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Decreased pulmonary vasoreactivity in an animal model of chronic Pseudomonas pneumonia
L M Graham1, A Vasil, M L Vasil
1Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Abstract:
Chronic pulmonary infection/colonization caused by Pseudomonas aeruginosa accounts for much of the morbidity and mortality in cystic fibrosis (CF). The effect of chronic pulmonary P. aeruginosa infection on the pulmonary circulation has not been studied. Therefore, we investigated the effect of chronic P. aeruginosa infection on pulmonary hemodynamics in a rat model. Two groups of rats were inoculated with either agar beads containing 1.0 x 10(4) colony-forming units of P. aeruginosa (infected) or an equal volume of sterile beads alone (control). In vivo, pulmonary vasoreactivity measured as the percent change in total pulmonary resistance during hypoxia was decreased at 1 wk (22 +/- 7% versus 57 +/- 3%), 2 wk (29 +/- 5% versus 73 +/- 17%), 3 wk (41 +/- 8% versus 77 +/- 14%), and 6 to 9 wk (23 +/- 10 versus 53 +/- 7; p less than 0.05 all time points; mean +/- SEM) postinoculation in infected animals when compared with that in time-matched control animals. At 6 to 9 wk postinoculation, pulmonary artery pressure was significantly elevated in infected rats (25.8 +/- 1.6 versus 21.0 +/- 1.0 mm Hg; p less than 0.05) when compared with that in control animals. Histopathologic findings were characterized by bronchiectasis as well as by chronic bronchial, parenchymal, and perivascular inflammation at all time points in infected animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF) impairs pulmonary vasoreactivity and increases pulmonary artery pressure. This study reveals significant hemodynamic changes in a rat model of CF lung infection.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Cardiovascular Physiology
Background:
- Pseudomonas aeruginosa chronic pulmonary infections are a major cause of morbidity and mortality in cystic fibrosis (CF).
- The impact of chronic P. aeruginosa infection on pulmonary circulation in CF has not been previously investigated.
Purpose of the Study:
- To investigate the effects of chronic P. aeruginosa infection on pulmonary hemodynamics in a rat model.
Main Methods:
- Rats were inoculated with P. aeruginosa-containing agar beads (infected) or sterile beads (control).
- Pulmonary vasoreactivity was measured during hypoxia.
- Pulmonary artery pressure was assessed at 6-9 weeks post-inoculation.
- Histopathological analysis was performed.
Main Results:
- Pulmonary vasoreactivity was significantly decreased in infected rats at 1, 2, 3, and 6-9 weeks post-inoculation compared to controls.
- Pulmonary artery pressure was significantly elevated in infected rats at 6-9 weeks.
- Histopathology revealed bronchiectasis and chronic inflammation in infected animals.
Conclusions:
- Chronic P. aeruginosa infection in this rat model leads to impaired pulmonary vasoreactivity and pulmonary hypertension.
- These findings suggest a significant impact of P. aeruginosa lung infection on pulmonary hemodynamics in CF.