Part 8: Novartis Switzerland: Experiments Killing Rats

The model of repeated low dose allergen challenge has been applied to rats in order to study the major features of chronic airways inflammation. Male rown Norway (BN) rats (Iffa-Credo, L'Arbresle, France) weighing 250-300 g were used. The animals were briefly anaesthetized.
No exposure: Rats were examined by MRI and killed immediately after for histological analysis.
Single exposure: One week after sensitization, animals were given i.t. OA (0.3 mg/kg) or saline (0.2 ml i.t.). These animals were analyzed by MRI 24 h after challenge. They were killed immediately after the MRI session for BAL fluid analysis or histology.
Multiple exposures at 96 h interval: Rats were challenged four times with OA (0.3 mg/kg i.t.) or saline (0.2 ml i.t.), the first challenge taking place one week after sensitization. The procedure adopted for a single exposure was repeated at 96 h, 192 h and 288 h after the first challenge. For each animal MRI images were acquired 6, 24, 48, 96 h after each OA challenge. Animals were killed after the 312 h acquisition (24 h after the fourth challenge) for BAL fluid analysis or histology.

A detailed description of the BAL procedure and the analysis of the parameters of inflammation was provided. Immediately after MRI acquisitions rats were killed by an overdose of pentobarbital (250 mg/kg i.p.). Lungs were fixed by slow in-situ inflation.

Student's t test was also performed using vehicle-treated rats as the control group.

Challenge of actively sensitized BN rats with OA led to an inflammatory response in the airways as assessed by changes in the BAL fluid leukocyte numbers.

Our observations are consistent with other studies performed in guinea pigs, rats and mice.

However, because of respiratory movements, it would be necessary to artificially ventilate and paralyze the rats.


Am J Physiol Lung Cell Mol Physiol (November 3, 2006): Lung inflammation and vascular remodeling after repeated allergen challenge detected noninvasively by MRI