From morphological heterogeneity at alveolar level to the overall mechanical lung behavior: an in vivo microscopic imaging study

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 cmH 2 O: 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.