Alveolar liquid pressure in excised edematous dog lung with increased static recoil

Alveolar liquid pressure (Pliq) was measured by micropipettes in conjunction with a servo-nulling pressure measuring system in isolated air-inflated edematous dog lungs. Pliq was measured in lungs either washed with a detergent (0.01% Triton X-100) or subjected to refrigeration for 2-3 days followed by ventilation for 3 h. At 55% of total lung capacity (TLC, the volume at a transpulmonary pressure (Ptp) of 25 cmH2O before treatment), in both the Triton-washed and the ventilated lung, Ptp increased from 5 to 11 cmH2O, whereas Pliq, decreased from -3 to -11 cmH2O relative to alveolar air pressure. Similar increases in Ptp and decreases in Pliq were obtained at higher lung volumes. Alveolar surface tension (T) was estimated from the Laplace equation for a spherical air-liquid interface, assuming that the radius of curvature varies as (volume)n, for -1/3 less than n less than 1/3. For uniform expansion of alveoli (n = 1/3), estimated T was 6 and 18 dyn/cm at 55 and 85% TLC, respectively, before treatment and increased to 23 and 40 dyn/cm following either Triton washing or ventilation. If pericapillary interstitial fluid pressure (Pi) equaled Pliq in edematous lungs, increases in T might reduce Pi and increase extravascular fluid accumulation in lungs made stiff by either Triton washing or cooling and ventilation using large tidal volumes.     

Parenchymal interdependence and airway response to methacholine in excised dog lobes

The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.     

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.     

Mechanics of edematous lungs.

Using the parenchymal marker technique, we measured pressure (P)-volume (P-V) curves of regions with volumes of approximately 1 cm3 in the dependent caudal lobes of oleic acid-injured dog lungs, during a very slow inflation from P = 0 to P = 30 cmH2O. The regional P-V curves are strongly sigmoidal. Regional volume, as a fraction of volume at total lung capacity, remains constant at 0.4-0.5 for airway P values from 0 to approximately 20 cmH2O and then increases rapidly, but continuously, to 1 at P = approximately 25 cmH2O. A model of parenchymal mechanics was modified to include the effects of elevated surface tension and fluid in the alveolar spaces. P-V curves calculated from the model are similar to the measured P-V curves. At lower lung volumes, P increases rapidly with lung volume as the air-fluid interface penetrates the mouth of the alveolus. At a value of P = approximately 20 cmH2O, the air-fluid interface is inside the alveolus and the lung is compliant, like an air-filled lung with constant surface tension. We conclude that the properties of the P-V curve of edematous lungs, particularly the knee in the P-V curve, are the result of the mechanics of parenchyma with constant surface tension and partially fluid-filled alveoli, not the result of abrupt opening of airways or atelectatic parenchyma.     

Indirect estimate of perimicrovascular pressure rise in edema in isolated zone 1 lung

To determine how liquid accumulation affects extra-alveolar perimicrovascular interstitial pressure, we measured filtration rate under zone 1 conditions (25 cmH2O alveolar pressure, 20 or 10 cmH2O vascular pressure) in isolated dog lung lobes in which all vessels were filled with autologous plasma. In the base-line condition, starting with normal extra-alveolar water content, filtration rate decreased by about one-half over 1 h as edema liquid slowly accumulated. We repeated each experiment after inducing edema (up to 100% lung weight gain). The absolute values and time course of filtration in the edema condition did not differ from base-line, i.e., the edema did not affect the time course of filtration. To compute the maximal initial and maximal change in extra-alveolar perimicrovascular pressure that occurred over each 1-h filtration study, we first assumed that the reflection coefficient is 0 in the Starling equation, then calculated perimicrovascular pressure and filtration coefficient from two equations with two unknowns. The mean filtration coefficient in 10 lobes is 0.063 g/(min X cmH2O X 100 g wet wt), and the initial perimicrovascular pressure is 3.9 cmH2O, rising by 4-7 cmH2O at 1 h. Finally we tested low protein perfusates and found the filtration rate was higher. We calculated an overall reflection coefficient = 0.44, a decrease in the initial perimicrovascular pressure to 1.9 cmH2O and a slightly lower increase after 1 h of edema formation, 2.2-6.6 cmH2O.     

Production mechanism of crackles in excised normal canine lungs

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.     

Measurement of interrupter resistance in rabbits exposed to methacholine aerosols.

We studied the effect of increasing airway resistance on equilibration of airway and alveolar pressure during passive expiratory airflow interruption. In 10 anesthetized and paralyzed rabbits, airway and alveolar pressures were compared before and after airway resistance was increased with methacholine. In all studies, airway pressure rose to equilibrate with alveolar pressure immediately after the interruption (delta Pinit) regardless of increases in airway resistance. The pressures then remained equal during the interruption while gradually increasing to plateau (delta Pdiff). Before methacholine exposure, delta Pdiff was small (0.6 +/- 0.3 cmH2O). Steady-state resistance calculated from the sum of delta Pinit and delta Pdiff was similar to airway resistance calculated from delta Pinit alone. After methacholine, increased airway resistance was accompanied by increased delta Pdiff (2.0 +/- 0.5 cmH2O), causing disproportionate increase in steady-state resistance. delta Pdiff increases were equal in the airway and alveoli, implying resistive changes distal to the sampled alveoli. Thus increasing airway resistance did not delay pressure equilibration across airways. However, increases in airway resistance were accompanied by tissue resistive changes that were greater than the increases in airway resistance.     

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.     

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.     

Growth rate of perivascular cuffs in liquid-inflated dog lung lobes

In the early stages of pulmonary edema, excess liquid leaving the pulmonary exchange vessels accumulates in the peribronchovascular interstitium where it forms large peribronchovascular cuffs. The peribronchovascular interstitium therefore acts as a reservoir to protect the air spaces from alveolar flooding. The rate of liquid accumulation and the liquid storage capacity of the cuffs determine how quickly alveolar flooding is likely to follow once edema formation has begun. To measure the rate and capacity of interstitial filling we inflated 11 isolated degassed dog lung lobes with liquid to an inflation pressure of 14 cmH2O (total lung capacity) for 1-300 min, then froze the lobes in liquid N2. We made photographs of 20 randomly selected 12 X 8-mm cross sections from each lobe and measured cuff volume from the photographs by point-counting. We found that cuff volume increased from 2.2% of air-space volume after 1 min of inflation to 9.3% after 300 min. To measure the driving pressure responsible for cuff formation we used micropipettes to measure subpleural interstitial liquid pressure at the hilum of three additional lobes. With liquid inflation pressure set to 14 cmH2O interstitial pressure rose exponentially to 11.5 cmH2O. Interstitial compliance calculated from our volume and pressure measurements equaled 0.09 ml X cmH2O-1 X g wet wt-1, a value similar to that measured in air-inflated lungs. Goldberg [Am. J. Physiol. 239 (Heart Circ. Physiol. 8): H189-H198, 1980] has likened interstitial filling to the charging of a capacitor, a process that follows a monoexponential time course.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mean airway pressure and mean alveolar pressure during high-frequency jet ventilation in rabbits

Mean airway pressure underestimates mean alveolar pressure during high-frequency oscillatory ventilation. We hypothesized that high inspiratory flows characteristic of high-frequency jet ventilation may generate greater inspiratory than expiratory pressure losses in the airways, thereby causing mean airway pressure to overestimate, rather than underestimate, mean alveolar pressure. To test this hypothesis, we ventilated anesthetized paralyzed rabbits with a jet ventilator at frequencies of 5, 10, and 15 Hz, constant inspiratory-to-expiratory time ratio of 0.5 and mean airway pressures of 5 and 10 cmH2O. We measured mean total airway pressure in the trachea with a modified Pitot probe, and we estimated mean alveolar pressure as the mean pressure corresponding in the static pressure-volume relationship to the mean volume of the respiratory system measured with a jacket plethysmograph. We found that mean airway pressure was similar to mean alveolar pressure at frequencies of 5 and 10 Hz but overestimated it by 1.1 and 1.4 cmH2O at mean airway pressures of 5 and 10 cmH2O, respectively, when frequency was increased to 15 Hz. We attribute this finding primarily to the combined effect of nonlinear pressure frictional losses in the airways and higher inspiratory than expiratory flows. Despite the nonlinearity of the pressure-flow relationship, inspiratory and expiratory net pressure losses decreased with respect to mean inspiratory and expiratory flows at the higher rates, suggesting rate dependence of flow distribution. Redistribution of tidal volume to a shunt airway compliance is thought to occur at high frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Pressure-flow behavior of pulmonary interstitium

A method to measure the pressure-flow behavior of the interstitium around large pulmonary vessels is presented. Isolated rabbit lungs were degassed, and the air spaces and vasculature were inflated with a silicon rubber compound. After the rubber had hardened the caudal lobes were sliced into 1-cm-thick slabs. Two chambers were bonded to opposite sides of a slab enclosing a large blood vessel and were filled with saline containing 3 g/dl albumin. The flow through the interstitium surrounding the vessel was measured at a constant driving pressure of 5 cmH2O and at various mean interstitial pressures. Flow decreased with a reduction of mean interstitial pressure and reached a limiting minimum value at approximately -9 cmH2O. The pressure-flow behavior was analyzed under the assumptions that the interstitium is a porous material described by a single permeability constant that increases with hydration and that the expansion of the interstitium with interstitial pressure was due to the elastic response of the surrounding rubber compound. This resulted in an interstitial resistance (reciprocal of permeability constant) of 1.31 +/- 1.03 (SD) cmH2O.h.cm-2 and a ratio of interstitial cuff thickness to vessel radius of 0.022 +/- 0.007 (SD), n = 11. The phenomenon of flow limitation was demonstrated by holding the upstream pressure constant at 15 cmH2O and measuring the flow while the downstream pressure was reduced. The flow was limited at downstream pressures below -10 cmH2O.     

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.     

Heterogeneity of mean alveolar pressure during high-frequency oscillations

Mean alveolar pressure may exceed mean airway pressure during high-frequency oscillations (HFO). To assess the magnitude of this effect and its regional heterogeneity, we studied six excised dog lungs during HFO [frequency (f) 2-32 Hz; tidal volume (VT) 5-80 ml] at transpulmonary pressures (PL) of 6, 10, and 25 cmH2O. We measured mean pressure at the airway opening (Pao), trachea (Ptr), and four alveolar locations (PA) using alveolar capsules. Pao was measured at the oscillator pump, wherein the peak dynamic head was less than 0.2 cmH2O. Since the dynamic head was negligible here, and since these were excised lungs, Pao thus represented true applied transpulmonary pressure. Ptr increasingly underestimated Pao as f and VT increased, with Pao - Ptr approaching 8 cmH2O. PA (averaged over all locations) and Pao were nearly equal at all PL's, f's, and VT's, except at PL of 6, f 32 Hz, and VT 80 ml, where (PA - Pao) was 3 cmH2O. Remarkably, mean pressure in the base exceeded that in the apex increasingly as f and VT increased, the difference approaching 3 cmH2O at high f and VT. We conclude that, although global alveolar overdistension assessed by PA - Pao is small during HFO under these conditions, larger regional heterogeneity in PA's exists that may be a consequence of airway branching angle asymmetry and/or regional flow distribution.     

Airway level at which edema liquid enters the air space of isolated dog lungs

To identify lung units associated with liquid leakage into the air space in high-pressure pulmonary edema, we perfused air-inflated dog lung lobes with albumin solution to fill the loose peribronchovascular interstitium. Next, we perfused the lobes for 90 s with fluorescent albumin solution then froze the lobes in liquid nitrogen. This procedure confined the fluorescent perfusate to the liquid flux pathway between the circulation and the air space and eliminated the previously filled peribronchovascular cuffs as a source of the fluorescence that entered the air space. We divided each frozen lobe into three horizontal layers and prepared fluorescence-microscopic sections of each layer. In the most apical layers where alveolar flooding was minimal, 10.6 +/- 21.0% (SD) of alveolar ducts were either fluorescence filled or air filled and continuous with fluorescence-filled alveoli. In the same layers, 11.0 +/- 19.0% of respiratory bronchioles were similarly labeled. No terminal bronchioles in these layers were fluorescence labeled. This suggested that the fluorescent albumin entered the air space across the epithelium of respiratory bronchioles, alveolar ducts, or their associated alveoli. To simulate an alternative explanation, i.e., that fluorescence first entered central airways then flowed into peripheral air spaces, we prepared two additional lobes that we first partially inflated with fluorescent albumin then filled to capacity with air. This pushed the fluorescent solution along the airways into the lung periphery. In these lobes the ciliary lining of bronchi and terminal bronchioles was fluorescence coated. By comparison, cilia in fluorescence-perfused lobes were not coated. We conclude that alveolar flooding in hydrostatic pulmonary edema occurs across the epithelium of alveolar ducts, respiratory bronchioles, or their associated alveoli.(ABSTRACT TRUNCATED AT 250 WORDS)     

Collateral flow resistance and time constants in dog and horse lungs

We studied collateral flow resistance in exsanguinated, excised lower lobes and accessory lobes of dog and horse lungs, respectively. A double lumen catheter obstructed a peripheral airway isolating a segment of the lobe. Oxygen flowed into the segment via a rotameter which measured flow (Vcoll) while the inner catheter recorded segment pressure (Ps). Gas delivered into the segment flowed out via collateral channels. Collateral flow resistance was calculated as (Ps - PL)/Vcoll, where PL = static transpulmonary pressure. Rcoll at PL = 20, 10, and 5 cm H2O averaged 0.24, 1.25, and 2.65 cmH2O.ml-1.s, respectively, in the dog, and 4.53, 6.00, and 12.62 cmH2O.ml-1.s in the horse. At a given PL, Rcoll measured during inflation. At constant PL, Rcoll increased with time at PL = 5 and 10 cmH2O, but was not time dependent at PL = 20 cmH2O. At constant PL, Rcoll increased at Vcoll increased. We conclude Rcoll is greater in horses than in dogs and is a function of PL, Ps - PL, and lung volume history in both species.     

Effect of alveolar liquid on distribution of blood flow in dog lungs.

Previous studies have shown that a shift in blood flow away from edematous regions does not occur until the alveoli contain liquid. The present experiments were designed to examine the separate effect of air space liquid, air space plus interstitial liquid, and reduced lung volume on blood flow. We found that reduced lung volume was not associated with significant changes in blood flow and that no systematic change in blood flow occurred when alveoli were filled with isosmotic liquid (autologous plasma). However, when hyposmotic liquid (dilute plasma) was instilled so that both the air space and the alveolar wall interstitial space were filled, blood flow was systematically reduced. This suggested that interstitial liquid was responsible raising vascular resistance in these experiments and that it might also be important in raising local vascular resistance in pulmonary edema. This latter hypothesis was tested in isolated perfused lobes where rapid freezing and quantitative histology showed that the number of open capillaries was significantly reduced in the liquid-filled alveoli (P less than 0.001). These observations suggest that interstitial pressure rises in pulmonary edema with the result that the transmural pressure of the alveolar vessels falls and vascular resistance is increased.     

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.     

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.