Saline-filled Lungs Research Articles

New insight into air flow distribution in alveoli based on air- and saline-filled lungs

Understanding flow distributions in human lungs has attracted significant attention since the last few decades. However, there are still large discrepancies between different studies in the distribution of air flow into alveoli at different generations of bifurcation. In this study, a new method has been developed to calculate expansion ratio of alveoli and ratio of alveolar to ductal flow rate at different generations for air- and saline-filled lungs. The effects of alveolar number, breathing period, lung tidal volume, and surface tension are examined. It is found that the expansion ratio of alveoli varies significantly at different generations in the saline-filled lungs. For the air-filled lung, the expansion ratio of individual alveolus remains constant for different generations. The current study provides new data on the flow rate ratios which is critical for understanding flow distributions and flow behaviors in alveoli. Surface tension in alveoli and alveolar number has obvious effects on the value of flow ratio. The current study sheds new light into the flow behavior in lungs and lays the foundation for detailed study on flow and particle transport characteristics in human lungs.

Biophysical determinants of alveolar epithelial plasma membrane wounding associated with mechanical ventilation

Mechanical ventilation may cause harm by straining lungs at a time they are particularly prone to injury from deforming stress. The objective of this study was to define the relative contributions of alveolar overdistension and cyclic recruitment and "collapse" of unstable lung units to membrane wounding of alveolar epithelial cells. We measured the interactive effects of tidal volume (VT), transpulmonary pressure (PTP), and of airspace liquid on the number of alveolar epithelial cells with plasma membrane wounds in ex vivo mechanically ventilated rat lungs. Plasma membrane integrity was assessed by propidium iodide (PI) exclusion in confocal images of subpleural alveoli. Cyclic inflations of normal lungs from zero end-expiratory pressure to 40 cmH2O produced VT values of 56.9 ± 3.1 ml/kg and were associated with 0.12 ± 0.12 PI-positive cells/alveolus. A preceding tracheal instillation of normal saline (3 ml) reduced VT to 49.1 ± 6 ml/kg but was associated with a significantly greater number of wounded alveolar epithelial cells (0.52 ± 0.16 cells/alveolus; P < 0.01). Mechanical ventilation of completely saline-filled lungs with saline (VT = 52 ml/kg) to pressures between 10 and 15 cmH2O was associated with the least number of wounded epithelial cells (0.02 ± 0.02 cells/alveolus; P < 0.01). In mechanically ventilated, partially saline-filled lungs, the number of wounded cells increased substantially with VT, but, once VT was accounted for, wounding was independent of maximal PTP. We found that interfacial stress associated with the generation and destruction of liquid bridges in airspaces is the primary biophysical cell injury mechanism in mechanically ventilated lungs.

Role of aquaporin-4 in airspace-to-capillary water permeability in intact mouse lung measured by a novel gravimetric method.

The mammalian peripheral lung contains at least three aquaporin (AQP) water channels: AQP1 in microvascular endothelia, AQP4 in airway epithelia, and AQP5 in alveolar epithelia. In this study, we determined the role of AQP4 in airspace-to-capillary water transport by comparing water permeability in wild-type mice and transgenic null mice lacking AQP1, AQP4, or AQP1/AQP4 together. An apparatus was constructed to measure lung weight continuously during pulmonary artery perfusion of isolated mouse lungs. Osmotically induced water flux (J(v)) between the airspace and capillary compartments was measured from the kinetics of lung weight change in saline-filled lungs in response to changes in perfusate osmolality. J(v) in wild-type mice varied linearly with osmotic gradient size (4.4 x 10(-5) cm(3) s(-1) mOsm(-1)) and was symmetric, independent of perfusate osmolyte size, weakly temperature dependent, and decreased 11-fold by AQP1 deletion. Transcapillary osmotic water permeability was greatly reduced by AQP1 deletion, as measured by the same method except that the airspace saline was replaced by an inert perfluorocarbon. Hydrostatically induced lung edema was characterized by lung weight changes in response to changes in pulmonary arterial inflow or pulmonary venous outflow pressure. At 5 cm H(2)O outflow pressure, the filtration coefficient was 4.7 cm(3) s(-1) mOsm(-1) and reduced 1.4-fold by AQP1 deletion. To study the role of AQP4 in lung water transport, AQP1/AQP4 double knockout mice were generated by crossbreeding of AQP1 and AQP4 null mice. J(v) were (cm(3) s(-1) mOsm(-1) x 10(-5), SEM, n = 7-12 mice): 3.8 +/- 0. 4 (wild type), 0.35 +/- 0.02 (AQP1 null), 3.7 +/- 0.4 (AQP4 null), and 0.25 +/- 0.01 (AQP1/AQP4 null). The significant reduction in P(f) in AQP1 vs. AQP1/AQP4 null mice was confirmed by an independent pleural surface fluorescence method showing a 1.6 +/- 0.2-fold (SEM, five mice) reduced P(f) in the AQP1/AQP4 double knockout mice vs. AQP1 null mice. These results establish a simple gravimetric method to quantify osmosis and filtration in intact mouse lung and provide direct evidence for a contribution of the distal airways to airspace-to-capillary water transport.

Analysis of stress distribution in the alveolar septa of normal and simulated emphysematic lungs

The alveolar septum consists of a skeleton of fine collagen and elastin fibers, which are interlaced with a capillary network. Its mechanical characteristics play an important role in the overall performance of the lung. An alveolar sac model was developed for numerical analysis of the internal stress distribution and septal displacements within the alveoli of both normal and emphysematic saline-filled lungs. A scanning electron micrograph of the parenchyma was digitized to yield a geometric replica of a typical two-dimensional alveolar sac. The stress-strain relationship of the alveolar tissue was adopted from experimental data. The model was solved by using commercial finite-element software for quasi-static loading of alveolar pressure. Investigation of the state of stresses and displacements in a healthy lung simulation yielded values that compared well with experimentally reported data. Alteration of the mechanical characteristics of the alveolar septa to simulate elastin destruction in the emphysematic model induced significant stress concentrations (e.g., at a lung volume of 60% total capacity, tensions at certain parts in an emphysematic lung were up to 6 times higher than those in a normal lung). The combination of highly elevated stress sites together with the cyclic loading of breathing may explain the observed progressive damage to elastin fibers in emphysematic patients.

Paraquat poisoning: an experimental model of dose-dependent acute lung injury due to surfactant dysfunction.

Since the most characteristic feature of paraquat poisoning is lung damage, a prospective controlled study was performed on excised rat lungs in order to estimate the intensity of lesion after different doses. Twenty-five male, 2-3-month-old non-SPF Wistar rats, divided into 5 groups, received paraquat dichloride in a single intraperitoneal injection (0, 1, 5, 25, or 50 mg/kg body weight) 24 h before the experiment. Static pressure-volume (PV) curves were performed in air- and saline-filled lungs; an estimator of surface tension and tissue works was computed by integrating the area of both curves and reported as work/ml of volume displacement. Paraquat induced a dose-dependent increase of inspiratory surface tension work that reached a significant two-fold order of magnitude for 25 and 50 mg/kg body weight (P < 0.05, ANOVA), sparing lung tissue. This kind of lesion was probably due to functional abnormalities of the surfactant system, as was shown by the increase in the hysteresis of the paraquat groups at the highest doses. Hence, paraquat poisoning provides a suitable model of acute lung injury with alveolar instability that can be easily used in experimental protocols of mechanical ventilation.

Lung Tissue Resistance Measured in Saline-Filled Guinea Pig Lungs by Micropuncture

Lung tissue resistance (Rti) measured in air-filled guinea pig lungs by the alveolar capsule technique was a large part of total lung resistance (Rl), and we wondered whether similar results applied to saline-filled lungs. We used the micropuncture method to measure alveolar pressure (Palv) in saline-filled lungs of 21 guinea pigs. Palv and airway opening pressure (Pao) were measured before and after a sudden interruption of flow during an inflation or deflation maneuver. On stopping flow, there was an immediate large change in Pao followed by a smaller slower change in Pao. Palv was nearly constant immediately after flow interruption but followed the slower change in Pao. The initial change in Pao on flow interruption was interpreted as the resistive pressure loss in the airways. The small change in Pao and Palv was interpreted as the pressure loss caused by tissue stress adaptation. Airway resistance (R(aw)) and Rti were obtained by dividing the pressure losses by the flow before the interruption. Rl was the sum of R(aw) and Rti. The calcium blocker nifedipine reduced both R(aw) and Rti and abolished the difference in Rti between inflation and deflation. Values of Rti were 10-29% of Rl. However, with correction for viscosity, Rti predicted in air-filled lungs would dominate Rl.

Relationships between alveolar size and fibre distribution in a mammalian lung alveolar duct model.

A finite element model, comprising an assemblage of tetrakaidecahedra or truncated octahedra, is used to represent an alveolar duct unit. The dimensions of the elastin and collagen fibre bundles, and the surface tension properties of the air-liquid interfaces, are based on available published data. Changes to the computed static pressure-volume behavior with variation in alveolar dimensions and fibre volume densities are characterized using distensibility indices (K). The air-filled lung distensibility (Ka) decreased with a reduction in the alveolar airspace length dimensions and increased with a reduction of total fibre volume density. The saline-filled lung distensibility (Ks) remained constant with alveolar dimensions and increased with decreasing total fibre volume density. The degree of geometric anisotropy between the duct lumen and alveoli was computed over pressure-volume cycles. To preserve broadly isotropic behavior, parenchyma with smaller alveolar airspace length dimensions required higher concentrations of fibres located in the duct and less in the septa in comparison with parenchyma of larger airspace dimensions.

Strain-induced growth of the immature lung.

To investigate the relationship between strain and postnatal lung growth, two groups of weanling ferrets were tracheotomized: the study group was exposed for 2 wk to a continuous positive airway pressure (CPAP) of 6 cmH2O and the other group was exposed to atmospheric pressure (control). Total lung capacity after 2 wk was approximately 40% higher in the CPAP-exposed animals than in the control animals (n = 19 for the control group and 18 for the study group; P < 0.01). CPAP exposure was also associated with increases in lung weight and total lung protein and DNA contents. Lung recoil, measured in a subgroup of animals, was characterized by air-filled and saline-filled static expiratory pressure-volume curves. Neither in the air-filled lungs nor saline-filled lungs was there a significant difference between CPAP-exposed and control animals in lung recoil at equal fractions of total lung capacity. These data indicate that mechanical strain was associated with an acceleration of lung growth in immature ferrets. The preservation of volume-corrected lung recoil and the expected contribution of surface forces and tissue forces to lung recoil in CPAP-exposed animals suggest that this response did not involve simple lung distension but included a remodeling of the lung parenchyma.

The mechanical behavior of a mammalian lung alveolar duct model.

A model for the mechanical properties of an alveolar duct is analyzed using the finite element method. Its geometry comprises an assemblage of truncated octahedral alveoli surrounding a longitudinal air duct. The amounts and distributions of elastin and collagen fiber bundles, modeled by separate stress-strain laws, are based upon published data for dogs. The surface tension of the air-liquid interface is modeled using an area-dependent relationship. Pressure-volume curves are computed that compare well with experimental data for both saline-filled and air-filled lungs. Pressure-volume curves of the separate elastin and collagen fiber contributions are similar in form to the behavior of saline-filled lungs treated with either elastase or collagenase. A comparison with our earlier model, based upon a single alveolus, shows the duct to have a behavior closer to reported experimental data.

Disturbance of alveolar lining layer: effects on alveolar microstructure

To further study the influence of altered surface tensions on alveolar micromechanics, we analyzed the structure-function relationships in excised rabbit lungs filled with or rinsed by a fluorocarbon (approximately 15 mN/m) or by hexadecane (approximately 25 mN/m). The lungs were fixed and dehydrated by vascular perfusion, and the tissue samples were analyzed by light, transmission, and scanning electron microscopy. We made three observations. 1) Pressure-volume (P-V) loops hexadecane-filled lungs are shifted to the left and coincide with those of saline-filled lungs, indicating near-zero interfacial tension. In accordance, the alveolar microstructure and surface area of hexadecane-filled lungs resemble those of saline-filled lungs. 2) The P-V loops of fluorocarbon-filled lungs are not shifted to the left but coincide with those of fluorocarbon-rinsed lungs. Under both conditions, the alveolar microstructure is qualitatively identical and the alveolar surface areas are markedly reduced compared with normal air-filled lungs. These findings show that fluorocarbon-filled or fluorocarbon-rinsed lungs are subjected to similar interfacial tensions at the alveolar level. 3) Hexadecane-rinsed lungs show a pear-shaped P-V curve and a complex surface texture of peripheral air spaces. These results, together with in vitro observations, suggest a metamorphic interplay between lung surfactant and hexadecane in lining the surface and determining the surface tension. Evidently, the effects of foreign liquids introduced into the lung on the structure-function relationship cannot accurately be predicted from their in vitro surface tensions. This fact should be considered in the development of artificial surfactants.

The role of surfactant in the static lung mechanics of the lizard Ctenophorus nuchalis

We previously showed that the lung of the central Australian lizard, Ctenophorus nuchalis, contains a large amount of surfactant, the composition of which varies with body temperature. We now show that the specific compliance of the lungs of these lizards remains constant regardless of whether they were maintained at 10, 18, 27, 37 or 43°C for 4 hours. In contrast, the opening pressure was constant up to 27°C, but decreased at 37 and 43°C. When we lavaged the lungs in situ to remove the majority of surfactant, specific compliance decreased while opening pressure increased. The lungs of C. nuchalis are essentially two bubbles, with the left one larger at low and intermediate volumes. After collapsing both lungs, the larger left lung always inflated first. However, following lavage the smaller right lung inflated first. As the larger lung, when collapsed, would have a much greater area of epithelial contact, this result is consistent with surfactant acting as an ‘antiglue’. During deflation the smaller lung collapsed first, consistent with the law of Laplace. Compliance did not change in the saline-filled lung suggesting that the gas-liquid interface does not play a major role. We conclude that in the lungs of these lizards, surfactant is acting as an antiglue. This might be important during periods of apnea at low body temperatures, when residual volume is small and epithelial surfaces may come into contact.

Effects of repeated cycles of starvation and refeeding on lungs of growing rats.

Adult male rats were subjected to four cycles of mild starvation (2 wk) and refeeding (1 wk) and were compared with a fed group. Starvation was induced by giving rats one-third of their measured daily food consumption. During each starvation cycle, rats lost approximately 20% of their body weight. Despite catch-up growth and overall weight gain, starved rats had lower final body weight than fed rats. Lung dry weight and lung volumes were also reduced in the starved group. The mechanical properties of air- and saline-filled lungs did not change significantly with repeated cycles of starvation. Mean linear intercept was similar in the two groups, but alveolar surface area was reduced in the starved rats. Total content of crude connective tissue and concentration per lung dry weight of hydroxyproline and crude connective tissue were reduced in starved rats. We conclude that lung growth is retarded in growing rats subjected to repeated cycles of mild starvation and refeeding, as manifested by smaller lung volume and reduced alveolar surface area. Because alveolar size is unchanged, a reduced number of alveoli is most likely responsible for decreased lung volumes.

Effect of temperature on the biaxial mechanics of excised lung parenchyma of the dog.

The influence of temperature on the mechanical properties of excised saline-filled lung parenchyma of the dog was studied at low lung volume. The motivation of this study was to determine whether lung tissue material without the influence of surface tension undergoes a phase transition in the 20-40 degrees C range, as does synthetic elastin studied by Urry in 1984-1986. Dynamic biaxial and uniaxial tensile tests were done, and strain vs. Lagrangian stress curves were recorded during slow cooling and heating between 40 and 10 degrees C. To emphasize the effects of elastin, strains (defined as stretch ratio minus one) were kept below 30%. A slight decrease in compliance occurred with cooling over the entire temperature range. This effect may be attributed to collagen. It was accompanied by a gradual increase in length as the tissue cooled, an effect that may be attributed to elastin. This process was partially reversible with reheating. However, this effect is in contrast with the sudden drastic change in mechanical properties of synthetic elastin described by Urry. Hysteresis, creep, and stress relaxation were small at these low strains. Possible causes of these effects are discussed.

Microscopic vs. macroscopic deformation of the pulmonary alveolar duct.

The stretch of the perimeters of alveolar ducts was measured at the surface of saline-filled specimens of human and dog lung parenchyma that were stretched biaxially. The microscopic stretch of these ducts was measured at several levels of isotropic biaxial macroscopic stretch of the parenchyma with stretch ratio (lambda x = lambda y) in the range of 1.20-1.40, which roughly corresponds to tidal breathing in humans and dogs. Alveolar walls were found to be load-carrying elements in the saline-filled lung, as seen by their straightness at all levels of stretch. Quantitatively, let l, A, L, and S denote, respectively, the duct perimeter length and area and the parenchymal target perimeter and area in the deformed state and lo, Ao, Lo, and So the corresponding variables in the undeformed state. The microscopic stretch ratio of the ducts (l/lo) was found to be approximately 4% larger than the macroscopic stretch ratio (L/Lo) in human lung and approximately 10% larger in dog lung. The microscopic area ratio of the ducts (A/Ao) was found to be approximately 10% larger than the macroscopic area ratio (S/So) in human lung and approximately 22% larger in dog lung. Ducts within human parenchyma were seen to be about twice as stiff as ducts within dog parenchyma over the range of macroscopic stretch studied. This correlates with the volume fractions of collagen and elastin being higher in the human lung than in dog lung. The observed nonuniformity in strain field at the microstructural level suggests the need to include a force balance between alveolar ducts and septal walls when modeling the mechanics of saline-filled parenchyma.

Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats

Rats with established monocrotaline (MCT)-induced pulmonary hypertension also exhibit a profound increase in lung resistance (RL) and a decrease in lung compliance. Because airway/lung dysfunction could precede and influence the evolution of MCT-induced pulmonary vascular disease, it is important to establish the temporal relationship between development of pulmonary hypertension and altered ventilatory function in MCT-treated rats. To resolve this issue, we segregated 47 young Sprague-Dawley rats into four groups: control (n = 13), MCT1 (n = 9), MCT2 (n = 11), and MCT3 (n = 14). Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study. At 1 wk after MCT, significant increases in RL and alveolar wall thickness were observed, as was a significant decrease in carbon monoxide diffusing capacity (DLCO). Medial thickness of pulmonary arteries (50-100 microns OD) and right ventricular hypertrophy were not observed until 2 and 3 wk post-MCT, respectively. Coincident with the right ventricular hypertrophy at 3 wk post-MCT were decreased DLCO and increased alveolar wall thickness and lung dry weight. Pressure-volume curves of air-filled and saline-filled lungs showed marked rightward shifts during the 1st and 2nd wk after MCT administration and then decreased at the 3rd wk. These data suggest that MCT-induced alterations in airway/lung function preceded those of pulmonary vasculature and, therefore, implicate airway/lung dysfunctions as potentially contributing to the later development of pulmonary vascular abnormalities.

Surface and Tissue Forces, Surfactant Protein A, and the Phospholipid Components of Pulmonary Surfactant in Bleomycin-induced Pulmonary Fibrosis in the Rat

Administration of bleomycin to animals results in an alteration of the pressure-volume relationship of the lungs with an increased elastic recoil at any given volume. We sought to evaluate the relative importance of surface forces to elastic recoil by comparing the differences between the air and saline pressure-volume curves. The difference in elastic recoil between air- and saline-filled lungs was altered in bleomycin-treated rats when elastic recoil was compared at 35% of predicted TLC or at 80% of observed TLC. This pressure difference was present both during the early phase (Days 4 and 7) of the injury and acute inflammation as well as during the later phase (Days 14 to 28) when there was chronic inflammation and an elevation in the lung hydroxyproline content. The total amount of phospholipids recovered in lavage was decreased at Day 4 and increased more than 2.5-fold over saline-instilled control animals at Days 21 and 28. The percentage of phosphatidylglycerol was reduced and that of phosphatidylinositol increased. There was no consistent change in the percentage of phosphatidylcholine that was disaturated. The amount of surfactant protein A (SP-A) did not change during the course of the experiment and was not a useful independent marker of alveolar injury or changes in pulmonary compliance. The ratio of SP-A to total phospholipid decreased 14 to 28 days after instillation of bleomycin. These results support the hypothesis that individual components of surfactant are independently regulated and indicate that SP-A content in lavage is insensitive to lung injury and repair.

Effects of postnatal dexamethasone treatment on development of alveoli in adult rats.

We compared the effects of dexamethasone given to rats from age 4 to 14 days, on alveolar development at age 99 days. Judged by similar nose-to-tail length and body weight, somatic growth was not altered by dexamethasone treatment. Lung volumes in both air- and saline-filled lungs and mean chord length (Lm) were increased, whereas alveolar surface area (Sa) and surface-to-volume ratio (S/V) were diminished in dexamethasone-treated adult rats. These changes were associated with a significant reduction in DNA content and concentration but larger protein/DNA and RNA/DNA ratios in the lungs of treated rats. We conclude that dexamethasone treatment during the critical period of septation in rats impairs alveolar formation, which persists until adulthood and leads to larger and less complex gas-exchange regions. Inhibition of DNA synthesis due to dexamethasone may be responsible for its effects on alveolar development. Larger lung volumes in treated rats are, most likely, related to larger air space dimensions.

Airway resistance measured in liquid-trapped guinea pig lungs by micropuncture.

We studied the relationship between bronchoconstriction and the degree of trapping in saline-filled lungs isolated from guinea pigs postmortem after rapid exsanguination. Airway resistance was measured in nine lungs, and in five lungs the site of airway narrowing was located radiographically. Animals were anesthetized with pentobarbital sodium, degassed by O2 absorption, then rapidly exsanguinated when O2 absorption was almost complete. Liquid trapping was assessed from the pressure-volume behaviour measured in saline-filled lungs. During a slow deflation from maximum volume, alveolar liquid pressure (Palv) was measured by the micropipette-servonulling method, airway opening pressure (Pao) by a strain gauge, and flow rate (Q) by weighing a reservoir connected to the airway. Airway resistance (Raw) was calculated at different lung volumes from the relationship: Raw = (Palv-Pao)/Q. In untreated lungs, Raw and fluid trapping were relatively high, and severe bronchoconstriction occurred at the level of the main stem and lobar bronchi. Nifedipine infusion reduced Raw 40-fold and decreased trapping. Raw was further reduced 10-fold and fluid trapping was minimal in lungs pretreated with nifedipine before exsanguination. Results suggest a close association between bronchoconstriction and fluid trapping in guinea pig lungs.

Effects of streptozotocin-induced diabetes on lung mechanics and biochemistry in rats

Young and adult rats were given a single intraperitoneal injection of 75 mg/kg streptozotocin in citrate buffer and were compared with age- and weight-matched controls that received an equal volume of buffer alone. Studies done 8 wk after the injections showed that final body weight, lung dry weight, lung DNA content, and air and saline lung volumes were significantly lower in both young and adult diabetic rats compared with the controls. In young diabetic rats, volume-pressure (V-P) curves expressed as percent maximal lung volume (%MLV) were shifted downward and to the right of those in young control rats at 5 cmH2O transpulmonary pressure (PL) for air and at 4, 6, and 8 cmH2O PL for saline-filled lungs; specific lung compliance (CL) values obtained from both air and saline V-P curves were significantly reduced, and concentration of hydroxyproline relative to DNA was significantly increased. In adult diabetic rats, V-P curves expressed in %MLV, CL values, and concentrations of protein and hydroxyproline were similar to those in adult control rats. We conclude that in both young and adult rats, diabetic state leads to somatic and lung growth retardation. In addition in young diabetic rats lung distensibility is decreased. An increase in the concentration of some connective tissue proteins may be responsible for the latter observation.

Fluid trapping in postmortem guinea pig lungs.

To examine severe bronchoconstriction obstructing airways in the fluid-filled postmortem guinea pig lung, lungs were infused and deflated with isotonic solution following exsanguination. Guinea pigs were classified into 2 groups: young and mature, and each group was further classified into 2 subgroups: those receiving saline (Ca2+-free) and Tyrode's (Ca2+-containing) solutions. Each subgroup consisted of 7-8 animals. No significant change in total lung capacity from the baseline (prior to exsanguination) air value was observed in any subgroup within the experimental period of 60 min. However, both deflation volume (DV) and inflation volume (IV) decreased gradually with time; these decreases were larger in the saline-filled lungs than those of lungs infused with Tyrode's solution at 20-30 min. In the Tyrode's solution-filled lungs, larger decreases in DV and IV were found in the mature animals than in the young animals at 15-20 min. Trapped fluid volume (VT) increased gradually with time and reached mean values ranging from 9.1 to 11.5 times the baseline value at 60 min. No significant difference in VT between subgroups was observed. At any given time in all animals, the increase in VT was always equal to or larger than the decrease in DV or IV. Fluid cuffing around vessels and airways was demonstrated in the saline, but not in the air-filled lung. The data suggest that severe bronchoconstriction obstructing airways did not occur in postmortem fluid-filled guinea pig lungs. Dilution of mediators may be responsible for eliminating postmortem severe airway spasm and swelling of interstitium may induce the temporal increase in trapped volume in the fluid-filled lung.