Saline-filled Lungs Research Articles

Lung mechanics, cellularity, and surfactant after prenatal starvation in guinea pigs.

Prenatal starvation in the guinea pig causes reduced pulmonary diffusing capacity and retarded alveolarization among neonates. To study the impact of such starvation on biochemical and mechanical properties of the neonatal lung, pregnant guinea pigs were fed ad libitum throughout gestation or starved with 50% rations during their last trimester. Neonatal body weight was 35% less due to starvation, and dry lung weight, DNA, and protein contents were decreased 26, 36, and 31%, respectively (P less than 0.001 for all). Hematological data indicated no anemia, hypoproteinemia, or altered glucocorticoid levels due to starvation. Total surfactant phospholipids in these neonates were reduced 61% in lavage and 35% in the neonatal lung tissue, although surfactant compositions were similar to controls. Specific lung compliance in the air-filled lungs was not altered, but the saline-filled lungs were more distensible over deflation pressures of 9-18 cmH2O (transpulmonary). Although starvation retarded both lung cellularity and surfactant, only that portion of lung elastic recoil attributable to tissue forces was affected.

Static mechanics of excised whole lung: theoretical framework and experimental studies.

A theoretical framework is presented in which to view models of static pulmonary mechanics. To test common simplifying assumptions of these models, we performed a set of experiments using normal lungs excised from dogs. Transpulmonary pressure (Ptp) and lung volume (VL) were measured for air-filled lungs in air and saline-filled lungs in saline during stepwise-static deflations at different vascular volumes and temperatures. Simultaneously, we measured displacements between points on the lung surface. Changes in vascular volume shift the location but not the shape of the Ptp-VL relationship. As long as the vascular pressure is in the normal range, changes in the volume (and weight) of the perfusate do not significantly stiffen the parenchyma. Furthermore, Ptp-VL data obtained between 16 degrees C and 40 degrees C were superimposable, indicating that parenchymal mechanical properties evaluated at room temperature are valid at body temperature. Finally, the common assumptions of uniform deflation, homogeneity, and isotropy of bulk lung tissue appear consistent with the relationship between surface displacement and volume changes.

Adrenalectomy and surfactant in adult rats.

We examined the effect of adrenalectomy (ADX) on aspects of the surfactant system of adult rats. Five days after bilateral ADX, ADX rats had about 20% less disaturated phosphatidylcholine (DSPC) in lung lavage returns (airway DSPC) than sham-operated rats, but the amount of tissue DSPC was not different between the groups; airway DSPC formed 12.8 +/- 0.5% of total DSPC (airway + tissue) in ADX and 15.9 +/- 0.7% in sham-ADX rats. An ultrastructural morphometric analysis of alveolar type 2 cells did not reveal an effect of ADX on lamellar body volume density or surface-to-volume ratio. ADX rats had heavier lungs (not as a result of edema) than sham-ADX rats. Treatment of ADX rats with hydrocortisone returned the amount of DSPC toward normal and eliminated the increase of lung weight. ADX did not alter the recoil of saline-filled lungs but did slightly increase the recoil of air-filled lungs. We conclude that corticosteroid hormones influence the in vivo functioning of the surfactant system of adult rats, but this effect seems to be slight.

Protein Deficiency: Effects on Lung Mechanics and the Accumulation of Collagen and Elastin in Rat Lung

Groups of weanling (approximately 50 g) or young adult (approximately 300 g) rats were fed ad libitum casein-based diets varying in protein content from 4 to 16%. A group was also fed the 16% protein diet in an amout on a daily basis restricted to that consumed by the protein-deficient group (4% protein). The rats were fed the diets for either 4 weeks (weanling) or 6 weeks (adults). Protein-deficient or “food-restricted” rats (whether weanling or adults) were smaller and had smaller lungs than rats fed ad libitum the diets containing 16% protein. The lung elastin content was more resistant to dietary manipulation than was the lung collagen content. Lung collagen was significantly decreased in both weanling and adult rats fed the 4% protein diet. In weanling rats, pressure-volume relationships derived from saline-filled lungs (analyzed by exponential curve-fitting methods) suggested that lungs from food-restricted rats may be less compliant than lungs from rats fed the control diet ad libitum. When expressed in absolute terms, lungs from protein-deficient rats also appeared to be less compliant than normal rats; however, on a relative basis (percentage of volume at a given recoil pressure or the expression of volume on a weight basis) differences in compliance were less apparent. It is proposed that in weanling rats the differences in lung composition and compliance are the result of retarded lung growth and perhaps development.

Surface tension-surface area curves calculated from pressure-volume loops.

An energy analysis and data from the literature on the relation among surface area, recoil pressure, and lung volume are used to calculate the surface tension-surface area curves corresponding to pressure-volume loops. The energy analysis has been described earlier (J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 50: 921-926, 1981). It is based on the assumption that the tissue structure of the lung constitutes a conservative mechanical system and hence that pressure-volume hysteresis is primarily a result of surface tension-surface area hysteresis. Unlike previous methods of calculating surface tension from recoil pressure, this method does not rely on the assumption that the tissue component of recoil in the air-filled lung is the same as recoil pressure of the saline-filled lung at the same lung volume. The calculated values of surface tension decrease to less than 2 dyn/cm as surface area decreases along the deflation limb of the pressure-volume curve. Surface tension increases very steeply with surface area on the inflation limbs, reaching a limiting value of just under 30 dyn/cm. The shape of the surface tension-surface area curves, unlike the shape of the curves calculated by previous methods, is similar to the shape obtained on surface tension balances for fluid extracted from lungs.

Determinants of mechanical properties of rat lung during postnatal development.

We studied the volume-pressure curve of saline-filled lungs in rats between 4 and 40 days of age and correlated measurements of lung mechanical properties derived from these curves, e.g., lung volume at 10 cmH2O (V10), lung elastic recoil, the pressure required to rupture the lung (PRP), and hysteresis ratio (HR) with total lung collagen and elastin. Postnatal lung growth in the rat can be divided into four stages: lung expansion (between birth and 4 days); alveolar proliferation (between 4 and 12 days); elastin accumulation (between 12 and 20 days); and equilibrated growth (between 20 and 40 days). During lung expansion the lung contains little collagen or elastin, has small volumes, low elastic recoil, low PRP, and high HR. During alveolar proliferation lung volumes increase and HR falls, but elastic recoil and PRP do not change. During elastin accumulation lung elastin increases 297% and elastin concentration increases 261%, elastic recoil more than doubles reaching adult levels, and stress relaxation reaches adult values. During equilibrated growth lung elastin and V10/g lung weight plateau, but lung collagen increases 34.3% and collagen concentration doubles as does the structural integrity of the lung as measured by PRP. These studies illustrate the distinct effects of collagen and elastin on lung mechanical properties and define the mechanical consequences of the structural events associated with postnatal lung growth.

Peribronchial stress analysis utilizing concentric cylindrical shells of parenchyma.

The mechanical dependence of bronchial volume on parenchymal properties and on intrabronchial and pleural pressures was investigated utilizing finite elasticity theory. Treating the lung parenchyma as a compressible continuum, and using a simple strain-energy-density function fitted to pressure-volume curves of saline-filled lungs, we analyzed nonhomogeneous large deformations of the fluid-filled excised dog lobe by numerical procedures. For the purpose of obtaining peribronchial stress distributions, the lung was represented by a hollow very thick-walled cylinder corresponding to an axial bronchus with surrounding parenchyma. Finite elements consisted of concentric cylindrical shells. In general, we found that the theoretical results corresponded well to published stress and strain data for bronchial collapse. Peribronchial radial and circumferential stresses were found to be concentrated at the bronchial wall, but dissipated rapidly with 1-2 bronchial radii away from the wall. We conclude that the magnitude of regional lung recoil around bronchi during collapse can be reasonably well estimated by a theoretical analysis based on total lung pressure-volume relationships.

Role of surface tension and tissue in rat lung stress relaxation

When the volume of the lung is maintained constant after an initial change of volume, stress relaxation (SR) occurs as a slow decay of transpulmonary pressure (P TP). In order to define which structure in the lung is responsible for SR a multiple exponential fitting of the P TP variation has been made. Exercised rat lungs were placed in a fluid-filled box with trachea connected to atmosphere and submitted to stepwise changes of volume. Single volume steps (0.2 ml) were performed for lungs filled with either air or saline and the variations of P TP were monitored until steady state was reached. An exponential model (time constant = 6.5 ± 0.4 (SD) and 92 ± 6 s) described adequately the SR for air-filled lungs (n = 6) whereas only one exponential ( time constant = 6.7 ± 1.3 s) was required for saline-filled lungs. Multiple volume step experiments were also performed in air-filled lungs to obtain pressure volume loops. These hysteresis loops have been adequately simulated by use of the exponential model. It can be concluded that (1) lung tissue and air-liquid interface are both responsible for the SR, with, respectively, short and long time constants and (2) the same relaxation function is able to describe both stress relaxation and static hysteresis in such experimental conditions.

A model for mechanical structure of the alveolar duct.

The appearance of the microstructure of the lung as revealed in transmission and scanning electron micrographs of perfusion-fixed air- and saline-filled lungs suggests the following model for the structure of the alveolar duct. There are two networks of force-bearing elements. The first is an interdependent part of the peripheral connective tissue system that starts from the pleura and extends into the interlobar and interlobular fissures. At the sublobular level, its geometry is not yet fully clear. This network is extended by changes in lung volume and is insensitive to surface tension. The second network is composed of the line elements that form the rims of the alveolar openings. This network is the terminal part of the axial fiber system that surrounds bronchi, bronchioli, and arteries. The line elements of this network are extended by the outward force of surface tension. The two-dimensional alveolar walls that form the alveoli are negligible mechanical components except as platforms for surface tension at the air-liquid interface. An analysis of the mechanics of this model yields relations among surface area, recoil pressure, lung volume, and surface tension that are consistent with published data for lung volumes below 80% of total lung capacity.

Beta-Aminopropionitrile prevents bleomycin-induced pulmonary fibrosis in the hamster.

beta-Aminopropionitrile (beta APN), an agent that prevents collagen accumulation in tissues, was evaluated for its ability to prevent excess collagen formation in bleomycin-induced pulmonary fibrosis in the hamster. Two groups of animals received a single endotracheal dose of bleomycin; one of these was injected with beta APN twice daily for 30 days. A third group received endotracheal saline and a fourth group received saline and beta APN. After 30 days, we measured pressure-volume curves of saline-filled lungs, collagen content, and degree of fibrosis. Endotracheal bleomycin increased collagen content, decreased lung volume, and produced fibrosis and a mortality rate of 51%. The administration of beta APN to bleomycin-treated animals prevented excess collagen accumulation and diminished total protein, reversed volume diminution, produced less fibrosis, and improved the mortality rate to 24%; beta APN alone had no effect on lung mechanics or collagen content. The biochemical, functional, and structural features of bleomycin-induced lung fibrosis are amenable to control with beta APN.

Emphysema-like changes in the lungs of starved rats.

We examined the effects of starvation on lung structure in rats allowed only one fifth of their measured daily food consumption until they lost 40% of their initial body weight, and evaluated volume-pressure relationships in saline-filled lungs, lung morphometric and connective tissue morphologic features and lung ultrastructure by scanning electron microscopy. Compared with rats fed full rations, the volume-pressure curve was shifted upward and to the left and the chord compliance was significantly increased. In the starved rats, enlargement of air spaces and alveolar wall destruction was associated with a significant increase in mean linear intercept and a decrease in internal surface area. Elastic fibers appeared short, irregular, and fewer in number in starved lungs. Scanning electron microscopy showed enlarged air spaces, thin, irregular, and effaced alveolar walls, and an increased number and size of interalveolar pores in the starved group. We concluded that starvation results in mechanical and morphologic changes in the lung similar to those seen in emphysema, and that starved lung may be a useful experimental model for the study of emphysema.

Relations among recoil pressure, surface area, and surface tension in the lung.

The difference between energy stored in air- and saline-filled lungs is the sum of surface energy and the energy of tissue distortion caused by surface tension. The surface energy is zeta gamma dS, where gamma is surface tension and S is surface area. There is no corresponding relation between tissue energy and measurable variables. However, two equations can be obtained from the expression for the total energy difference. One is the statement that the total energy of the lung is minimum at equilibrium, and the other is the statement of conservation of mechanical energy as lung volume changes. The expression for tissue energy is eliminated between the two equations to obtain a single relation among the variables of interest: recoil pressure, surface area, and surface tension. Published data on recoil pressure and surface area of saline-filled, air-filled, and detergent-washed rabbit lungs are used in these equations to determine surface tension as a function of lung volume. The values of surface tension deduced from this analysis are lower than the values that would be obtained if the additional tissue forces in the air-filled lung were neglected. The contribution of tissue forces to the added recoil of the air-filled lung increases with increasing lung volume and accounts for approximately half the additional recoil at high lung volume.

The effects of desiccated thyroid on the rat lung.

Pressure-volume characteristics of whole lungs were measured in euthyroid rats and in rats fed 0.4% desiccated thyroid for eight weeks. The lungs were degassed by incising the diaphragm after the animals had breathed 100% oxygen for ten minutes. The pressure-volume characteristics were measured by inflating and deflating the lungs at a rate of 3.5 cc/min. Total lung capacity (TLC) was considered to be that volume of air required to produce a transpulmonary pressure of 30 cm H2O. At TLC there was 35% greater lung volume in the thyroid-treated animals than in their littermate controls. Similar results were observed in saline-filled lungs. Alveolar surface are (Sa) increased from 0.28m2 in the lungs of control animals to 0.75m2 in lungs of thyroid-treated animals. There was an 85% increase in the alveolar surface density (SVa) in the thyroid-treated animals. These results, obtained by morphometric analysis, suggest that greater lung volume in the thyroid-treated animals resulted from alveolar hyperplasia or "partitioning."

Influence of starvation on enzyme-induced emphysema.

Adult rats were exposed to an aerosol of 10% papain for 8 h twice in a 2-wk interval. The control rats were exposed to isotonic saline in the same manner. Three weeks after the final exposure rats were divided into four groups: emphysema-fed, emphysema-starved, control-fed, and control-starved. Starved animals received one-third of their measured daily food consumption and water ad libitum for 6 wk. Final body weight, dry and wet weights of lungs and postfixation lung volume (VL) were significantly lower in starved rats. Dry-to-wet weight ratios were not significantly different among the groups, but VL/body weight was significantly higher in starved animals. Elastic recoil pressure of lung tissue determined in saline-filled lungs decreased and chord compliance over mid- and high-volume ranges increased significantly in starved animals both in control and emphysema groups. Mean linear intercept of air spaces was greater and internal surface area was smaller in starved rats in each group. Therefore, it appears that starvation aggravates the preexisting emphysematous processes in rat lungs.

Pulmonary alveolar epithelial permeability in surgically induced hemorrhagic pancreatitis in dogs.

The adult respiratory distress syndrome has been associated with acute pancreatitis in 5-8% of patients. to determine, in a quantitative manner, the effects of acute, hemorrhagic pancreatitis on alveolar epithelial permeability, we studied two groups of dogs (group 1 - sham-operated, 7 dogs; group 2 - surgically induced pancreatitis, 7 dogs) and measured the flux of 10,000-20,000 molecular weight dextran and albumin (69,000 molecular weight), from the blood to the saline-filled lung. Following the surgical procedure (day 1), serum amylase levels increased significantly (397 +/- 70-1,268 +/- 95 dye units) in group 2 but not in group 1. Alveolar epithelial permeability (expressed as T1/2 time in minutes to 50% equilibration between blood and lung liquid) did not increase in either group for dextrans or albumin. We conclude that experimental acute pancreatitis does not cause an increase in alveolar epithelial permeability for molecular weight substances up to 69,000 daltons.

Alveolar volume-surface area relation in air- and saline-filled lungs fixed by vascular perfusion.

The influence of volume changes and interfacial forces on the geometry of peripheral air spaces was studied in excised rabbit lungs inflated with either air or saline and fixed by vascular perfusion at four points of the deflation limb of the pressure-volume curve corresponding to 100, 80, 60, and 40% of the total lung capacity (TLC). In air-filled lungs pleating and folding of alveolar septa were observed, especially in alveolar corners. However, the alveolar surfaces were smooth, except at low lung volumes where some surface crumpling occurred. In saline-filled lungs pleats were absent; the alveolar surface was irregular at all inflation levels due to undulating walls and bulging capillaries. Morphometry indicated that at all alveolar volumes (VA) the surface areas (SA) were larger in saline- than air-filled lungs. No simple mathematical function was found to characterize the relation between SA and VA over the entire volume range studied. Within the range of normal breaths (80 to 40% TLC) the best fit for n in the function SA = k.VnA was 0.58 for saline-filled lungs (r = 0.93) and 0.33 for air-filled lungs (r = 0.68), suggesting different and complex deflation patterns.

Effect of lung surface tension on bronchial collapsibility in excised dog lungs.

Bronchial collapsibilities were studied in air- and saline-filled excised dog lungs. The intrapulmonary bronchi were isolated from the rest of the lung parenchyma with beads placed at their tributary bronchi as described previously by Takishima et al. (J. Appl. Physiol. 38: 875-881, 1975). Pressure-volume relations of the isolated bronchi were obtained while lung volume (VL) was kept constant. When lung recoil pressure (PL) was reduced by filling the lung with saline at a given VL, bronchial areas were smaller and bronchial collapsibilities were larger than in the air-filled lung. When bronchial areas and bronchial collapsibilities in air- and saline-filled lungs were compared at a given PL, they were approximately identical. We concluded that bronchial areas and collapsibilities were primarily determined by PL rather than VL, and lung surface tension itself made bronchial collapsibility equal to or even less than the degree of collapsibility due to forces applied from surrounding lung tissues that distended the bronchi.

The effects of endogenous and exogenous histamine on pulmonary alveolar membrane permeability.

The effects of exogenously administered histamine phosphate (0.1 microgram per kg of body weight per min, or 90 microgram per hour) and endogenous histamine released by intravenous injection of 0.5 mg of Compound 48/80 on alveolar membrane permeability to substances of differing molecular weight (60 to 20,000 daltons) were studied using the in vivo saline-filled dog lung model. The half-time, i.e., the time required for 50 per cent equilibration between tracer substances in the blood compared to the saline-filled lung, was measured at baseline for urea, sucrose, and dextrans of varying molecular weight. The half-time decreased significantly for substances as large as 10,000 daltons after histamine infusion, and 20,000 daltons after injection of Compound 48/80. We conclude that histamine can increase alveolar epithelial permeability for substances of low molecular weight.

Lung mechanics and ultrastructure in prolonged starvation.

This study was designed to examine the influence of prolonged caloric deprivation on the mechanical and ultrastructural characteristics of rat lungs. We measured the static deflation pressure-volume relationships in air- and saline-filled lungs and we used morphometric techniques to analyze the cytoplasmic components of pulmonary granular pneumocytes. Adult rats were allowed one fifth of their usual daily food consumption and water ad libitum for 3 weeks. Body weights and wet and dry weights of lung were significantly decreased in starved rats with no significant differences in lung dry-to-wet weight ratios compared to the control animals. In starved rats, pressure-volume curves of air-filled lungs, expressed as a percentage of maximal lung volume were significantly shifted downward and to the right, indicating a significant increase in surface forces, whereas saline pressure-volume curves, as a percentage of maximal lung volume, were shifted upward and to the left, indicating a significant decrease in ti...

Exercise stress and enzyme-induced emphysema.

Rats were exposed to an aerosol of 10% papain for 8 h found in pilot studies to produce marked emphysema. One week after exposure some animals were forced to exercise in a motor-driven activity wheel 2 h daily for 4 wk, while others remained at rest. Another group of rats which served as the control were exposed to saline under the same conditions and divided into exercise and rest groups. Elastic recoil pressure (Pst) of lung was measured from static deflation pressure-volume curves with air and saline. Pst measured in air-filled lungs was not significantly different between the emphysema-rest and emphysema-exercise groups. When inflated with saline the Pst was significantly reduced in the emphysema-exercise compared to the emphysema-rest group at high and mid (100, 80, 60%) lung volumes. Pst in air- and saline-filled lungs was not significantly different between the control-rest and control-exercise groups. We therefore conclude that mechanical stress resulting from physical exercise decreased Pst of lung tissue in emphysematous rats.