Recent studies have suggested that part of the measured increase in lung tissue resistance after bronchoconstriction is an artifact due to increased airway inhomogeneities. To resolve this issue, we measured lung impedance (ZL) in seven open-chest rats with the lungs equilibrated on room air and then on a mixture of neon and oxygen (NeOx). The rats were placed in a body box with the tracheal tube leading through the box wall. A broadband flow signal was delivered to the box. The signal contained seven oscillation frequencies in the 0.234- to 12.07-Hz range, which were combined to produce tidal ventilation. The ZL was measured before and after bronchoconstriction caused by infusion of methacholine (MCh). Partitioning of airway and tissue properties was achieved by fitting ZL with a model including airway resistance (Raw), airway inertance, tissue damping (G), and tissue elastance (H). We hypothesized that if the inhomogeneities were not significant, the apparent tissue properties would be independent of the resident gas, whereas Raw would scale as the ratio of viscosities. Indeed, during control conditions, the NeOx-to-air ratios for G and H were both 1.03 +/- 0.04. Also, there was a small increase in lung elastance (EL) between 0.234 and 4 Hz that was similar on air and NeOx. During MCh infusion, Raw and G increased markedly (45-65%), but the increase in H was relatively small ( < 13%). The NeOx-to-air Raw and H ratios remained the same. However, the NeOx-to-air G ratio increased to 1.19 +/- 0.07 (P < 0.01) and the increase in EL with frequency was now marked and dependent on the resident gas. These results provide direct evidence that for a healthy rat lung airway inhomogeneities do not significantly influence the lung resistance or EL vs. frequency data. However, during MCh-induced constriction, a large portion of the increase in tissue resistance and the altered frequency dependence of EL are virtual and a consequence of the augmented airway inhomogeneities.

To determine the predominant site of action of methacholine (MCh) on lung mechanics, two groups of open-chest Sprague-Dawley rats were studied. Five rats were measured during intravenous infusion of MCh (i.v. group), with doubling of concentrations from 1 to 16 micrograms.kg-1.min-1. Seven rats were measured after aerosol administration of MCh with doses doubled from 1 to 16 mg/ml (ae group). Pulmonary input impedance (ZL) between 0.5 and 21 Hz was determined by using a wave-tube technique. A model containing airway resistance (Raw) and inertance (Iaw) and parenchymal damping (G) and elastance (H) was fitted to the ZL spectra. In the iv group, MCh induced dose-dependent increases in Raw [peak response 270 +/- 9 (SE) % of the control level; P < 0.05] and in G (340 +/- 150%; P < 0.05), with no increase in Iaw (30 +/- 59%) or H (111 +/- 9%). In the ae group, the dose-dependent increases in Raw (191 +/- 14%; P < 0.05) and G (385 +/- 35%; P < 0.05) were associated with a significant increase in H (202 +/- 8%; P < 0.05). Measurements with different resident gases [air vs. neon-oxygen mixture, as suggested (K.R. Lutchen, Z. Hantos, F. Peták, A. Adamicza, and B. Suki J. Appl. Physiol. 80: 1841-1849, 1996)] in the control and constricted states in another group of rats suggested that the entire increase seen in G during the i.v. challenge was due to ventilation inhomogeneity, whereas the ae challenge might also have involved real tissue contractions via selective stimulation of the muscarinic receptors.

When lungs are emptied during exhalation, peripheral airways close up. For people with lung disease, they may not reopen for a significant portion of inhalation, impairing gas exchange. A knowledge of the mechanisms that govern reinflation of collapsed regions of lungs is therefore central to the development of ventilation strategies for combating respiratory problems. Here we report measurements of the terminal airway resistance, Rt, during the opening of isolated dog lungs. When inflated by a constant flow, Rt decreases in discrete jumps. We find that the probability distribution of the sizes of the jumps and of the time intervals between them exhibit power-law behaviour over two decades. We develop a model of the inflation process in which 'avalanches' of airway openings are seen--with power-law distributions of both the size of avalanches and the time intervals between them--which agree quantitatively with those seen experimentally, and are reminiscent of the power-law behaviour observed for self-organized critical systems. Thus power-law distributions, arising from avalanches associated with threshold phenomena propagating down a branching tree structure, appear to govern the recruitment of terminal airspaces.

.-Hyperoxia-induced lung damage was investigated via airway and respiratory tissue mechanics measurements with low-frequency forced oscillations (LFOT) and analysis of spontaneous breathing indexes by barometric whole body plethysmography (WBP). WBP was performed in the unrestrained awake mice kept in room air (n ϭ 12) or in 100% oxygen for 24 (n ϭ 9), 48 (n ϭ 8), or 60 (n ϭ 9) h, and the indexes, including enhanced pause (Penh) and peak inspiratory and expiratory flows, were determined. The mice were then anesthetized, paralyzed, and mechanically ventilated. Airway resistance, respiratory system resistance at breathing frequency, and tissue damping and elastance were identified from the LFOT impedance data by model fitting. The monotonous decrease in airway resistance during hyperoxia correlated best with the increasing peak expiratory flow. Respiratory system resistance and tissue damping and elastance were unchanged up to 48 h of exposure but were markedly elevated at 60 h, with associated decreases in peak inspiratory flow. Penh was increased at 24 h and sharply elevated at 60 h. These results indicate no adverse effect of hyperoxia on the airway mechanics in mice, whereas marked parenchymal damage develops by 60 h. The inconsistent relationships between LFOT parameters and WBP indexes suggest that the changes in the latter reflect alterations in the breathing pattern rather than in the mechanical properties. It is concluded that, in the presence of diffuse lung disease, Penh is inadequate for characterization of the mechanical status of the respiratory system.

The pattern of lung response caused by intravenous Mch and Ova are fundamentally different. Although inhaled Mch induces a heterogeneous lung response similar to that observed with intravenous allergen, these similar patterns are due to different mechanisms.