Preexposure to hyperoxia causes increased lung injury and epithelial apoptosis in mice ventilated with high tidal volumes

摘要: Both high tidal volume mechanical ventilation (HV) and hyperoxia (HO) have been implicated in ventilator-induced lung injury. However, patients with acute injury are often exposed to HO before the application of ventilation. The potential priming lungs for subsequent by exposure has not extensively studied. We provide evidence that (90%) 12 h followed HV (25 μl/g) combined 2 or 4 (HO-12h+HVHO-2h -4h) induced severe mice. Analysis homogenates showed was associated cleavage executioner caspases, caspases-3 -7, their downstream substrate poly(ADP-ribose) polymerase-1 (PARP-1). No significant caspase seen either 16 up h. Ventilation (HVHO) did cause without preexposure HO. Twelve-hour lower (6 failed produce cleavage. also evaluated initiator caspases-8 -9, determine whether death receptor mitochondrial-mediated pathways were involved. Caspase-9 observed HO-12h+HVHO-2h -4h as well Caspase-8 activation only HO-12h+HVHO-4h, indicating involvement both pathways. Immunohistochemistry vitro stretch studies alveolar epithelial cells. In conclusion, produced cell apoptosis.