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

常规机械通气（CMV）本身可导致肺损伤的产生或恶化。高频振荡（HFO）已被公认为是一种有效的治疗策略，以减少肺损伤的呼吸支持。使用表面活性剂耗尽的成年家兔模型进行了几项研究，以比较HFO和CMV之间的差异。从这些研究中，CMV已被证明导致氧合不良，肺顺应性降低，肺灌洗液中多形核白细胞（PMN）数量增加，以及肺的实质性变化，包括透明膜形成和PMN积聚。相比之下，HFO提供了极好的氧合，而没有PMN的积累，并且肺中的透明膜形成较少。此外，与HFO相反，CMV导致PMN浸润和活化增加，并增加肺灌洗液中细胞因子（如PAF和TBX）的水平。第一年，我们在CMV诱导的肺损伤模型中研究类固醇是否可以通过阻止化学介质的释放来减轻肺损伤。结果表明：激素组肺灌洗液中PMN数、TXB_2、6-keto-PGF_1 α和TNF-α含量均低于对照组。静脉注射类固醇的PaO_2组高于对照组。这些结果表明，类固醇可以阻止化学介质的释放，导致肺损伤轻。第二年，我们假设在一个表面活性剂耗尽的肺模型中，4 hrs-CMV后灌洗液中的TNF-α的主要来源是PMN，其浸润到肺泡。应用抗TNF-α多克隆抗体进行免疫荧光染色，结果表明，在肺表面细胞耗竭模型中，从通气4小时后的灌洗液中分离出的PMN与TNF-α呈阳性反应。

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.