Muellenbach Ralf M, Kredel Markus, Zollhoefer Bernd, Johannes Amelie, Kuestermann Julian, Schuster Frank, Schwemmer Ulrich, Wurmb Thomas, Wunder Christian, Roewer Norbert, Brederlau Jörg
Department of Anesthesiology, University of Wuerzburg, Germany. muellenbac
Exp Lung Res. 2009 Apr;35(3):222-33. doi: 10.1080/01902140802534975.
Surfactant depletion is most often used to study acute respiratory failure in animal models. Because model stability is often criticized, the authors tested the following hypotheses: Repeated pulmonary lavage with normal saline provides stable experimental conditions for 24 hours with a PaO2/FiO2 ratio < 300 mm Hg. Lung injury was induced by bilateral pulmonary lavages in 8 female pigs (51.5 +/- 4.8 kg). The animals were ventilated for 24 hours (PEEP: 5 cm H2O; tidal volume: 6 mL/kg; respiratory rate: 30/min). After 24 hours the animals were euthanized. For histopathology slides from all pulmonary lobes were obtained. Supernatant of the bronchoalveolar fluid collected before induction of acute respiratory distress syndrome (ARDS) and after 24 hours was analyzed. A total of 19 +/- 6 lavages were needed to induce ARDS. PaO2/FiO2 ratio and pulmonary shunt fraction remained significantly deteriorated compared to baseline values after 24 hours (P < .01). Slight to moderate histopathologic changes were detected. Significant increases of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were observed after 24 hours (P < .01). The presented surfactant depletion-based lung injury model was associated with increased pulmonary inflammation and fulfilled the criteria of acute ling injury (ALI) for 24 hours.
表面活性剂耗竭常用于研究动物模型中的急性呼吸衰竭。由于模型稳定性常受诟病,作者检验了以下假设:用生理盐水反复进行肺灌洗可在24小时内提供稳定的实验条件,使动脉血氧分压/吸入氧分数(PaO2/FiO2)比值<300 mmHg。对8只雌性猪(51.5±4.8 kg)进行双侧肺灌洗以诱导肺损伤。动物通气24小时(呼气末正压:5 cm H2O;潮气量:6 mL/kg;呼吸频率:30次/分钟)。24小时后对动物实施安乐死。获取所有肺叶的组织病理学切片。分析急性呼吸窘迫综合征(ARDS)诱导前和24小时后收集的支气管肺泡灌洗液的上清液。诱导ARDS总共需要进行19±6次灌洗。与基线值相比,24小时后PaO2/FiO2比值和肺分流分数仍显著恶化(P<.01)。检测到轻微至中度的组织病理学变化。24小时后观察到肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6显著增加(P<.01)。所呈现的基于表面活性剂耗竭的肺损伤模型与肺部炎症增加相关,并在24小时内符合急性肺损伤(ALI)的标准。