Table 2Baseline mechanical dataaTable 3Mechanical data at endaTable 4Arterial blood gases at EPZ-5676 clinical trial baseline zero end-expiratory pressure and endaIn ALIp, alveolar collapse was higher at BIVENT-100 compared to PCV and lower at BIVENT-50 than at BIVENT-100 and BIVENT-75. In ALIexp, alveolar collapse was lower at BIVENT-50 than the other ventilatory strategies (Table 5 and Figure 5).Table 5Lung morphometryaFigure 5Photomicrographs of lung parenchyma stained with hematoxylin and eosin. Photomicrographs are representative of data obtained from lung sections of six animals (original magnification, ��200). ALIexp: extrapulmonary acute lung injury; ALIp: pulmonary …The semiquantitative analysis of lung and diaphragm electron microscopy is shown in Table 6 and Figures 6 and and7.7.

In the ALIp group, BIVENT-75 and BIVENT-50 resulted in reduced damage to alveolar capillary membranes, type II epithelial cells and endothelial cells compared to PCV. In ALIexp, BIVENT-75 reduced type II epithelial and endothelial cell damage, and BIVENT-50 reduced alveolar capillary membrane and type II epithelial cell damage, compared to PCV. In ALIp, mechanical ventilation led to myofibril damage with Z-disk edema, which was greater under PCV and BIVENT-100 than with other ventilator strategies. Mitochondrial injury of the diaphragm was less pronounced with BIVENT-50 than with BIVENT-100. Vacuoles were more abundant under PCV than under NV. BIVENT-50 resulted in a lower number of vacuoles and less diaphragm damage than other ventilator strategies. In the ALIexp group, Z-disk edema was more pronounced during PCV and BIVENT-50 than during NV.

Mitochondrial injury was more intense under PCV than under NV, but there were no differences in mitochondrial injury among different ventilator strategies. BIVENT-100 and BIVENT-75 resulted in fewer vacuoles and less intermyofibril space than were caused by PCV.Figure 6Electron microscopy of lung parenchyma. Photomicrographs are representative of data obtained from lung sections of five animals per group. Black arrows: alveolar capillary basement (ACB) membrane. Note that endothelial cells as well as alveolar types …Table 6Semiquantitative analysis of lung and diaphragm electron microscopyaFigure 7Electron microscopy of diaphragm. Photomicrographs are representative of data obtained from diaphragm sections of five animals Drug_discovery per group. In ALIp animals ventilated with PCV or BIVENT-100, note the presence of vacuoles. Conversely, in ALIexp, there were …In both ALI models, BIVENT decreased the gene expression of interleukin 6 (IL-6), IL-1��, procaspase 3, PCIII, ICAM-1 and RAGE in lung tissue compared to PCV (Figure 8). In ALIp, gene expression of IL-6 and PCIII was lower in all BIVENT groups compared to PCV.