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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
Bruno Tigani1, Catherine Cannet1, Harry Karmouty Quintana1,3, Fran=E7ois-
Xavier Bl=E91,2,4, Stefan Zurbruegg1, Elisabeth Schaeublin2, John R.
Fozard2, Nicolau Beckmann1,
1Discovery Technologies and 2Respiratory Diseases Research Department,
Novartis Institutes for BioMedical Research, CH-4002 Basel,
Switzerland;
3 Sackler Institute of Pulmonary Pharmacology, King's College London,
London SE1 1UL
4 Faculty of Pharmacy, University Louis Pasteur-Strasbourg-I, F-67401
Illkirch, France.
Correspondence and reprint requests to: Nicolau Beckmann, PhD Novartis
Institutes for BioMedical Research, Discovery Technologies, Analytics
and Imaging Sciences Unit
Lichtstr. 35; WSJ-386.2.09 CH-4002 Basel Switzerland e-mail:
nicolau.beckmann@[EMAIL PROTECTED]
+41-61-3249576, fax: +41-61-3243889
More Information:
http://www.novartiskills.eu
A.L.F. Crime Investigation Agency (CIA)
alfcia_vries@[EMAIL PROTECTED]
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