The development of various forms of lung injury with increasing tidal volume in normal rats

Sixty-three, open-chest normal rats were subjected to mechanical ventilation (MV) with tidal volumes (V_T) ranging from 7.5-39.5ml kg^-1 and PEEP 2.3 cmH₂O. Arterial blood gasses and pressure, and lung mechanics were measured during baseline ventilation (V_T = 7.5ml kg^-1) before and after test ventilation, when cytokine, von Willebrand factor (vWF), and albumin concentration in serum and broncho-alveolar lavage fluid (BALF), wet-to-dry weight ratio (W/D), and histologic injury scores were assessed. Elevation of W/D and serum vWF and cytokine concentration occurred with V_T > 25ml kg^-1. With V_T > 30ml kg^-1 cytokine and albumin concentration increased also in BALF, arterial oxygen tension decreased, lung mechanics and histology deteriorated, while W/D and vWF and cytokine concentration increased further. Hence, the initial manifestation of injurious MV consists of damage of extra-alveolar vessels leading to interstitial edema, as shown by elevated vWF and cytokine levels in serum but not in BALF. Failure of the endothelial-epithelial barrier occurs at higher stress-strain levels, with alveolar edema, small airway injury, and mechanical alterations.