Low volume ventilation of pre-injured lungs degrades lung function via stress concentration and progressive alveolar collapse.

Mechanical ventilation can cause ventilation-induced lung injury (VILI). The concept of stress concentrations suggests that surfactant dysfunction-induced microatelectases might impose injurious stresses on adjacent, open alveoli and function as germinal centers for injury propagation. The aim of the present study was to quantify the histopathological pattern of VILI progression and to test the hypothesis that injury progresses at the interface between microatelectases and ventilated lung parenchyma during low positive end-expiratory pressure (PEEP) ventilation. Bleomycin was used to induce lung injury with microatelectases in rats. Lungs were then mechanically ventilated for up to 6 hours at PEEP=1cmH2 O and compared to bleomycin treated group ventilated protectively with PEEP=5cmH2 O to minimize microatelectases. Lung mechanics were measured during ventilation. Afterwards lungs were fixed at end-inspiration or end-expiration for design-based stereology. Prior to VILI, bleomycin challenge reduced the number of open alveoli (N(alvair,par)) by 29%. No differences between end-inspiration and end-expiration were observed. Collapsed alveoli clustered in areas with a radius up to 56 µm. After PEEP=5cmH2 O ventilation for 6 hours, N(alvair,par) remained stable while PEEP=1cmH2 O ventilation led to an additional loss of aerated alveoli by 26%, mainly due to collapse, with a small fraction partly edema filled. Alveolar loss strongly correlated to worsening of tissue elastance, quasi-static compliance and inspiratory capacity. The radius of areas of collapsed alveoli increased to 94 µm, suggesting growth of the microatelectases. These data provide evidence that alveoli become unstable in neighborhood of microatelectases which most likely occurs due to by stress concentration-induced local vascular leak and surfactant dysfunction.