Germann P G, Häfner D
Institute of Pathology and Toxicology, Byk Gulden, Hamburg, Germany.
J Pharmacol Toxicol Methods. 1998 Aug;40(2):101-7. doi: 10.1016/s1056-8719(98)00048-3.
The time course of histopathological changes in a rat lung lavage model of the acute respiratory distress syndrome (ARDS) was analyzed by sacrificing animals 10, 30, 60, 180, and 210 min after the last lung parenchyma lavage which was performed with physiological saline solution. This lavage depleted the lung from its natural surfactant resources leading into a pathophysiological cascade similar to that of the acute respiratory distress syndrome. Tracheotomized rats (12 animals per time point) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration-expiration ratio of 1:2, peak inspiratory pressure of 28 cm H2O at positive end-expiratory pressure (PEEP) of 8 cm H2O. During the whole experimental period, the ventilation was not changed. Blood gases (partial arterial oxygen pressures [PaO2, mmHg] and partial arterial carbon dioxide pressures [PaCO2, mmHg]) were estimated before, directly after, and 10, 30, 60, 90, 120, 150, 180, and 210 min after the last lavage. For grading lung lavage-induced histopathological changes associated with the time-dependent development of ARDS, slides were coded and evaluated without any knowledge of the sacrifice time. A semiquantitative grading was performed with respect to the severity of the following parameters: hyaline membrane formation (HM), interstitial and intraalveolar edema edema (E), and margination and infiltration of polymorphonuclear neutrophil leukocytes (PMNL) into the lung alveoli. The severity of these parameters showed a time-dependent increase after the last lavage. This was accompanied by a time-dependent decrease in partial arterial oxygen pressure (PaO2) values during the early postlavage period (up to 30 min). Thereafter, PaO2 levels remained fairly stable. The severity of intraalveolar and/or perivascular hemorrhages within the lung was not time dependent. The rat lavage model shows similarities to the pathophysiological sequelae occuring during the acute phase of the acute respiratory distress syndrome in humans. Most of the characteristic pathognomic histological changes seen in humans can be observed in this lung lavage model. This ARDS model is brief and easy in its experimental design, showed a good and homogeneous reproducibility of pathophysiological and histopathological parameters, and is therefore a useful model to estimate the influence of therapeutic pharmacological treatments of ARDS.
在急性呼吸窘迫综合征（ARDS）大鼠肺灌洗模型中，于末次用生理盐水进行肺实质灌洗后10、30、60、180和210分钟处死动物，分析组织病理学变化的时间进程。此次灌洗耗尽了肺内天然表面活性物质资源，引发了类似于急性呼吸窘迫综合征的病理生理级联反应。对气管切开的大鼠（每个时间点12只动物）使用西门子Servo Ventilator 900C进行压力控制通气，吸入100%氧气，呼吸频率为30次/分钟，吸呼比为1:2，在呼气末正压（PEEP）为8 cm H2O时，吸气峰压为28 cm H2O。在整个实验期间，通气情况保持不变。在末次灌洗前、灌洗后即刻以及灌洗后10、30、60、90、120、150、180和210分钟测定血气（动脉血氧分压[PaO2，mmHg]和动脉血二氧化碳分压[PaCO2，mmHg]）。为了对与ARDS时间依赖性发展相关的肺灌洗诱导的组织病理学变化进行分级，对切片进行编码并在不知道处死时间的情况下进行评估。针对以下参数的严重程度进行半定量分级：透明膜形成（HM）、间质和肺泡内水肿（E）以及多形核中性粒细胞（PMNL）向肺泡的边缘化和浸润。这些参数的严重程度在末次灌洗后呈时间依赖性增加。这伴随着灌洗后早期（至30分钟）动脉血氧分压（PaO2）值的时间依赖性下降。此后，PaO2水平保持相当稳定。肺内肺泡内和/或血管周围出血的严重程度不具有时间依赖性。大鼠灌洗模型与人类急性呼吸窘迫综合征急性期发生的病理生理后果相似。在该肺灌洗模型中可以观察到人类中出现的大多数特征性病理组织学变化。这个ARDS模型的实验设计简单且耗时短，在病理生理和组织病理学参数方面具有良好且均匀的可重复性，因此是评估ARDS治疗性药物治疗影响的有用模型。
