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Articles in PresS, published online ahead of print February 1, 2002
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00373.2001
Submitted on September 19, 2001
Accepted on January 22, 2002
1 Central Technologies, Novartis Pharma AG, Basel, Switzerland
2 Novartis Horsham Research Centre, Horsham, United Kingdom
3 Respiratory Diseases Therapeutic Area, Novartis Pharma AG, Basel, Switzerland
* To whom correspondence should be addressed. E-mail: nicolau.beckmann{at}pharma.novartis.com.
Using magnetic resonance imaging (MRI), a signal was detected in the lungs of Brown Norway rats following intra-tracheal administration of endotoxin (lipopolysaccharide; LPS). The signal had two components: one, of diffuse appearance and higher intensity, was particularly prominent up to 48 h following LPS; the second, showing an irregular appearance and weaker intensity, was predominant later. Broncho-alveolar lavage fluid analysis indicated that generalized granulocytic (especially neutrophilic) inflammation was a major contributor to the signal at the early time points, with mucus being a major factor contributing at the later time points. The fact that animals can breathe freely during data acquisition and that neither respiration nor cardiac triggering is applied renders this MRI approach attractive for the routine testing of anti-inflammatory drugs. In particular, the prospect of non-invasively detecting a sustained mucus hypersecretory phenotype in the lung brings an important new perspective to models of chronic obstructive pulmonary diseases in animals.
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