Protective ventilation comprised 8 ml/kg VT and titration selleck chem of PEEP such that the plateau pressure (Pplat) was 30 cmH2O . These settings were based on a clinically relevant strategy aimed at maximizing alveolar recruitment while limiting hyperinflation . Injurious ventilation consisted of zero PEEP (0 cmH2O) and titrated VT, such that Pplat was 30 cmH2O. This strategy was aimed at producing both cyclic recruitment-derecruitment and volutrauma while limiting hyperinflation by applying the same Pplat levels used in the protective strategy. Volume-controlled ventilation was used in all cases.A recruitment maneuver (continuous positive airway pressure of 40 cmH2O during 40 s ) was performed at the beginning of the experiment, before adjusting PEEP or VT.
Inspired fraction of oxygen (FiO2) was titrated to a target arterial oxygen saturation greater than 88%, a 1:2 inspiratory-to-expiratory time ratio and an 18 breaths/min respiratory rate and adjusted to maintain arterial carbon dioxide tension at 32 to 45 mmHg.Positron emission tomography imaging protocol and processingThe imaging methods and analysis we used have been described in detail previously [10,22-24]. PET images consisted of 15 axial slices (slice thickness = 6.5 mm), corresponding to approximately 70% of the lung . Three different modalities of PET scans were performed: (1) transmission scans to correct for attenuation in emission scans and to calculate fgas from regional tissue density, which was used to categorize the pulmonary parenchyma as nonaerated (fgas < 0.1), poorly aerated (0.1 �� fgas < 0.
5), normally aerated (0.5 �� fgas < 0.85) and hyperinflated (fgas �� 0.85) ; (2) 13N[nitrogen] (13NN) emission scans using a bolus injection of 13NN-saline to measure regional pulmonary perfusion and shunt fraction [23,26]; and (3) 18F-FDG emission scans to quantify regional metabolic activity using 18F-FDG kinetics. Doses of 5 to 10 mCi of 18F-FDG were infused for 60 s at a constant rate through the central venous catheter. Acquisition time of the dynamic PET scans was 75 min starting simultaneously with the beginning of 18F-FDG infusion.The lung field was delineated using perfusion and gas fraction images [11,27,28]. The whole field was divided for analysis into three horizontal adjacent regions of interest (ROIs) of equal vertical height (nondependent, middle and dependent).
Modeling of 18F-fluorodeoxyglucose kineticsInside cells, 18F-FDG is phosphorylated by hexokinase to 18F-FDG-6-phosphate, which accumulates in proportion to cellular metabolic rate. 18F-FDG net uptake rate was calculated by fitting the 18F-FDG kinetics with the Sokoloff three-compartment model for three Anacetrapib isogravitational ROIs defined along the vertical axis: dependent, middle and nondependent .