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加重。高频振荡(HFO)已被认为是一种有效的呼吸支持中减少肺损伤的呼吸机策略。使用肺表面活性物质耗竭的成年兔模型进行了几项研究，以比较HFO和CMV之间的差异。在这些研究中，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，以及肺组织的实质性变化，包括透明膜形成和PMN聚集。相比之下，HFO提供了良好的氧合，没有PMN的积聚，肺内形成的透明膜也较少。此外，与HFO相反，CMV导致PMN渗透和活化增加，肺灌洗液中细胞因子水平增加，如PAF和TBX。第一年，我们在这个CMV诱导的肺损伤模型中进行了类固醇是否可以通过阻止化学介质的释放来减轻肺损伤的研究。结果表明，激素组肺灌洗液中中性粒细胞数量、TXB2、6-keto-PGF1α和肿瘤坏死因子-α水平均低于对照组。动脉血氧分压(PaO_2)治疗组明显高于对照组。这些结果表明，类固醇可以阻止化学介质的释放，导致较少的肺损伤。第二年，我们假设在表面活性物质耗竭的肺模型中，4h-CMV后灌洗液中肿瘤坏死因子-α的主要来源是渗入肺泡的中性粒细胞。我们用多克隆抗肿瘤坏死因子-α抗体进行免疫荧光染色，证明在肺表面活性物质耗竭模型中，4h后灌洗液中分离的中性粒细胞与中性粒细胞呈阳性反应。

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.