Research on pathophysiology and prevention of ventilator induced lung injury in neonates.

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Conventional mechanical ventilation (CMV) can by itself lead to the production or worsening of lung injury. High frequency oscillation (HFO) has been recognized as an effective ventilatory strategy to minimize lung injury in respiratory support. Several studies using the surfactant-depleted adult rabbit model were performed to compare the differences between HFO and CMV.From those studies, CMV has been shown to result in poor oxygenation, decreased lung compliance, increased number of polymorphonuclear leukocytes (PMN) in the lung lavage fluid, and substantial changes in the lungs, including hyaline membrane formation and PMN accumulation. In contrast, HFO provides excellent oxygenation without the accumulation of PMN and with less hyaline membrane formation in the lungs. Further, as opposed to HFO, CMV leads to increased PMN infiltration and activation and to increased lung lavage levels of cytokines, such as PAF and TBX.First year, we did the study whether steroid could reduce lung injury by preventing the release of chemical mediators or not in this CMV-induced lung injury model. The results were that the numbers of PMN, and the levels of TXB_2,6-keto-PGF_1 α and TNF-α in lung lavage fluid were lower in steroid groups than in control group. PaO_2 of steroid (I.V.) group was higher than that of control group. These results suggest that steroid could prevent the release of chemical mediators and result in less lung injury.Second year, we hypothesized that in a surfactant-depleted lung model the major source of TNF-α in the lavage fluid after 4 hrs-CMV are PMN which were infiltrated into alveoli. We performed immunofluorescent staining using a polyclonal anti-TNF-α antibody to demonstrate a positive reaction with PMN separated from lavaged fluid after 4hrs ventilation in surfactant-depleted model.