1Infectious Diseases Department, Maharashtra University of Health Sciences, Seth GSMC & KEM Hospital, Mumbai 400012
2Bombay Veterinary College, Mumbai
3National Chair, Clinical Pharmacology, Indian Council of Medical Research, New Delhi
*Corresponding Author E-mail: teju113@gmail.com
Online published on 29 May, 2014.
Despite of advances in therapy and overall medical care, ALI/ARDS mortality remains high. There is a need to develop animal model which mimics ALI/ARDS in humans, so as to evaluate new treatment modalities.
To develop rat model of ALI/ARDS using Intratracheal Lipopolysaccharide.
Two groups of Wistar Rats, 36 per group were treated with (a) Intratracheal (IT) Lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS) (b) control group: IT NS. After set periods of time (4, 8 and 24 h) groups of 6 animals per time point were sacrificed to assess respiratory functions. At each time interval, 2 animals were subjected to chest X-rays. Plethysmograph readings were taken for all the animals. Bronchoalveolar lavage fluid (BALF) collection was done in 6 animals. Left lung wet/dry weight ratio and histopathological examination was performed on right lungs for 6 animals after sacrificing them.
Intratracheal LPS instillation resulted in acute severe pulmonary inflammation with peak changes noted at 8 h with resolution seen by the end of 24 h. Plethysmograph readings demonstrated increasing tachypnoea with respiratory distress at 8 h as compared to control group indicating a progression of the disease process (p < 0.01). Also a significant decline in tidal volume was seen (p < 0.05) noted at the end of 8 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 LPS 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 and 8 h (p < 0.01).
Intratracheal instillation of LPS in the rat showed functional, cytological and histological changes in the lungs with peak changes noted after 8 h of induction, comparable to those observed in ALI/ARDS patients. Hence this model can be used to evaluate various new formulations in the treatment of ALI/ARDS.
Acute Lung Injury, Acute Respiratory Distress Syndrome, Lipopolysaccharide, Endotoxemia, Septicemia
