A rat model of acute respiratory distress syndrome (ARDS): Part 1. Time dependency of histological and pathological changes

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 deplete d the lung from its natural surfactant resources leading into a pathophysio logical cascade similar to that of the acute respiratory distress syndrome. Tracheotomized rats (12 animals per time point) were pressure-controlled v entilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths/min, inspiration-expiration ratio of 1.2, peak inspirat ory pressure of 28 cm H2O at positive end-expiratory pressure (PEEP) of 8 c m H2O. During the whole experimental period, the ventilation was not change d. Blood gases (partial arterial oxygen pressures [PaO2 mmHg] and partial a rterial carbon dioxide pressures [PaCO2 mmHg]) were estimated before, direc tly after, and 10, 30, 60, 90, 120, 150, 180, and 210 min after the last la vage. For grading lung lavage-induced histopathological changes associated with t he time-dependent development of ARDS, slides were coded and evaluated with out any knowledge of the sacrifice time. A semiquantitative grading was per formed with respect to the severity of the following parameters: hyaline me mbrane formation (HM), interstitial and intraalveolar edema edema (E), and margination and infiltration of polymorphonuclear neutrophil leukocytes (PM NL) into the lung alveoli. The severity of these parameters showed a time-d ependent increase after the last lavage. This was accompanied by a time-dep endent decrease in partial arterial oxygen pressure (PaO2) values during th e early postlavage period (up to 30 min). Thereafter, PaO2 levels remained fairly stable. The severity of intraalveolar and/or perivascular hemorrhage s within the lung was not time dependent. The rat lavage model shows simila rities to the pathophysiological sequelae occuring during the acute phase o f the acute respiratory distress syndrome in humans. Most of the characteri stic pathognomic histological changes seen in humans can be observed in thi s 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 estim ate the influence of therapeutic pharmacological treatments of ARDS. (C) 19 99 Elsevier Science Inc.