title: Preferential diaphragmatic weakness during sustained Pseudomonas aeruginosa lung infection.
abstract: 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 10(6) 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.
authors.affiliation: Respiratory Division and Meakins-Christie Laboratories, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Maziar
authors.initials: M
authors.lastname: Divangahi
authors.forename: Stefan
authors.initials: S
authors.lastname: Matecki
authors.forename: Roy W R
authors.initials: RW
authors.lastname: Dudley
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Tuck
authors.forename: Weisheng
authors.initials: W
authors.lastname: Bao
authors.forename: Danuta
authors.initials: D
authors.lastname: Radzioch
authors.forename: Alain S
authors.initials: AS
authors.lastname: Comtois
authors.forename: Basil J
authors.initials: BJ
authors.lastname: Petrof
mesh_terms: D000818:Animals; D015169:Colony Count, Microbial; D003964:Diaphragm / Q000503:physiopathology*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000503:physiopathology; D008168:Lung / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology; D018908:Muscle Weakness / Q000382:microbiology* / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000503:physiopathology*; D018410:Pneumonia, Bacterial / Q000382:microbiology / Q000503:physiopathology; D011552:Pseudomonas Infections / Q000150:complications*; D015656:Respiratory Mechanics / Q000502:physiology; D012141:Respiratory Tract Infections / Q000150:complications*; D013997:Time Factors