title: From morphological heterogeneity at alveolar level to the overall mechanical lung behavior: an in vivo microscopic imaging study.
abstract: In six male anesthetized, tracheotomized, and mechanically ventilated rabbits, we imaged subpleural alveoli under microscopic view (60×) through a "pleural window" obtained by stripping the endothoracic fascia and leaving the parietal pleura intact. Three different imaging scale levels were identified for the analysis on increasing stepwise local distending pressure (P ld) up to 16.5 cmH2O: alveoli, alveolar cluster, and whole image field. Alveolar profiles were manually traced, clusters of alveoli of similar size were identified through a contiguity-constrained hierarchical agglomerative clustering analysis and alveolar surface density (ASD) was estimated as the percentage of air on the whole image field. Alveolar area distributions were remarkably right-skewed and showed an increase in median value with a large topology-independent heterogeneity on increasing P ld. Modeling of alveolar area distributions on increasing P ld led to hypothesize that absolute alveolar compliance (change in surface area over change in P ld) increases fairly linearly with increasing initial alveolar size, the corollary of this assumption being a constant specific compliance. Clusters were reciprocally interweaved due to their highly variable complex shapes. ASD was found to increase with a small coefficient of variation (CV <25%) with increasing P ld. The CV of lung volume at each transpulmonary pressure was further decreased (about 6%). The results of the study suggest that the considerable heterogeneity of alveolar size and of the corresponding alveolar mechanical behavior are homogenously distributed, resulting in a substantially homogenous mechanical behavior of lung units and whole organ.
authors.affiliation: TBM Lab, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Mazzuca
authors.affiliation: TBM Lab, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Salito
authors.affiliation: Department of Health Sciences, Università di Milano-Bicocca, Monza, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Rivolta
authors.affiliation: TBM Lab, Dipartimento di Elettronica, Informazione e Bioingegneria, Politecnico di Milano, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Aliverti
authors.affiliation: Department of Health Sciences, Università di Milano-Bicocca, Monza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Miserocchi
keywords: Alveolar mechanics; in vivo microscopy; multiscale
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1979 Nov;47(5):990-1001
references.pmid: 511725
references.citation: J Appl Physiol (1985). 2005 Dec;99(6):2388-97
references.pmid: 16081622
references.citation: Respir Physiol Neurobiol. 2011 Sep 15;178(2):283-9
references.pmid: 21762792
references.citation: J Appl Physiol. 1970 Nov;29(5):705-12
references.pmid: 5474864
references.citation: J Appl Physiol (1985). 2005 Aug;99(2):723-30
references.pmid: 15831795
references.citation: J Appl Physiol (1985). 2008 Feb;104(2):338-46
references.pmid: 18006870
references.citation: Am J Respir Crit Care Med. 2003 Sep 1;168(5):516-21
references.pmid: 12941655
references.citation: Eur Respir J. 2011 Apr;37(4):943-9
references.pmid: 20693242
references.citation: J Appl Physiol (1985). 2013 Jul 1;115(1):64-70
references.pmid: 23599394
references.citation: J Appl Physiol Respir Environ Exerc Physiol. 1982 Apr;52(4):1064-70
references.pmid: 7085408
references.citation: Am J Respir Cell Mol Biol. 2008 May;38(5):572-8
references.pmid: 18096874
references.citation: J Biomed Opt. 2010 Jan-Feb;15(1):016030
references.pmid: 20210474
references.citation: J Appl Physiol (1985). 1985 Aug;59(2):623-33
references.pmid: 4030616