Rosenthal C, Caronia C, Quinn C, Lugo N, Sagy M
Division of Critical Care Medicine, Schneider Children's Hospital, New Hyde Park, NY 11040, USA.
Crit Care Med. 1998 May;26(5):912-6. doi: 10.1097/00003246-199805000-00027.
To compare four widely used animal models of acute lung injury and to determine the changes in physiologic variables associated with each model.
A prospective, controlled animal study.
An animal laboratory of a university-affiliated children's hospital.
Four groups of anesthetized, paralyzed, and ventilated young Yorkshire pigs, weighing 35 to 45 kg.
Acute lung injury was generated by four different methods: a) intrapulmonary arterial infusion of endotoxin of Escherichia colt; b) bronchoalveolar instillation of 0.05N of hydrochloric acid; c) repeated bronchoalveolar warm saline lavage; and d) intrapulmonary arterial infusion of oleic acid. After each acute lung injury procedure, the temporal changes in various physiologic variables were measured, starting at 60 mins and at 15-min intervals thereafter for a total of 165 mins. Systemic and mixed venous serum immunoreactive tumor necrosis factor (TNF)-alpha concentrations were also measured at the same time points. Analysis of variance for repeated measures was employed to determine the absolute and relative significance of the changes observed.
Systemic and mixed venous immunoreactive TNF-alpha did not change following any of the acute lung injury procedures. The animals' heart rates and systemic vascular resistances also did not change. Hydrochloric acid instillation as well as bronchoalveolar lavage resulted in significant hypoxemia with no other hemodynamic effects. Endotoxin infusion did not result in hypoxemia but caused significant increases in mean pulmonary arterial pressure and pulmonary vascular resistance and decreases in mean arterial pressure and cardiac output. Oleic acid infusion resulted in a marked hypoxemia with a pronounced increase in mean pulmonary arterial pressure and pulmonary vascular resistance. It also markedly reduced the mean arterial pressure, cardiac output, and the mixed venous PO2.
The surfactant depletion and hydrochloric acid instillation models produce acute hypoxemia in an otherwise hemodynamically stable animal. A brief endotoxin infusion provides a model for cardiovascular instability and pulmonary hypertension but fails to produce hypoxemia in the pig. The oleic acid infusion creates a model of marked cardiovascular instability, pulmonary hypertension, and profound hypoxemia. However, none of the acute lung injury models described was associated with the production of tumor necrosis factor.
比较四种广泛应用的急性肺损伤动物模型，并确定与每种模型相关的生理变量变化。
一项前瞻性对照动物研究。
一所大学附属医院的动物实验室。
四组麻醉、麻痹并接受通气的年轻约克夏猪，体重35至45千克。
通过四种不同方法引发急性肺损伤：a）经肺动脉注入大肠杆菌内毒素；b）支气管肺泡内滴注0.05N盐酸；c）重复支气管肺泡温盐水灌洗；d）经肺动脉注入油酸。在每次急性肺损伤操作后，从60分钟开始，此后每隔15分钟测量各种生理变量的时间变化，共测量165分钟。同时在相同时间点测量全身和混合静脉血清免疫反应性肿瘤坏死因子（TNF）-α浓度。采用重复测量方差分析来确定观察到的变化的绝对和相对显著性。
在任何急性肺损伤操作后，全身和混合静脉免疫反应性TNF-α均未改变。动物的心率和全身血管阻力也未改变。滴注盐酸以及支气管肺泡灌洗导致显著低氧血症，无其他血流动力学影响。注入内毒素未导致低氧血症，但导致平均肺动脉压和肺血管阻力显著升高，平均动脉压和心输出量降低。注入油酸导致明显低氧血症，平均肺动脉压和肺血管阻力显著升高。它还显著降低了平均动脉压、心输出量和混合静脉血氧分压。
表面活性剂耗竭和盐酸滴注模型在血流动力学稳定的动物中产生急性低氧血症。短暂注入内毒素提供了心血管不稳定和肺动脉高压的模型，但在猪中未能产生低氧血症。注入油酸创建了显著心血管不稳定、肺动脉高压和严重低氧血症的模型。然而，所描述的急性肺损伤模型均与肿瘤坏死因子的产生无关。
