Airway-parenchymal interdependence in the lung slice

Abstract

The explanted lung slice has become a popular in vitro system for studying how airways contract. Because the forces of airway-parenchymal interdependence are such important modulators of airway narrowing, it is of significant interest to understand how the parenchyma around a constricting airway in a lung slice behaves. We have previously shown that the predictions of the 2-dimensional distortion field around a constricting airway are substantially different depending on whether the parenchyma is modeled as an elastic continuum versus a network of hexagonally arranged springs, which raises the question as to which model best explains the lung slice. We treated lung slices with methacholine and then followed the movement of a set of parenchymal landmarks around the airway as it narrowed. The resulting parenchymal displacement field was compared to the displacement fields predicted by the continuum and hexagonal spring network models. The predictions of the continuum model were much closer to the measured data than were those of the hexagonal spring network model, suggesting that the parenchyma in the lung slice behaves like an elastic continuum rather than a network of discrete springs. This may be because the alveoli of the lung slice are filled with agarose in order to provide structural stability, causing the parenchyma in the slice to act like a true mechanical continuum. How the air-filled parenchyma in the intact lung behave in vivo remains an open question.

Figure 1

Images of the high-dose lung slice before airway constriction (left), in the fully constricted state (middle), and after the methacholine (1000 nM) was washed away to allow the airway to relax (right). The hatched structures in the periphery of the image are nylon mesh that anchored the borders of the slice in place.

Figure 2

A) The hexagonal spring network model of the parenchyma with an airway at its center. Each linear element in the model represents a spring with a specified stiffness and elastic equilibrium (zero stress) length. B) The continuum model showing the mesh used to calculate parenchymal properties. The mesh becomes finer nearer the airway border in order to accurately model the inward movement of the parenchyma near the contracting airway.

Figure 3

Comparison of the time-history of airway lumen area during airway contraction between experiments and spring network model.

Figure 4

Parenchymal displacement field showing the movements of each landmark that occurred over the course of airway narrowing in the high-dose slice. Arrows indicate direction and distance of movement.

Figure 5

Comparison of normalized displacement fields between the low-dose slice and high-dose slice experimental data sets and the continuum model when the ratio of parenchyma to airway size in the model is comparable to that of the lung slice.

Figure 6

Comparison of normalized displacement field between the low-dose slice and high-dose slice experimental data sets and the hexagonal spring network model when the ratio of network to airway size in the model is comparable to that of the lung slice. Also shown is the prediction of the spring network model when the dimensions of the parenchymal network are increased 3 fold and the results are plotted with the normalized radial distance reduced by 3 fold.