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Published ahead of print on December 11, 2003, doi:10.1164/rccm.200307-949OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 6, March 2004, 679-686

A more recent version of this article appeared on March 15, 2004
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Submitted on July 23, 2003
Accepted on December 9, 2003

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*

* To whom correspondence should be addressed. 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 post-infection, diaphragmatic force was decreased (37%) only in mice infected with a high dose of 1x106 colony forming units, whereas by day-7 post-infection diaphragmatic force was similarly reduced (36%) even at a 5-fold 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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