Airway inhomogeneities contribute to apparent lung tissue mechanics during constriction

Abstract

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.

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…As the forces acting on the airways are proportional to the recoil pressures, diminished radial forces acting on airways during deflation will lead to smaller airways than before a deep inhalation, with a concomitant increase in resistance. Although bronchial provocation does not explicitly alter parenchymal tissue properties [44], it is likely that ASM participates in changes in both parenchymal and airway hysteresis. One important factor determining the magnitude of airway hysteresis is ASM tone and the response of that tone to the stretch induced by deep inspiration; this will be discussed later in the current study.…”

Sevoflurane and desflurane protect cholinergic-induced bronchoconstriction of hyperreactive airways in rabbits

“…Moreover, the increases in G observed during MCh infusions with fairly constant H can be attributed to the enhanced ventilation heterogeneities that develop in the lung periphery, which was consistently confirmed in previous studies by using foreign gases and imaging techniques. 5,21 In this scenario, neither of the volatile anesthetics had a detectable effect on the elevated G. Despite the strong bronchoprotective action of these agents on the central airway tone, this finding suggests that they have no affinity to prevent a heterogeneous deterioration of the peripheral airway function. Since we observed Volatile agents and bronchoconstriction 1013 a complete recovery in all mechanical parameters following each MCh challenge, no residual effect of MCh may have biased our results.…”

“…The Zrs was calculated as the load impedance of the wave tube. 20 Separation of airway and tissue mechanical properties A well-established and verified 20,21 linear model containing a frequency-independent airway resistance (Raw) and inertance in series with the tissue damping (G) and elastance (H) of a constant-phase tissue compartment 22 was fitted to the Zrs spectra by minimizing the weighted difference between the measured and the modelled impedance data:…”

Interactions between pulmonary hemodynamics and lung mechanics

“…2). This pattern of change suggests that the mechanism responsible for these findings is homogenous throughout in the lungs [46]. One possible interpretation of such results would be the derecruitment of lung units at low Pc levels, while the remaining communicating lung is homogenous and essentially unaltered.…”

“…Our study, conducted under well-controlled conditions, confirms the occurrence of BHR in the presence of left-heart failure [3][4][5]8], with the additional information that the airways display an enhanced reactivity to a constrictor agonist (serotonin) that is not acting on the cholinergic receptors directly. The changes in the Raw following serotonin challenges demonstrate the presence of a dose-dependent airway constriction, while the increases in G exceeding those in H are likely to be a consequence of severe ventilation heterogeneities [46].…”