Increasing the inspiratory time and I:E ratio reduced oxygenation capacity in VILI. Mice were mechanically ventilated for 4 hours with either low tidal volume (LVT 9 ml/kg) or high tidal volume (HVT 34 ml/kg) and an inspiratory/expiratory ratio of 1:2 or 1:1, respectively. An alternative end point was defined as decreasing of mean arterial blood pressure below 40 mm Hg, which predicts death with certainty in this model. Controls (ctr) were subjected to LVT 1:2 ventilation only during operation and were killed before the 4-hour ventilation protocol started. (A) Pulse oximetry revealed stable oxygen saturation in LVT 1:2, LVT 1:1, and HVT 1:2 groups, whereas the HVT 1:1 ventilated mice developed a decrease of oxygen saturation during the 4-hour ventilation period. End-point measurements of arterial partial pressure of oxygen were performed, and the P/F ratio (B), and the oxygenation index were calculated (C). n = 13 to 14 in each group; ***P < 0.001.