Scale dependence of structure-function relationship in the emphysematous mouse lung

Abstract

The purpose of this study was to determine how the initial distribution of elastase in mouse lungs determines the time course of tissue destruction and how structural heterogeneity at different spatial scales influences lung function. We evaluated lung function and alveolar structure in normal and emphysematous C57BL/6 mice at 2 and 21 days following orotracheal treatment with porcine pancreatic elastase (PPE). Initial distribution of elastase 1 h after treatment was assessed using red fluorescently labeled PPE (f-PPE) by laser scanning confocal microscopy. From measured input impedance of the respiratory system, the global lung compliance, and the variability of regional compliance were obtained. Lungs were fixed and equivalent airspace diameters were measured in four lobes of the right lung and three regions of the left lung. At day 2 and day 21, the mean airspace diameter of each region was significantly enlarged which was accompanied by an increased inter-regional heterogeneity. The deposition of f-PPE on day 0 was much more heterogeneous than the inter-regional diameters at both day 2 and day 21 and, at day 21, this reached statistical significance (p < 0.05). Microscale heterogeneity characterized by the overall variability of airspace diameters correlated significantly better with compliance than macroscale or inter-regional heterogeneity. Furthermore, while the spatial distribution of the inflammatory response does not seem to follow that of the elastase deposition, it correlates with the strongest regional determinant of lung function. These results may help interpret lung function decline in terms of structural deterioration in human patients with emphysema.

Comparative morphometric analysis of lungs of the semifossorial giant pouched rat (Cricetomys gambianus) and the subterranean Nigerian mole rat (Cryptomys foxi)

“…They also resembled those of surface-and underground dwelling rodents 114,115 . The undivided left lung of C. gambianus, which was also reported in the same rodent by Ibe et al 60 , and the existence of three lobes on the left lung of C. foxi are not unique morphological features: various permutations in the lobulations of the lung occur in the mammalian lungs 61,62,113,[116][117][118][119][120][121] . Ostensibly, there is no evidence showing that lobulation of the lung is of functional consequence [122][123][124][125][126][127][128][129][130][131][132][133][134] .…”

Quantification of image texture in X‐ray phase‐contrast‐enhanced projection images of in vivo mouse lungs observed at varied inflation pressures

“…Analyzing the appearance of defined structural changes may be an avenue for assaying regional changes in physiological functions. For example, because the right mouse lung comprises four distinct lobes that can differ in compliance, ventilation, and blood flow (Irvin and Bates, ; Sato et al, ; Meyerholz et al, ), the capacity of the microstructure to expand in three‐dimensions varies from lobe to lobe. One might therefore expect some corresponding difference in the image texture observed in a projection image.…”

Identification of Mepenzolate Derivatives With Long-Acting Bronchodilatory Activity

“…In this study, we used intratracheal administration of each drug, because this method is convenient for experiments. However, it is possible that the compound does not distribute evenly through this method ( Tanaka et al, 2010 ; Sato et al, 2015 ). The patchy appearance of airspace enlargement on the histological section following treatment with MP-AD may be explained by this uneven distribution of the drug.…”