Oleic Acid Induced Acute Lung Injury/Acute Respiratory Distress Syndrome Animal Model

The experiments were performed to investigate the oleic acid induced changes in lung variables for the measure of ALI, inflammatory mediators and to test the hypothesis that intravenous administration of oleic acid in the rat may serve as a relevant model to study human ALI/ARDS so as to assess various formulations in the treatment of syndrome.

Two groups each containing 48 animals were used in this study: (a) Control group, i.e., animals receiving 0.1% bovine serum albumin only; (b) animals receiving 300 μl of an OA suspension immediately after vortexing (50 μl of pure OA suspended in 250 μl of 0.1 percent BSA). After set periods of time (4, 8, 24 and 30 h) group of 12 animals per time point were sacrificed to assess respiratory functions.

Intravenous Oleic acid instillation resulted in severe pulmonary inflammation with peak changes noted at 24 h with resolution seen by the end of 30 h. Plethysmograph readings demonstrated increasing tachypnoea with highest RR of 135 breaths per minute at 24 h as compared to control group indicating a progression of the disease process (p < 0.05). Also a significant decline in tidal volume was seen (p < 0.01) noted at the end of 24 h. Bronchoalveolar lavage fluid analysis demonstrated inflammatory changes consisting of increased neutrophil count, TLC and total protein content. The cytokine levels in BALF measured after induction with OA revealed significantly increased levels of IL-1β, IL-6 and TNF-α in comparison with control group (p < 0.001). Lung wet/dry weight ratio increased significantly as compared to control group at 4, 8 and 24 h (p < 0.01).

OA animal model of fat embolism-induced ARDS represents one of the various diseases that make up the syndrome of ARDS and can be used to evaluate various formulations in the treatment of ARDS.