A model of the recruitment-derecruitment and volume of lung units in an excised lung as it is inflated-deflated between minimum and maximum lung volume.

The role of the recruitment-derecruitment of small structures in the lung (lung units) as the lung increases and decreases in volume has been debated. The objective of this study was to develop a model to estimate the change in the number and volume of open lung units as an excised lung is inflated-deflated between minimum and maximum lung volume. The model was formulated based on the observation that the compliance of the slowly changing quasi-static pressure-volume (P-V) curve of an excised rat lung can differ from the compliance of a faster changing small sinusoidal pressure volume perturbations superimposed on the curve. In those regions of the curve where differences in compliance occur, the lung tissue properties exhibit nonlinear characteristics, which cannot be linearized using "incremental" or "small signal" analysis. The model attributes the differences between the perturbation and quasi-static compliance to an additional nonlinear compliance term that results from the sequential opening and closing of lung units. Using this approach, it was possible to calculate the normalized average volume and the normalized number of open units as the lung is slowly inflated-deflated. Results indicate that the normalized average volume and the normalized number of open units are not linearly related to normalized lung volume, and at equal lung volumes the normalized number of open units is greater and the normalized average lung unit volume is smaller during lung deflation when compared to lung inflation. In summary, a model was developed to describe the recruitment-derecruitment process in excised lungs based on the differences between small signal perturbation compliance and quasi-static compliance. Values of normalized lung unit volume and the normalized number of open lung units were shown to be nonlinear functions of both transpulmonary pressure and normalized lung volume.

Lung area--volume models in relation to the recruitment--derecruitment of individual lung units.

The objective of this study was to reconsider some of the previous experimental results in terms of simple geometric models in order to determine if any of the apparent conflicts could be explained within a more unified concept. These models allow individual lung units and the entire lung to expand differently with regard to their area-volume relationship. The effect of a recruitment-derecruitment process as the lung inflates-deflates is also considered. Examples are used to illustrate how some of the apparent conflicts found in the literature may arise from whether or not recruitment and derecruitment take place during lung expansion and contraction.

Discountinuous lung sounds and hysteresis in control and Tween 20-rinsed excised rat lungs.

In the past, the relationship between pulmonary hysteresis and a model of the recruitment-derecruitment of lung units has been explored (Cheng, W., DeLong, D.S., Franz, G.N., Petsonk, E.L., Frazer, D.G., 1995, Resp. Physiol. 102, 205-215). The recruitment process is characterized by a sequence of events which represents discrete configurational changes in lung structure. It is assumed that energy released during the opening of lung units is associated with the formation of discontinuous lung sounds. The goal of this study was to record tracheal sounds for lungs inflated from different end-expiratory pressures and to relate the sound power to the normalized hysteresis of individual pressure-volume (PL-VL) loops. PL-VL curves and lung sounds were recorded for control lungs and lungs rinsed with Tween 20 in order to estimate the role of alveolar surfactant on the recruitment-derecruitment process. Results indicate that there may be two populations of lung units, one which is altered by Tween 20 and another which is not. The population not affected by Tween 20 appears to be responsible for producing discrete lung sounds and may represent the opening of larger conducting airways. The second population, possibly within the respiratory zone, is affected by alterations in surface tension and contributes to pulmonary hysteresis, but, apparently, does not contribute significantly to lung sound power measured at the trachea.

Contribution of opening and closing of lung units to lung hysteresis.

The recruitment and derecruitment of lung units is one explanation of the hysteresis observed in an excised lung during inflation and deflation. A simplified model has been proposed in which the recruitment-derecruitment process is a function of end-expiratory pressure (Frazer, D.G., K.C. Weber and G.N. Franz, Respir. Physiol. 61: 277-288, 1985). The object of this study was to test this model with three experimental procedures. During the first set of experiments, progressively larger pressure-volume (PL-VL) loops were recorded with end-expiratory pressure held at either -5 cmH2O, where all lung units are assumed to be closed, or +5 cmH2O, where all recruited lung units are assumed to be open. In the first case hysteresis is maximal, in the second, minimal. The difference in hysteresis is presumed to arise from the recruitment-derecruitment process. In the second set of experiments, excised lungs are slowly inflated and then deflated at a constant rate while constant-amplitude sinusoidal volume oscillations are superimposed. The end-expiratory pressure of the superimposed loops gradually rose as the lung was inflated and fell as the lung was deflated. Hysteresis was minimal when end-expiratory pressure was above 4 +/- 1 cmH2O even as peak-to-peak loop pressure greatly varied. This supports the notion of an end-expiratory pressure dependent mechanism of recruitment/derecruitment. During the third set of experiments lungs were inflated to either 50%, 75%, or 100% TLC. Volumes of air were then withdrawn and replaced so that the initial volume was restored in sinusoidal fashion as the amplitude of the volume excursions increased. For PL-VL loops with end-expiratory pressures between +4 and -2 cmH2O, pressure amplitudes rose and the hysteresis index (loop area/tidal volume) increased, regardless of the initial lung volume. These results are consistent with the previously described model of Frazer et al. (1985) which assumed that PL-VL curves can be divided into an 'opening' region, an 'open' region and a 'closing' region and that the demarcation of these regions depends on transpulmonary pressure, specifically end-expiratory pressure, and to a much lesser degree on lung volume.

Evidence of sequential opening and closing of lung units during inflation-deflation of excised rat lungs.

In this study we propose a descriptive model of the events occurring in an excised lung during an inflation-deflation cycle. The model was developed by observing changes in small pressure-volume loops superimposed on quasistatic pressure volume curves. It was found that the shape of the small loops during lung inflation was a function of the previous end-expiratory pressure. These experimental results could most easily be explained by a model of the lung in which individual lung units open sequentially as the lung is inflated. During sequential recruitment, individual lung units open quickly to a volume determined by the transpulmonary pressure. The units then homogeneously increase and decrease in size according to pressure-volume curves similar to the deflation curve of the entire lung. Once lung units have been recruited, they remain open until the lung has been deflated to end-expiratory pressures below 3-4 cm H2O. Reducing the end-expiratory pressure to lower values causes additional derecruitment of lung units until a transpulmonary pressure of 0.0 to -1.0 cm H2O has been reached.

Microcinematographic analysis of tethered Leptospira illini.

A model of Leptospira motility was recently proposed. One element of the model states that in translating cells the anterior spiral-shaped end gyrates counterclockwise and the posterior hook-shaped end gyrates clockwise. We tested these predictions by analyzing cells tethered to a glass surface. Leptospira illini was incubated with antibody-coated latex beads (Ab-beads). These beads adhered to the cells, and subsequently some cells became attached to either the slide or the cover glass via the Ab-beads. As previously reported, these cells rapidly moved back and forth across the surface of the beads. In addition, a general trend was observed: cells tethered to the cover glass rotated clockwise around the Ab-bead; cells tethered to the slide rotated counterclockwise around the Ab-bead. A computer-aided microcinematographic analysis of tethered cells indicated that the direction of rotation of cells around the Ab-bead was a function of both the surface of attachment and the shape of the cell ends. The results can best be explained by assuming that the gyrating ends interact with the glass surface to cause rotation around the Ab-beads. The analysis obtained indicates that the hook- and spiral-shaped ends rotate in the directions predicted by the model. In addition, the tethered cell assay permitted detection of rapid, coordinated reversals of the cell ends, e.g., cells rapidly switched from a hook-spiral configuration to a spiral-hook configuration. These results suggest the existance of a mechanism which coordinates the shape of the cell ends of L. illini.

Regional differences in gas trapping (airway closure) between apex and base of excised rat lungs.

Excised rat lungs were ventilated with air under three conditions: (a) while suspended by the trachea and surrounded by air, (b) while inverted and surrounded by saline, and (c) while upright and surrounded by saline. The distribution of transpulmonary pressures over which gas trapping occurred in the lung for each of the three conditions was found by a method previously described by Frazer et al. (1979). A distribution having a small standard deviation (SD) indicates more uniform gas trapping in the lung while a larger SD indicates less uniform gas trapping. Results showed that the SD was 0.63 for the inverted lung in saline, 1.10 for the lung in air, and 1.57 for the upright lung in saline. We conclude that gas trapping in lungs inverted in saline occurs more uniformly than gas trapping in lungs in air or upright in saline. The results obtained in saline in the upright and inverted position also imply that as the lung is deflated surrounded by air, gas trapping initially occurs in the base of the lung before it occurs in the apex. Since gas trapping and airway closure are related, there could also be intrinsic dissimilarities in airway closure between the apex and base of excised rat lungs suspended by the trachea in air.

The effect of temperature on gas trapping in excised lungs.

In this study the effect of temperature on gas trapping in excised lungs was examined with two types of experiments in rats. In the first, changes in gas trapping following ten successive inflation-deflation cycles at the same constant ventilation rate were examined at 17, 27, 37 and 42 degrees C. In the second, the effects of five different ventilation rates at temperatures of 17, 27 and 37 degrees C were determined. The fraction of gas trapped in lungs repeatedly ventilated for ten inflation-deflation cycles at constant ventilation rates remained nearly constant with time at 17 and 27 degrees C but decreased with time at 37 and 42 degrees C. The amount of gas trapped in the lung at 27 degrees C fell with the logarithm of increasing ventilation rate. Lowering the temperature shifted this relationship toward lower ventilation rates while increasing the temperatures caused an apparent shift toward higher ventilation rates.

Trapped gas and lung hysteresis.

The amount of gas trapped in excised rat lungs was determined after four inflation-deflation cycles between total lung capacity (TLC) and several end-expiratory volumes or end-expiratory pressures. Lungs ventilated in this way exhibited pressure-volume curves that formed closed loops with varying degrees of hysteresis. The area of these loops was highly correlated with the amount of gas trapped in the lungs. Trapped gas volume and hysteresis increased with deflation to increasingly lower end-expiratory volumes or pressures. The processes responsible for lung hysteresis, however, seem to be primarily dependent upon end-expiratory pressure and only slightly dependent upon end-expiratory volume. A possible explanation of these findings is that menisci, formed in the small airways of the lung during deflation at low lung volumes, are responsible for both the trapped gas and the pressure-volume hysteresis of the lung.