquid as compared to air. The resulting decrease in lung buoyancy modifies the force balance in the pleural fluid, which is reflected in its vertical pressure gradient. The data and model show that the decrease in buoyancy with perfluorocarbon inflation causes the vertical pressure gradient to approach hydrostatic. In the microgravity analogue, the pleural pressures would be toward a more uniform distribution, consistent with ventilation studies during space flight. The pleural liquid turnover predicted by the model is computed and found to be comparable to experimental values from the literature. The model provides the flow field, which can be used to develop a full transport theory for molecular and cellular constituents that are found in pleural fluid.     

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.     

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.     

A comparison of changes in esophageal pressure and regional juxtacardiac pressures

The relationship between esophageal pressure and juxtacardiac pressures was studied during positive end-expiratory pressure (PEEP) ventilation applied to both lungs or selectively to one lung. The experiments were performed in eight anesthetized dogs with balloon catheters in the esophagus and in the left and right pericardial and overlying pleural cavities and with an open-ended liquid-filled catheter in the pleural cavity. Bilateral PEEP (10, 20, and 30 cmH2O) caused progressive and similar increments in left and right pleural pressure. Selective PEEP, however, increased ipsilateral pleural balloon pressure more than contralateral pressure. The increase in ipsilateral pleural balloon pressure markedly exceeded the increase in esophageal pressure. There was a small increase in pleural open-ended catheter pressure that approximated the increase in esophageal pressure. During selective PEEP, pericardial balloon pressure remained uniform because of a decrease in ipsilateral pericardial transmural pressure. In conclusion, selective PEEP caused nonuniform increments in regional pleural balloon pressure. Left and right pericardial balloon pressure, however, increased uniformly with selective PEEP because of reduced ipsilateral pericardial transmural pressure. The esophageal balloon did not reflect the marked regional increments in pleural balloon pressure with selective PEEP and consistently underestimated the changes in pleural balloon pressure with general PEEP.     

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.     

Effect of airway and left atrial pressures on microcirculation of newborn lungs

To determine the effect of lung inflation and left atrial pressure on the hydrostatic pressure gradient for fluid flux across 20- to 60-microns-diam venules, we isolated and perfused the lungs from newborn rabbits, 7-14 days old. We used the micropuncture technique to measure venular pressures in some lungs and perivenular interstitial pressures in other lungs. For all lungs, we first measured venular or interstitial pressures at a constant airway pressure of 5 or 15 cmH2O with left atrial pressure greater than airway pressure (zone 3). For most lungs, we continued to measure venular or interstitial pressures as we lowered left atrial pressure below airway pressure (zone 2). Next, we inflated some lungs to whichever airway pressure had not been previously used, either 5 or 15 cmH2O, and repeated venular or interstitial pressures under one or both zonal conditions. We found that at constant blood flow a reduction of left atrial pressure below airway pressure always resulted in a reduction in venular pressure at both 5 and 15 cmH2O airway pressures. This suggests that the site of flow limitation in zone 2 was located upstream of venules. When left atrial pressure was constant relative to airway pressure, the transvascular gradient (venular-interstitial pressures) was greater at 15 cmH2O airway pressure than at 5 cmH2O airway pressure. These findings suggest that in newborn lungs edema formation would increase at high airway pressures only if left atrial pressure is elevated above airway pressure to maintain zone 3 conditions.     

Filtration profile in isolated zone 1 and zone 3 dog lungs at constant high alveolar pressure

We measured the rate of liquid filtration in isolated dog lung lobes inflated to a constant alveolar pressure of 25 cmH2O and with all open vessels filled with plasma. We measured lung weight gain at vascular pressures ranging from 5 to 40 cmH2O relative to pleural pressure. We confirmed that under zone 1 conditions the "arterial" and "venous" extra-alveolar segments have essentially the same filtration characteristics. Using the combined extra-alveolar vascular system, we determined when recruitment of filtration surface area occurred as we increased vascular pressure from 0 to 40 cmH2O. Based on an abrupt increase in filtration rate as vascular pressure approached the zone 1/3 boundary, we infer that a sudden recruitment of exchange surface area occurred at that point. Based on the slopes of the zone 1 and zone 3 filtration profiles, we conclude that extra-alveolar vascular segments contribute approximately 25% of total to filtration in the lung under zone 3 conditions, although the exact vessels filtering under zone 1 conditions have yet to be determined. Our analysis of the data supports the concept that there is a difference in the perimicrovascular pressure around alveolar and extra-alveolar vessels, which in part may account for the apparent high filtration fraction apportioned to extra-alveolar vessels.