Effect of surface tension on alveolar surface area.

At fixed lung volume (VL), alterations in surface tension change alveolar surface area (S) and lung recoil (PL). Wilson (26), using data from fixed lungs (1, 9), quantified the isovolume change in S with PL. We reexamined this question in fresh excised rabbit lungs, with two important differences. First, we measured fractional changes in S by using diffuse light scattering, avoiding the potential upset of the balance of tissue and surface forces during fixation. Second, we altered surface tension by ventilating the lungs with nebulized polydimethylsiloxane, with much less residual fluid compared with lavage. We found that S decreased at low and mid VL (treatment surface tension > control) by about half of Wilson's estimates and was nearly unaffected by treatment at high VL. This suggests that with increased surface tension there is 1) greater septal retraction in lungs fixed by vascular perfusion compared with unfixed lungs and 2) a greater increase in PL and less loss of S than would have been predicted.     

Relations among alveolar surface tension, surface area, volume, and recoil pressure

For pulmonary structure-function analysis excised rabbit lungs were fixed by vascular perfusion at six points on the pressure-volume (P-V) curve, i.e. at 40, 80, and 100% of total lung capacity (TLC) on inflation, at 80 and 40% TLC on deflation, and at 80% TLC on reinflation. Before fixation alveolar surface tensions (gamma) were measured in individual alveoli over the entire P-V loop, using an improved microdroplet method. A maximal gamma of approximately 30 mN/m was measured at TLC, which decreased during lung deflation to about 1 mN/m at 40% TLC. Surface tensions were considerably higher on the inflation limb starting from zero pressure than on the deflation limb (gamma-V hysteresis). In contrast, the corresponding alveolar surface area-volume (SA-V) relationship did not form a complete hysteresis over the entire volume range. There was a considerable difference in SA between lungs inflated to 40% TLC (1.49 +/- 0.11 m2) and lungs deflated to 40% TLC (2.19 +/- 0.21 m2), but at 80% TLC the values of SA were essentially the same regardless of the volume history. The data indicate that the gamma-SA hysteresis is only in part accountable for the P-V hysteresis and that the determinative factors of alveolar geometry change with lung volume. At low lung volumes airspace dimensions appear to be governed by an interplay between surface and tissue forces. At higher lung volumes the tissue forces become predominant.     

Effects of lung volume and alveolar surface tension on pulmonary vascular resistance

Utilizing the arterial and venous occlusion technique, the effects of lung inflation and deflation on the resistance of alveolar and extraalveolar vessels were measured in the dog in an isolated left lower lobe preparation. The lobe was inflated and deflated slowly (45 s) at constant speed. Two volumes at equal alveolar pressure (Palv = 9.9 +/- 0.6 mmHg) and two pressures (13.8 +/- 0.8 mmHg, inflation; 4.8 +/- 0.5 mmHg, deflation) at equal volumes during inflation and deflation were studied. The total vascular pressure drop was divided into three segments: arterial (delta Pa), middle (delta Pm), and venous (delta Pv). During inflation and deflation the changes in pulmonary arterial pressure were primarily due to changes in the resistance of the alveolar vessels. At equal Palv (9.9 mmHg), delta Pm was 10.3 +/- 1.2 mmHg during deflation compared with 6.8 +/- 1.1 mmHg during inflation. At equal lung volume, delta Pm was 10.2 +/- 1.5 mmHg during inflation (Palv = 13.8 mmHg) and 5.0 +/- 0.7 mmHg during deflation (Palv = 4.8 mmHg). These measurements suggest that the alveolar pressure was transmitted more effectively to the alveolar vessels during deflation due to a lower alveolar surface tension. It was estimated that at midlung volume, the perimicrovascular pressure was 3.5-3.8 mmHg greater during deflation than during inflation.     

Effect of increased alveolar surface tension on segmental pulmonary vascular resistance

The site of change in pulmonary vascular resistance (PVR) after surfactant displacement with the detergent diocytl sodium sulfosuccinate (OT) was studied in the isolated canine left lower lobe preparation. Changes in PVR were assessed using the arterial and venous occlusion technique and the vascular pressure-flow relationship. Changes in alveolar surface tension were confirmed from measurements of pulmonary compliance as well as from measurements of surface tension of extracts from lung homogenates. After surfactant depletion (the perfusion rate constant) the total pressure gradient (delta PT) across the lobe increased from 13.4 +/- 1 to 17.1 +/- 0.8 mmHg. This increase in delta PT was associated with a significant increase in the arterial and venous gradients (3.7 +/- 0.3 to 4.9 +/- 0.4 and 5.7 +/- 0.5 to 9.4 +/- 0.6 mmHg, respectively) and a decrease in middle pressure gradient (4.1 +/- 0.8 to 2.9 +/- 0.6 mmHg). The vascular pressure-flow relationship supported these findings and showed that the mean slope increased by 52% (P less than 0.05), whereas the pressure intercept decreased slightly but not significantly (3.7 +/- 0.7 to 3.2 +/- 0.8 mmHg). These results suggest that the resistance of arteries and veins increases, whereas the resistance of the middle segment decreases after surfactant depletion. These effects were apparently due to surface tension that acts directly on the capillary wall. Direct visualization of subpleural capillaries supported the notion that capillaries become distended and recruited as alveolar surface tension increases. In the normal lung (perfused at constant-flow rate) changes in alveolar pressure (Palv) were transmitted fully to the capillaries as suggested by equal changes in pulmonary arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary surfactant in birds: coping with surface tension in a tubular lung

As birds have tubular lungs that do not contain alveoli, avian surfactant predominantly functions to maintain airflow in tubes rather than to prevent alveolar collapse. Consequently, we have evaluated structural, biochemical, and functional parameters of avian surfactant as a model for airway surfactant in the mammalian lung. Surfactant was isolated from duck, chicken, and pig lung lavage fluid by differential centrifugation. Electron microscopy revealed a uniform surfactant layer within the air capillaries of the bird lungs, and there was no tubular myelin in purified avian surfactants. Phosphatidylcholine molecular species of the various surfactants were measured by HPLC. Compared with pig surfactant, both bird surfactants were enriched in dipalmitoylphosphatidylcholine, the principle surface tension-lowering agent in surfactant, and depleted in palmitoylmyristoylphosphatidylcholine, the other disaturated phosphatidylcholine of mammalian surfactant. Surfactant protein (SP)-A was determined by immunoblot analysis, and SP-B and SP-C were determined by gel-filtration HPLC. Neither SP-A nor SP-C was detectable in either bird surfactant, but both preparations of surfactant contained SP-B. Surface tension function was determined using both the pulsating bubble surfactometer (PBS) and capillary surfactometer (CS). Under dynamic cycling conditions, where pig surfactant readily reached minimal surface tension values below 5 mN/m, neither avian surfactant reached values below 15 mN/m within 10 pulsations. However, maximal surface tension of avian surfactant was lower than that of porcine surfactant, and all surfactants were equally efficient in the CS. We conclude that a surfactant composed primarily of dipalmitoylphosphatidylcholine and SP-B is adequate to maintain patency of the air capillaries of the bird lung.     

Asymmetrical membranes and surface tension

The (31)P-nuclear magnetic resonance chemical shift of phosphatidic acid in a membrane is sensitive to the lipid head group packing and can report qualitatively on membrane lateral compression near the aqueous interface. We have used high-resolution (31)P-nuclear magnetic resonance to evaluate the lateral compression on each side of asymmetrical lipid vesicles. When monooleoylphosphatidylcholine was added to the external monolayer of sonicated vesicles containing dioleoylphosphatidylcholine and dioleoylphosphatidic acid, the variation of (31)P chemical shift of phosphatidic acid indicated a lateral compression in the external monolayer. Simultaneously, a slight dilation was observed in the inner monolayer. In large unilamellar vesicles on the other hand the lateral pressure increased in both monolayers after asymmetrical insertion of monooleoylphosphatidylcholine. This can be explained by assuming that when monooleoylphosphatidylcholine is added to large unilamellar vesicles, the membrane bends until the strain is the same in both monolayers. In the case of sonicated vesicles, a change of curvature is not possible, and therefore differential packing in the two layers remains. We infer that a variation of lipid asymmetry by generating a lateral strain in the membrane can be a physiological way of modulating the conformation of membrane proteins.     

Biofeedback of alveolar carbon dioxide tension and levels of arousal

This is a preliminary study designed to investigate the potential usefulness of alveolar (lung) CO₂ feedback training in promoting sleep onset in primary insomniacs. The present study was undertaken to determine if normal subjects could, without obvious manipulation of breathing, bring alveolar (lung) CO₂ tension under voluntary control using biofeedback techniques and, if so, whether this control would be accompanied by shifts in level of wakefulness. Subjects participated in five baseline and five training sessions in which EEG, alveolar CO₂ tension, and thoracic/abdominal respiratory movement were monitored. The feedback consisted of a pitch-modulated tone plus visual scores. We found that CO₂ tension in awake portions of up trials was significantly higher than for awake portions of down trials (p<.01), indicating that learning had occurred. In the initial trials, when subjects raised CO₂ tension they became drowsy and often fell asleep, and when they lowered CO₂ tension they aroused themselves. However, when subjects were awakened immediately upon falling asleep, there developed a decoupling of EEG and CO₂ changes. The presence of such a decoupling phenomenon makes it unclear whether CO₂ feedback will be useful in promoting sleep onset in primary insomniacs.This study was supported by National Institute of Mental Health Research Fellowship MH05151, Research Grant MH29369, Research Scientist Development Award MH38897, and by a Biomedical Research Support Grant to Langley Porter Institute, 507RR05755.     

Biofeedback of alveolar carbon dioxide tension and levels of arousal

This is a preliminary study designed to investigate the potential usefulness of alveolar (lung) CO2 feedback training in promoting sleep onset in primary insomniacs. The present study was undertaken to determine if normal subjects could, without obvious manipulation of breathing, bring alveolar (lung) CO2 tension under voluntary control using biofeedback techniques and, if so, whether this control would be accompanied by shifts in level of wakefulness. Subjects participated in five baseline and five training sessions in which EEG, alveolar CO2 tension, and thoracic/abdominal respiratory movement were monitored. The feedback consisted of a pitch-modulated tone plus visual scores. We found that CO2 tension in awake portions of "up" trials was significantly higher than for awake portions of "down" trials (p less than .01), indicating that learning had occurred. In the initial trials, when subjects raised CO2 tension they became drowsy and often fell asleep, and when they lowered CO2 tension they aroused themselves. However, when subjects were awakened immediately upon falling asleep, there developed a decoupling of EEG and CO2 changes. The presence of such a decoupling phenomenon makes it unclear whether CO2 feedback will be useful in promoting sleep onset in primary insomniacs.     

Surface tension influences cell shape and phagocytosis in alveolar macrophages

The effect of surface tension on alveolar macrophage shape and phagocytosis was assessed in vivo and in vitro. Surface tension was regulated in vivo by conditionally expressing surfactant protein (SP)-B in Sftpb-/- mice. Increased surface tension and respiratory distress were produced by depletion of SP-B and were readily reversed by repletion of SP-B in vivo. Electron microscopy was used to demonstrate that alveolar macrophages were usually located beneath the surfactant film on the alveolar surfaces. Reduction of SP-B increased surface tension and resulted in flattening of alveolar macrophages on epithelial surfaces in vivo. Phagocytosis of intratracheally injected fluorescent microbeads by alveolar macrophages was decreased during SP-B deficiency and was restored by repletion of SP-B in vivo. Incubation of MH-S cells, a mouse macrophage cell line, with inactive surfactant caused cell flattening and decreased phagocytosis in vitro, findings that were reversed by the addition of sheep surfactant or phospholipid containing SP-B. SP-B controls surface tension by forming a surfactant phospholipid film that regulates shape and nonspecific phagocytic activity of alveolar macrophages on the alveolar surface.     

Contributions to the mathematical theory of the stability of metabolizing systems with variable surface tension

The paper investigates the stability of a metabolizing system subject to surface tension forces only. In line with some earlier work of N. Rashevsky, the surface tension is considered as a function of the concentration of the metabolite. Different theoretically interesting cases are discussed. The study indicates that surface tension forces alone are not likely to produce phenomena similar to those of cell division.     

Cell membranes after malignant transformation. Part I: Dynamic stability at low surface tension

A hydrodynamic cell model is introduced to analyze the dynamic stability of the cell membrane after malignant transformation. The cell membrane is considered as a two-dimensional charged interface between intra- and extra-cellular fluids. Employing a first order stability analysis, conditions are established under which growth of surface fluctuations can occur (leading to microvilli formation or cell division). The system is unstable if the total surface tension, i.e. the pure surface tension plus the free energy of formation of the double layers, is negative. Following that criterion, cell division is promoted in cancer cells; moreover, as cancer cells are more fluid than normal cells, they will divide more rapidly. The model also predicts that microvilli (protrusions of the cell membrane) will have a diameter of the order of the dominant wavelengths of perturbation (0.1 - 1 mu) which supports the view that such protrusions are consequences of amplified cell surface fluctuations.