Characterization of oleic acid-induced acute respiratory distress syndrome model in rat

Abstract

Animal studies using oleic acid (OA) model to produce acute respiratory distress syndrome (ARDS) have been inconsistent. Therefore, the present study was undertaken to establish an acute model of ARDS in rats using OA and to characterize its effect on cardio-respiratory parameters and lethality. The trachea, jugular vein and femoral artery of anesthetized adult rats were cannulated. A dose of OA (30-90 µL; iv) was injected in each animal and changes in respiratory frequency (RF), heart rate (HR) and mean arterial pressure (MAP) were recorded. Minute ventilation and PaO₂/FiO₂ (P/F)ratio were also determined. At the end, lungs were excised for determination of pulmonary water content and histological examination. At all doses of OA, there was immediate decrease followed by increase in RF, however at 75 and 90 µL of OA, RF decreased abruptly and the animals died by 63 ± 8.2 min and 19 ± 6.3 min; respectively. In all the groups, HR and MAP changes followed the respiratory changes. The minute ventilation increased in a dose-dependent manner while the values of P/F ratio decreased correspondingly. Pulmonary edema was induced at all doses. Histological examination of the lung showed alveolar damage, microvascular congestion, microvascular injury, infiltration of inflammatory cells, pulmonary edema and necrosis in a dose-dependent manner. With these results, OA can be used to induce different grades of ARDS in rats and OA doses of 50, 60 and 75 µL resemble mild, moderate and severe forms of ARDS respectively. Hence, OA model serves as a useful tool to study the pathophysiology of ARDS.