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

新生儿呼吸机所致肺损伤的病理生理学及预防研究

基本信息

批准号：
11671073
负责人：
KAWANO Toshio
金额：
$ 1.86万
依托单位：
Kyorin University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671073/
关键词：
mechanical ventilation surfactant-depleted lung steroid polymorphonuclear leukocyte lung injury

项目摘要

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.

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通气策略，以减少呼吸支持中的肺损伤。使用表面活性剂缺失的成年兔模型进行了几项研究，以比较HFO和CMV之间的差异。这些研究表明，巨细胞病毒导致氧合不良，肺顺应性降低，肺灌洗液中多形核白细胞（PMN）数量增加，肺部发生实质性变化，包括透明膜形成和PMN积聚。相比之下，HFO提供了良好的氧合，没有PMN的积累，肺内透明膜的形成较少。此外，与HFO相反，巨细胞病毒导致PMN浸润和激活增加，并导致细胞因子（如PAF和TBX）肺灌洗水平增加。第一年，我们在cmv诱导的肺损伤模型中研究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。结果表明：类固醇组大鼠肺灌洗液中PMN数量、TXB_2、6-酮- pgf_1 α、TNF-α水平均低于对照组；类固醇（静脉注射）组PaO_2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，减少肺损伤。第二年，我们假设在表面活性剂缺失的肺模型中，cmv 4小时后灌洗液中TNF-α的主要来源是浸润到肺泡的PMN。我们使用多克隆抗tnf -α抗体进行免疫荧光染色，证实在缺乏表面活性剂的模型中，通气4小时后从灌洗液中分离的PMN有阳性反应。