Absolute lung volumes such as functional residual capacity, residual volume (RV), and total lung capacity (TLC) are used to characterize emphysema in patients, whereas in animal models of emphysema, the mechanical parameters are invariably obtained as a function of transrespiratory pressure (Prs). The aim of the present study was to establish a link between the mechanical parameters including tissue elastance (H) and airway resistance (Raw), and thoracic gas volume (TGV) in addition to Prs in a mouse model of emphysema. Using low-frequency forced oscillations during slow deep inflation, we tracked H and Raw as functions of TGV and Prs in normal mice and mice treated with porcine pancreatic elastase. The presence of emphysema was confirmed by morphometric analysis of histological slices. The treatment resulted in an increase in TGV by 51 and 44% and a decrease in H by 57 and 27%, respectively, at 0 and 20 cmH(2)O of Prs. The Raw did not differ between the groups at any value of Prs, but it was significantly higher in the treated mice at comparable TGV values. In further groups of mice, tracheal sounds were recorded during inflations from RV to TLC. All lung volumes but RV were significantly elevated in the treated mice, whereas the numbers and size distributions of inspiratory crackles were not different, suggesting that the airways were not affected by the elastase treatment. These findings emphasize the importance of absolute lung volumes and indicate that tissue destruction was not associated with airway dysfunction in this mouse model of emphysema.

During slow inflation of lung lobes, we measure a sequence of short explosive transient sound waves called "crackles," each consisting of an initial spike followed by ringing. The crackle time series is irregular and intermittent, with the number of spikes of size s following a power law, n(s) proportional, variants(-alpha), with alpha=2.77+/-0.05. We develop a model of crackle wave generation and propagation in a tree structure that combines the avalanchelike opening of airway segments with the wave propagation of crackles in a tree structure. The agreement between experiments and simulations suggests that (i) the irregularities are a consequence of structural heterogeneity in the lung, (ii) the intermittent behavior is due to the avalanchelike opening, and (iii) the scaling is a result of successive attenuations acting on the sound spikes as they propagate through a cascade of bifurcations along the airway tree.

The mechanics of the regional airways and tissues was studied in isolated dog lobes by means of a modified wave-tube technique. Small-amplitude pseudorandom forced oscillations between 0.1 and 48 Hz were applied through catheters wedged in 2-mm-diameter bronchi in three regions of each lobe at translobar pressures (PL) of 10, 7, 5, 3, 2, and 1 cmH2O. The measured regional input impedances were fitted by a model containing the resistance (R1) and inertance (I) of the regular (segmental) airways, the resistance of the collateral channels (R2), and the damping (G) and elastance (H) of the local tissues. This model gave far better fits to the data on impedance of the lung periphery than when G and H were replaced by a single tissue compliance, which explains why interruption of segmental flow did not lead to monoexponential pressure decay in previous studies. The interlobar and intralobar variances of the parameters were equally significant, and poor correlations were found between the airway parameters R1 and R2 and between any airway and tissue parameter (e.g., R1 and H). R2 was on average approximately 10 times higher than R1, although the R2-to-R1 ratios and their dependencies on PL were regionally highly variable. However, for the total of 33 regions studied, the PL dependence was the same for R1 and R2, which may reflect similar morphological structures for the regular and collateral airways. The dependencies of G and H on PL showed high interregional variations; generally, however, they assumed their minima at medium PL values (approximately 5 cmH2O).

In 11 isolated dog lung lobes, we studied the size distribution of recruited alveolar volumes that become available for gas exchange during inflation from the collapsed state. Three catheters were wedged into 2-mm-diameter airways at total lung capacity. Small-amplitude pseudorandom pressure oscillations between 1 and 47 Hz were led into the catheters, and the input impedances of the regions subtended by the catheters were continuously recorded using a wave tube technique during inflation from -5 cm H(2)O transpulmonary pressure to total lung capacity. The impedance data were fit with a model to obtain regional tissue elastance (Eti) as a function of inflation. First, Eti was high and decreased in discrete jumps as more groups of alveoli were recruited. By assuming that the number of opened alveoli is inversely proportional to Eti, we calculated from the jumps in Eti the distribution of the discrete increments in the number of opened alveoli. This distribution was in good agreement with model simulations in which airways open in cascade or avalanches. Implications for mechanical ventilation may be found in these results.

The aim of this study was to test the hypothesis that the mechanism of recruitment and the lower knee of the pressure-volume curve in the normal lung are primarily determined by airway reopenings via avalanches rather than simple alveolar recruitments. In isolated dog lung lobes, the pressure-volume loops were measured, and crackle sounds were recorded intrabronchially during both the first inflation from the collapsed state to total lobe capacity and a second inflation without prior degassing. The inflation flow contained transients that were accompanied by a series of crackles. Discrete volume increments were estimated from the flow transients, and the energy levels of the corresponding crackles were calculated from the sound recordings. Crackles were concentrated in the early phase of inflation, with the cumulative energy exceeding 90% of its final value by the lower knee of the pressure-volume curve. The values of volume increments were correlated with crackle energy during the flow transient for both the first and the second inflations (r(2) = 0.29-0.73 and 0.68-0.82, respectively). Because the distribution of volume increments followed a power law, the correlation between crackle energy and discrete volume increments suggests that an avalanche-like airway opening process governs the recruitment of collapsed normal lungs.