Altered alveolar mechanics in the acutely injured lung

Objectives: Alterations in alveolar mechanics (i.e., the dynamic change in alveolar size during tidal ventilation) are thought to play a critical role in acute lung injuries such as acute respiratory distress syndrome (ARDS). In this study, we describe and quantify the dynamic changes in alveolar me chanics of individual alveoli in a porcine ARDS model by direct visualizati on using in vivo microscopy. Design: Prospective, observational, controlled study. Setting: University research laboratory. Subjects: Ten adult pigs. Interventions: Pigs were anesthetized and placed on mechanical ventilation, underwent a left thoracotomy, and were separated into the following two gr oups post hoc: a control group of instrumented animals with no lung injury (n = 5), and a lung injury group in which lung injury was induced by trache al Tween instillation, causing surfactant deactivation (n = 5). Pulmonary a nd systemic hemodynamics, blood gases, lung pressures, subpleural blood flo w (laser Doppler), and alveolar mechanics (in vivo microscopy) were measure d in both groups. Alveolar size was measured at peak inspiration (I) and en d expiration (E) on individual subpleural alveoli by image analysis. Histol ogic sections of lung tissue were taken at necropsy from the injury group. Measurements and Main Results: In the acutely injured lung, three distinct alveolar inflation-deflation patterns were observed and classified: type I alveoli (n = 37) changed size minimally (I - E Delta = 367 +/- 88 mum(2)) d uring tidal ventilation; type II alveoli (n = 37) changed size dramatically (I - E Delta = 9326 +/- 1010 mum(2)) with tidal ventilation but did not to tally collapse at end expiration; and type III alveoli (n = 12) demonstrate d an even greater size change than did type II alveoli (I - E Delta = 15,41 8 +/- 1995 mum(2)), and were distinguished from type II in that they totall y collapsed at end expiration (atelectasis) and reinflated during inspirati on. We have termed the abnormal alveolar inflation pattern of type II and I II alveoli "repetitive alveolar collapse and expansion" (RACE). RACE descri bes all alveoli that visibly change volume with ventilation, regardless of whether these alveoli collapse totally (type III) at end expiration. Thus, the term "collapse" in RACE refers to a visibly obvious collapse of the alv eolus during expiration, whether this collapse is total or partial. In the normal lung, all alveoli measured exhibited type I mechanics. Alveoli were significantly larger at peak inspiration in type II (18,266 +/- 1317 mum(2) , n = 37) and III (15,418 +/- 1995 mum(2), n = 12) alveoli as compared with type I (8214 +/- 655 mum(2), n = 37). Tween caused a heterogenous lung inj ury with areas of normal alveolar mechanics adjacent to areas of abnormal a lveolar mechanics. Subsequent histologic sections from normal areas exhibit ed no pathology, whereas lung tissue from areas with RACE mechanics demonst rated alveolar collapse, atelectasis, and leukocyte infiltration. Conclusion: Alveolar mechanics are altered in the acutely injured lung as d emonstrated by the development of alveolar instability (RACE) and the incre ase in alveolar size at peak inspiration. Alveolar instability varied from alveolus to alveolus in the same microscopic field and included alveoli tha t changed area greatly with tidal ventilation but remained patent at end ex piration and those that totally collapsed and reexpanded with each breath. Thus, alterations in alveolar mechanics in the acutely injured lung are com plex, and attempts to assess what may be occurring at the alveolar level fr om analysis of inflection points on the whole-lung pressure/volume curve ar e likely to be erroneous. We speculate that the mechanism of ventilator-ind uced lung injury may involve altered alveolar mechanics, specifically RACE and alveolar overdistension.