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Published ahead of print on December 11, 2003, doi:10.1164/rccm.200307-949OC
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American Journal of Respiratory and Critical Care Medicine Vol 169. pp. 679-686, (2004)
© 2004 American Thoracic Society


Original Article

Preferential Diaphragmatic Weakness during Sustained Pseudomonas aeruginosa Lung Infection

Maziar Divangahi, Stefan Matecki, Roy W. R. Dudley, Stephanie A. Tuck, Weisheng Bao, Danuta Radzioch, Alain S. Comtois and Basil J. Petrof

Respiratory Division and Meakins-Christie Laboratories, McGill University Health Centre; and Centre for Host Resistance, McGill University Health Centre Research Institute, Montreal, Quebec, Canada

Correspondence and requests for reprints should be addressed to Basil J. Petrof, M.D., Respiratory Division, Room L411, Royal Victoria Hospital, 687 Pine Avenue West, Montreal, PQ, H3A 1A1 Canada. E-mail: basil.petrof{at}mcgill.ca

Infection with Pseudomonas aeruginosa plays a major role in the pulmonary inflammation and injury associated with cystic fibrosis. Lung inflammation may also lead to more widespread systemic effects on other organs. We tested the following hypotheses: (1) ongoing P. aeruginosa lung infection produces diaphragmatic and limb muscle weakness and (2) such muscle dysfunction is directly correlated with the level of pulmonary inflammation. Chronic bronchopulmonary infection with mucoid P. aeruginosa was induced in C57BL/6 mice. At Day 2 after infection, diaphragmatic force was decreased (37%) only in mice infected with a high dose of 1 x 106 cfu, whereas by Day 7 after infection, diaphragmatic force was similarly reduced (36%) even at a fivefold lower inoculating dose. No significant correlations were found between diaphragmatic weakness and pulmonary inflammation, as assessed by the number of neutrophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid. Moreover, in marked contrast to the diaphragm, no effects of P. aeruginosa infection on contractile function were observed in prototypical slow- and fast-twitch hindlimb muscles. We conclude that sustained lung infection with P. aeruginosa induces preferential weakness of the diaphragm, which is not directly correlated with the degree of pulmonary inflammation induced under these conditions.

Key Words: respiratory muscles • sepsis • cystic fibrosis • lung inflammation • chronic Pseudomonas pneumonia




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