Department of Anesthesiology and Critical Care, Dalhousie University Halifax, QEII Health Sciences Center, 1276 South Park St., 10 West Victoria, Halifax, NS, B3H 2Y9, Canada.
Anesth Analg. 2011 May;112(5):1139-46. doi: 10.1213/ANE.0b013e3182104dac. Epub 2011 Apr 7.
Strategies to attenuate ventilator-associated lung injury have been tested in various experimental methods of acute lung injury (ALI). Conclusions are often drawn from physiologic and biologic effects, but the influence of the model on these results is not known. Our aim in this study was to characterize frequently used models of experimental ALI.
Twenty Sprague Dawley rats were anesthetized and their lungs mechanically ventilated for 5 hours. Three models of ALI (surfactant washout, acid aspiration, and high tidal volume ventilation) were investigated with regard to hemodynamics, respiratory mechanics, gas exchange, lung pathology, and inflammatory reactions. Animals without ALI served as controls.
Five animals in each group were analyzed. Dynamic compliance and Pao(2)/fraction of inspired oxygen ratio decreased by at least 50% in all groups after 1 hour. Whereas compliance remained decreased in all models, oxygenation returned to baseline values in the lavage group after 5 hours. Diffuse alveolar damage was worse in the high tidal volume model and was not different between the control and lavage animals. Interleukin-6 was increased in bronchoalveolar lavage fluid in the aspiration and high tidal volume models.
Although comparable physiologic effects meeting acute respiratory distress syndrome criteria were achieved in all models, the biologic responses varied among lung injury models. The acid aspiration model created both respiratory and inflammatory responses typically seen in ALI; these data suggest that it may be the most clinically applicable model to study the intermediate-term effects of ventilator-associated lung injury in rats.
在各种急性肺损伤（ALI）的实验方法中，已经测试了减轻呼吸机相关性肺损伤的策略。结论通常是根据生理和生物学效应得出的，但模型对这些结果的影响尚不清楚。我们在这项研究中的目的是描述常用于实验性 ALI 的模型。
20 只 Sprague Dawley 大鼠被麻醉并接受机械通气 5 小时。对三种 ALI 模型（表面活性剂冲洗、酸吸入和大潮气量通气）进行了研究，涉及血流动力学、呼吸力学、气体交换、肺病理学和炎症反应。无 ALI 的动物作为对照。
每组 5 只动物进行分析。所有组在 1 小时后，动态顺应性和 PaO2/吸入氧分数比至少降低 50%。虽然所有模型中的顺应性仍然降低，但在冲洗组中，5 小时后氧合恢复到基线值。高潮气量模型中的弥漫性肺泡损伤更严重，与对照和冲洗动物之间没有差异。在吸入和大潮气量模型中，支气管肺泡灌洗液中的白细胞介素-6 增加。
尽管所有模型都达到了符合急性呼吸窘迫综合征标准的相似生理效应，但肺损伤模型之间的生物学反应有所不同。酸吸入模型产生了通常在 ALI 中观察到的呼吸和炎症反应；这些数据表明，它可能是研究大鼠呼吸机相关性肺损伤中期影响的最具临床适用性的模型。
