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.     

High lung volume increases stress failure in pulmonary capillaries.

We previously showed that when pulmonary capillaries in anesthetized rabbits are exposed to a transmural pressure (Ptm) of approximately 40 mmHg, stress failure of the walls occurs with disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. The present study was designed to test whether stress failure occurred more frequently at high than at low lung volumes for the same Ptm. Lungs of anesthetized rabbits were inflated to a transpulmonary pressure of 20 cmH2O, perfused with autologous blood at 32.5 or 2.5 cmH2O Ptm, and fixed by intravascular perfusion. Samples were examined by both transmission and scanning electron microscopy. The results were compared with those of a previous study in which the lung was inflated to a transpulmonary pressure of 5 cmH2O. There was a large increase in the frequency of stress failure of the capillary walls at the higher lung volume. For example, at 32.5 cmH2O Ptm, the number of endothelial breaks per millimeter cell lining was 7.1 +/- 2.2 at the high lung volume compared with 0.7 +/- 0.4 at the low lung volume. The corresponding values for epithelium were 8.5 +/- 1.6 and 0.9 +/- 0.6. Both differences were significant (P less than 0.05). At 52.5 cmH2O Ptm, the results for endothelium were 20.7 +/- 7.6 (high volume) and 7.1 +/- 2.1 (low volume), and the corresponding results for epithelium were 32.8 +/- 11.9 and 11.4 +/- 3.7. At 32.5 cmH2O Ptm, the thickness of the blood-gas barrier was greater at the higher lung volume, consistent with the development of more interstitial edema. Ballooning of the epithelium caused by accumulation of edema fluid between the epithelial cell and its basement membrane was seen at 32.5 and 52.5 cmH2O Ptm. At high lung volume, the breaks tended to be narrower and fewer were oriented perpendicular to the axis of the pulmonary capillaries than at low lung volumes. Transmission and scanning electron microscopy measurements agreed well. Our findings provide a physiological mechanism for other studies showing increased capillary permeability at high states of lung inflation.     

Differential degradation of matrix proteoglycans and edema development in rabbit lung

The specific role of solid extracellular matrix components in opposing development of pulmonary interstitial edema was studied in adult anesthetized rabbits by challenging the lung parenchyma with an intravenous injection of a bolus of collagenase or heparanase. In 10 rabbits, pulmonary interstitial pressure (Pip) was measured by micropuncture in control and up to 3 h after collagenase or heparanase intravenous injection. With respect to control (Pip= -9.3 +/- 1.5 cmH2O, n = 10), both treatments caused a significant increase of Pip and of the wet weight-to-dry weight lung ratio. However, while tissue matrix stiffness was maintained after 60 min of collagenase, as indicated by the attainment of a positive Pip peak (Pip= 4.5 +/- 0.3 cmH2O, n = 5), this mechanical response was lost with heparanase (Pip= -0.6 +/- 1.3 cmH2O, n = 5). Biochemical analysis performed on a separate rabbit group (n = 15) showed an increased extraction of uronic acid with both enzymes, indicating a progressive matrix fragmentation. Gel chromatography analysis of the proteoglycan (PG) families showed that 60 min of both enzymatic treatments left the large-molecular-weight PGs (versican) essentially unaffected. However, the heparan-sulfate PG fraction was significantly cleaved, as indicated by a significant increase of the smaller PG fragments with heparanase, but not with collagenase. Hence, present data suggest that the integrity of the heparan-sulfate PGs is required to maintain the three-dimensional architecture of the pulmonary tissue matrix and in turn to counteract tissue fluid accumulation in situations of increased fluid filtration.     

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.     

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.     

Inspiratory muscles during exercise: a problem of supply and demand

The capacity of inspiratory muscles to generate esophageal pressure at several lung volumes from functional residual capacity (FRC) to total lung capacity (TLC) and several flow rates from zero to maximal flow was measured in five normal subjects. Static capacity was 126 +/- 14.6 cmH2O at FRC, remained unchanged between 30 and 55% TLC, and decreased to 40 +/- 6.8 cmH2O at TLC. Dynamic capacity declined by a further 5.0 +/- 0.35% from the static pressure at any given lung volume for every liter per second increase in inspiratory flow. The subjects underwent progressive incremental exercise to maximum power and achieved 1,800 +/- 45 kpm/min and maximum O2 uptake of 3,518 +/- 222 ml/min. During exercise peak esophageal pressure increased from 9.4 +/- 1.81 to 38.2 +/- 5.70 cmH2O and end-inspiratory esophageal pressure increased from 7.8 +/- 0.52 to 22.5 +/- 2.03 cmH2O from rest to maximum exercise. Because the estimated capacity available to meet these demands is critically dependent on end-inspiratory lung volume, the changes in lung volume during exercise were measured in three of the subjects using He dilution. End-expiratory volume was 52.3 +/- 2.42% TLC at rest and 38.5 +/- 0.79% TLC at maximum exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Effect of dehydration on interstitial pressures in the isolated dog lung

We have determined the effect of dehydration on regional lung interstitial pressures. We stopped blood flow in the isolated blood-perfused lobe of dog lung at vascular pressure of approximately 4 cmH2O. Then we recorded interstitial pressures by micropuncture at alveolar junctions (Pjct), in perimicrovascular adventitia (Padv), and at the hilum (Phil). After base-line measurements, we ventilated the lobes with dry gas to decrease extravascular lung water content by 14 +/- 5%. In one group (n = 10), at constant inflation pressure of 7 cmH2O, Pjct was 0.2 +/- 0.8 and Padv was -1.5 +/- 0.6 cmH2O. After dehydration the pressures fell to -5.0 +/- 1.0 and -5.3 +/- 1.3 cmH2O, respectively (P less than 0.01), and the junction-to-advential gradient (Pjct-Padv) was abolished. In a second group (n = 6) a combination of dehydration and lung expansion with inflation pressure of 15 cmH2O further decreased Pjct and Padv to -7.3 +/- 0.7 and -7.1 +/- 0.7 cmH2O, respectively. Phil followed changes in Padv. Interstitial compliance was 0.6 at the junctions, 0.8 in adventitia, and 0.9 ml.cmH2O-1.100 g-1 wet lung at the hilum. We conclude, that perialveolar interstitial pressures may provide an important mechanism for prevention of lung dehydration.     

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.     

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.     

Sound transmission between 50 and 600 Hz in excised pig lungs filled with air and helium.

This study measured transit time (TT) and attenuation of sound transmitted through six pairs of excised pig lungs. Single-frequency sounds (50-600 Hz) were applied to the tracheal lumen, and the transmitted signals were monitored on the tracheal and lung surface using microphones. The effect of varying intrapulmonary pressure (Pip) between 5 and 25 cmH(2)O on TT and sound attenuation was studied using both air and helium (He) to inflate the lungs. From 50 to approximately 200 Hz, TT decreased from 4.5 ms at 50 Hz to 1 ms at 200 Hz (at 25 cmH(2)O). Between approximately 200 and 600 Hz, TT was relatively constant (1.1 ms at upper and 1.5 ms at lower sites). Gas density had very little effect on TT (air-to-He ratio of approximately 1.2 at upper sites and approximately 1 at lower sites at 25 cmH(2)O). Pip had marked effects (depending on gas and site) on TT between 50 and 200 Hz but no effect at higher frequencies. Attenuation was frequency dependent between 50 and 600 Hz, varying between -10 and -35 dB with air and -2 and -28 dB with He. Pip also had strong influence on attenuation, with a maximum sensitivity of 1.14 (air) and 0.64 dB/cmH(2)O (He) at 200 Hz. At 25 cmH(2)O and 200 Hz, attenuation with air was about three times higher than with He. This suggests that sound transmission through lungs may not be dominated by parenchyma but by the airways. The linear relationship between increasing Pip and increasing attenuation, which was found to be between 50 and approximately 100 Hz, was inverted above approximately 100 Hz. We suggest that this change is due to the transition of the parenchymal model from open to closed cell. These results indicate that acoustic propagation characteristics are a function of the density of the transmission media and, hence, may be used to locate collapsed lung tissue noninvasively.     

Influence of lung volume on pulmonary microvascular pressure-volume characteristics.

The pressure-volume (P-V) characteristics of the lung microcirculation are important determinants of the pattern of pulmonary perfusion and of red and white cell transit times. Using diffuse light scattering, we measured capillary P-V loops in seven excised perfused dog lobes at four lung volumes, from functional residual capacity (FRC) to total lung capacity (TLC), over a wide range of vascular transmural pressures (Ptm). At Ptm 5 cmH(2)O, specific compliance of the microvasculature was 8.6%/cmH(2)O near FRC, decreasing to 2.7%/cmH(2)O as lung volume increased to TLC. At low lung volumes, the vasculature showed signs of strain stiffening (specific compliance fell as Ptm rose), but stiffening decreased as lung volume increased and was essentially absent at TLC. The P-V loops were smooth without sharp transitions, consistent with vascular distension as the primary mode of changes in vascular volume with changes in Ptm. Hysteresis was small (0.013) at all lung volumes, suggesting that, although surface tension may set basal capillary shape, it does not strongly affect capillary compliance.     

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.     

Effect of lung volume on interrupter resistance in cats challenged with methacholine

To examine the effects of changes in lung volume on the magnitude of maximal bronchoconstriction, seven anesthetized, paralyzed, tracheostomized cats were challenged with aerosolized methacholine (MCh) and respiratory system resistance (Rss) was measured at different lung volumes using the interrupter technique. Analysis of the pressure changes following end-inspiratory interruptions allowed us to partition Rss into two quantities with the units of resistance, one (Rinit) corresponding to the resistance of the airways and the other (Rdif) reflecting the viscoelastic properties of the tissues of the respiratory system as well as gas redistribution following interruption of flow. Rinit and Rdif were used to construct concentration-response curves to MCh. Lung volume was increased by the application of 5, 10, and 15 cmH2O of positive end-expiratory pressure. The curve for Rinit reached a plateau in all cats, demonstrating a limit to the degree of MCh-induced bronchoconstriction. The mean value of Rinit (cmH2O.ml-1.s) for the group under control conditions was 0.011 and rose to 0.058 after maximal bronchoconstriction; the volume at which the flow was interrupted was 11.5 +/- 0.5 (SE) ml/kg above functional residual capacity (FRC). It then fell progressively to 0.029 at 21.2 +/- 0.8 ml/kg above FRC, 0.007 at 35.9 +/- 1.3 ml/kg above FRC, and 0.005 at 52.0 +/- 1.8 ml/kg above FRC. Cutting either the sympathetic or parasympathetic branches of the vagi had no significant effect on the lung volume-induced changes in MCh-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of increases in lung volume on clearance of aerosolized solute from human lungs

To study the effect of increases in lung volume on solute uptake, we measured clearance of 99mTc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosol (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH2O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.     

Effects of lung volume on maximal methacholine-induced bronchoconstriction in normal humans

We examined the effects of lung volume on the bronchoconstriction induced by inhaled aerosolized methacholine (MCh) in seven normal subjects. We constructed dose-response curves to MCh, using measurements of inspiratory pulmonary resistance (RL) during tidal breathing at functional residual capacity (FRC) and after a change in end-expiratory lung volume (EEV) to either FRC -0.5 liter (n = 5) or FRC +0.5 liter (n = 2). Aerosols of MCh were generated using a nebulizer with an output of 0.12 ml/min and administered for 2 min in progressively doubling concentrations from 1 to 256 mg/ml. After MCh, RL rose from a base-line value of 2.1 +/- 0.3 cmH2O. 1-1 X s (mean +/- SE; n = 7) to a maximum of 13.9 +/- 1.8. In five of the seven subjects a plateau response to MCh was obtained at FRC. There was no correlation between the concentration of MCh required to double RL and the maximum value of RL. The dose-response relationship to MCh was markedly altered by changing lung volume. The bronchoconstrictor response was enhanced at FRC - 0.5 liter; RL reached a maximum of 39.0 +/- 4.0 cmH2O X 1-1 X s. Conversely, at FRC + 0.5 liter the maximum value of RL was reduced in both subjects from 8.2 and 16.6 to 6.0 and 7.7 cmH2O X 1-1 X s, respectively. We conclude that lung volume is a major determinant of the bronchoconstrictor response to MCh in normal subjects. We suggest that changes in lung volume act to alter the forces of interdependence between airways and parenchyma that oppose airway smooth muscle contraction.     

Functional adaptation of diaphragm to chronic hyperinflation in emphysematous hamsters

Costal strips of diaphragmatic muscle obtained from animals with elastase-induced emphysema generate maximum tension at significantly shorter muscle fiber lengths than muscle strips from control animals. The present study examined the consequences of alterations in the length-tension relationship assessed in vitro on the pressure generated by the diaphragm in vivo. Transdiaphragmatic pressure (Pdi) and functional residual capacity (FRC) were measured in 22 emphysematous and 22 control hamsters 4-5 mo after intratracheal injection of pancreatic elastase or saline, respectively. In 12 emphysematous and 12 control hamsters Pdi was also measured during spontaneous contractions against an occluded airway. To allow greater control over muscle excitation, Pdi was measured during bilateral tetanic (50 Hz) electrical stimulation of the phrenic nerves in 10 emphysematous and 10 control hamsters. Mean FRC in the emphysematous hamsters was 183% of the value in control hamsters (P less than 0.01). During spontaneous inspiratory efforts against a closed airway the highest Pdi generated at FRC tended to be greater in control than emphysematous hamsters. When control hamsters were inflated to a lung volume approximating the FRC of emphysematous animals, however, peak Pdi was significantly greater in emphysematous animals (70 +/- 6 and 41 +/- 8 cmH2O; P less than 0.05). With electrophrenic stimulation, the Pdi-lung volume curve was shifted toward higher lung volumes in emphysematous hamsters. Pdi at all absolute lung volumes at and above the FRC of emphysematous hamsters was significantly greater in emphysematous compared with control animals. Moreover, Pdi continued to be generated by emphysematous hamsters at levels of lung volume where Pdi of control subjects was zero.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microvascular pressure profile in intact in situ lung.

We measured the microvascular pressure profile in lungs physiologically expanded in the pleural space at functional residual capacity. In 29 anesthetized rabbits a caudal intercostal space was cleared of its external and internal muscles. A small area of endothoracic fascia was surgically thinned, exposing the parietal pleura through which pulmonary vessels were clearly detectable under stereomicroscopic view. Pulmonary microvascular pressure was measured with glass micropipettes connected to a servo-null system. During the pressure measurements the animal was kept apneic and 50% humidified oxygen was delivered in the trachea. Pulmonary arterial and left atrial pressures were 22.3 +/- 1.5 and 1.6 +/- 1.5 (SD) cmH2O, respectively. The segmental pulmonary vascular pressure drop expressed as a percentage of the pulmonary arterial to left atrial pressure was approximately 33% from pulmonary artery to approximately 130-microns-diam arterioles, 4.5% from approximately 130- to approximately 60-microns-diam arterioles, approximately 46% from approximately 60-microns-diam arterioles to approximately 30-microns-diam venules, approximately 9.5% from 30- to 150-microns-diam venules, and approximately 7% for the remaining venous segment. Pulmonary capillary pressure was estimated at approximately 9 cmH2O.     

Influence of passive changes of lung volume on upper airways

The total upper airway resistances are modified during active changes in lung volume. We studied nine normal subjects to assess the influence of passive thoracopulmonary inflation and deflation on nasal and pharyngeal resistances. With the subjects lying in an iron lung, lung volumes were changed by application of an extrathoracic pressure (Pet) from 0 to 20 (+Pet) or -20 cmH2O (-Pet) in 5-cmH2O steps. Upper airway pressures were measured with two low-bias flow catheters, one at the tip of the epiglottis and the other in the posterior nasopharynx. Breath-by-breath resistance measurements were made at an inspiratory flow rate of 300 ml/s at each Pet step. Total upper airway, nasal, and pharyngeal resistances increased with +Pet [i.e., nasal resistance = 139.6 +/- 14.4% (SE) of base-line and pharyngeal resistances = 189.7 +/- 21.1% at 10 cmH2O of +Pet]. During -Pet there were no significant changes in nasal resistance, whereas pharyngeal resistance decreased significantly (pharyngeal resistance = 73.4 +/- 7.4% at -10 cmH2O). We conclude that upper airway resistance, particularly the pharyngeal resistance, is influenced by passive changes in lung volumes, especially pulmonary deflation.