The purpose of this study is to compare pulmonary nuclear factor-kappaB (NF-kappaB) activity of conventional mechanical ventilation (CMV) with that of high-frequency oscillation (HFO) in premature rabbit lungs. For surfactant-depleted model, we used premature rabbits in order to exclude the effect of lung lavage on the activation of NF-kappaB. The premature rabbits were delivered at a gestational age of 27 days by hysterotomy. Both modes of the ventilator were set at the same MAP and FiO(2). We used animals that had PCO(2) levels of approximately 50-mmHg. Animals were sacrificed after 1-hr ventilation with CMV or HFO. Then activity of pulmonary NF-kappaB was assessed. We observed that NF-kappaB activity was higher in the lungs of CMV compared with those of HFO, as measured by Western blot analysis. The activity level of NF-kappaB in the lungs measured by ELISA was significantly higher in CMV group than in HFO group. We conclude that a higher level of NF-kappaB activation was associated with CMV when compared to HFO.

High-frequency oscillation (HFO) has been recognized as an effective ventilatory strategy to minimize lung injury during respiratory support. Conventional mechanical ventilation (CMV) compared with HFO was shown to result in an increased number of PMNs and inflammatory cytokines in the lung lavage fluid. However how mechanical forces can be sensed by cells and converted into biochemical signals for intracellular signal transduction is still unknown. In this current study, we sought to determine whether the activation of Nuclear factor-kappa B (NF-kappaB) might be involved in the lung injury caused by CMV. Surfactant-depleted Japanese white rabbits received 1- or 4-hr CMV or 1- or 4-hr HFO. Then, activation of NF-kappaB in the lungs was assessed by conducting electrophoretic mobility shift assays (EMSA). In the experiment with whole lungs, NF-kappaB activity was much higher in the 4-hr CMV lungs than in the 4-hr HFO lungs. To clarify the origin of the cells in which NF-kappaB was activated, we did a second lung lavage at the end of ventilation and washed out the cells that had infiltrated the alveoli. The levels of NF-kappaB activity were the similar in the lungs of 4-hr HFO rabbits and in those of 4-hr CMV ones. On the other hand, NF-kappaB activity was much higher in the 4-hr CMV lungs than in the 4-hr HFO lungs in the experiment with the lung lavage fluid cells. These results show that the increase in NF-kappaB activity in the lungs of 4-hr CMV rabbits was due mainly to the cells that had infiltrated the alveoli.

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