A. First series of experiments: PEEP = 2 cmH 2 O Lung mechanics. The first series of experiments was performed at a PEEP = 2 cmH 2 O, a PEEP level that is commonly used in animal studies that aim to study VILI (see Table 1 ). Ventilation with 8 mL/kg and no RM (lowV T noRM) caused a continuous decrease of pulmonary compliance (C) over more than two hours that reached a plateau at approximately 30% of the physiological baseline value (Fig. 1 ). Within this time pulmonary resistance (R) nearly tripled. Resistance and compliance showed less dramatic trends in mice ventilated with 16 mL/kg and no RM (highV T noRM). In this group C plateaued earlier (60 min) at about 60% of the baseline value and R increased to a lesser degree (,25%). R and C differed significantly between the lowV T noRM and the highV T noRM group (R: p,0.01; C: p,0.001). Respiratory input impedance revealed major alterations in the periphery of the lung. Tissue damping (G) and tissue elastance (H) were elevated in both highV T noRM and lowV T noRM mice, reaching significantly higher values in the lowV T noRM group (G: p,0.01; H: p,0.001). In the latter group, airway resistance (R aw ) was increased as well. The increase in G, H and R aw indicates that low V T ventilation without RM leads to closure of peripheral areas of the lung and causes a small degree of airway constriction. In consequence, hysteresivity (G/H = g) decreased slightly over time, but was in a comparable range in all groups.