Cargando…

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

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 e...

Descripción completa

Detalles Bibliográficos
Autores principales: Sato, Susumu, Bartolák-Suki, Erzsébet, Parameswaran, Harikrishnan, Hamakawa, Hiroshi, Suki, Béla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428081/
https://www.ncbi.nlm.nih.gov/pubmed/26029115
http://dx.doi.org/10.3389/fphys.2015.00146
_version_ 1782370834370789376
author Sato, Susumu
Bartolák-Suki, Erzsébet
Parameswaran, Harikrishnan
Hamakawa, Hiroshi
Suki, Béla
author_facet Sato, Susumu
Bartolák-Suki, Erzsébet
Parameswaran, Harikrishnan
Hamakawa, Hiroshi
Suki, Béla
author_sort Sato, Susumu
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4428081
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-44280812015-05-29 Scale dependence of structure-function relationship in the emphysematous mouse lung Sato, Susumu Bartolák-Suki, Erzsébet Parameswaran, Harikrishnan Hamakawa, Hiroshi Suki, Béla Front Physiol Physiology 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. Frontiers Media S.A. 2015-05-12 /pmc/articles/PMC4428081/ /pubmed/26029115 http://dx.doi.org/10.3389/fphys.2015.00146 Text en Copyright © 2015 Sato, Bartolák-Suki, Parameswaran, Hamakawa and Suki. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Sato, Susumu
Bartolák-Suki, Erzsébet
Parameswaran, Harikrishnan
Hamakawa, Hiroshi
Suki, Béla
Scale dependence of structure-function relationship in the emphysematous mouse lung
title Scale dependence of structure-function relationship in the emphysematous mouse lung
title_full Scale dependence of structure-function relationship in the emphysematous mouse lung
title_fullStr Scale dependence of structure-function relationship in the emphysematous mouse lung
title_full_unstemmed Scale dependence of structure-function relationship in the emphysematous mouse lung
title_short Scale dependence of structure-function relationship in the emphysematous mouse lung
title_sort scale dependence of structure-function relationship in the emphysematous mouse lung
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428081/
https://www.ncbi.nlm.nih.gov/pubmed/26029115
http://dx.doi.org/10.3389/fphys.2015.00146
work_keys_str_mv AT satosusumu scaledependenceofstructurefunctionrelationshipintheemphysematousmouselung
AT bartolaksukierzsebet scaledependenceofstructurefunctionrelationshipintheemphysematousmouselung
AT parameswaranharikrishnan scaledependenceofstructurefunctionrelationshipintheemphysematousmouselung
AT hamakawahiroshi scaledependenceofstructurefunctionrelationshipintheemphysematousmouselung
AT sukibela scaledependenceofstructurefunctionrelationshipintheemphysematousmouselung