Accordingly, ranges of -1000 to -900 Hounsfield units (HU), -900 to -500 HU, -500 to -100 HU, and -100 to +100 HU were used to define the hyperaerated, normally aerated, poorly aerated, and nonaerated compartments, respectively.Tidal Pazopanib reaeration was calculated as the decrease in the percentage of nonaerated and poorly aerated compartments from end-expiration to end-inspiration [14]. Tidal hyperaeration was calculated as the increase in the percentage of hyperaeration from end-expiration to end-inspiration [14].Ventilation in one zone of a given level was computed as the variation of gas content between end-inspiration and end-expiration of that zone divided by the total variation of gas content in the respective level.

For BIPAP+SBmean, CT variables were computed in the same way as for respiratory parameters, that is weighted means of spontaneous and controlled breaths.Protocol for measurementsAfter preparation, animals were allowed to stabilize for 15 minutes (baseline, volume-controlled mode). ALI was induced by means of surfactant depletion [15] and considered stable if partial pressure of oxygen (PaO2)/FiO2 was 200 mmHg or less for at least 30 minutes (injury, volume-controlled mode). After obtaining the measurements at injury, BIPAP+SBcontrolled was initiated as follows: the driving pressure, which corresponded to the difference between the higher and the lower continuous positive Paw level of 5 cmH2O, was set to obtain VT of 7 to 8 ml/kg and mechanical RR was set to reach partial pressure of carbon dioxide (PaCO2) in the range of 50 to 60 mmHg, without spontaneous breathing.

The I:E ratio was set to achieve mean Paw in the range of 8 to 10 cmH2O, as expected in PSV. At the same time, depth of anesthesia was a reduced, remaining constant thereafter. Lower mechanical RR combined with reduced depth of anesthesia enabled spontaneous breathing (unsynchronized and superimposed to BIPAP+SBcontrolled). When spontaneous breathing represented 20% or more of total minute ventilation, all animals were subjected to BIPAP+SBmean and PSV in randomized sequence for 60 minutes. During BIPAP+SBmean, the initial ventilatory settings of BIPAP+SBcontrolled were kept unchanged and spontaneous breathing efforts and rate increased according to the respiratory drive of the animals, without pressure support.

During PSV, the target pressure support was set to achieve VT of 7 to 8 ml/kg, the inspiratory flow GSK-3 trigger was fixed at 2.0 L/min and the ventilator cycled-off at 25% of peak flow. Each assisted mechanical ventilation mode lasted 60 minutes. Measurements were performed at the following steps: baseline, injury and at the end of each assisted mechanical ventilation mode. The time elapsed between stabilization of injury, and first and second assisted mechanical ventilation mode corresponded to 60 and 120 minutes, respectively.StatisticsData are given as mean �� standard deviation.