Journal
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Volume 303, Issue 7, Pages L567-L574Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00217.2012
Keywords
AECOPD; mechanical stress; exacerbation; irreversibility
Categories
Funding
- National Heart, Lung, and Blood Institute [HL-090757, HL-098976]
- Hungarian Scientific Research Fund grant (OTKA) [66700]
- Rosztoczy Foundation
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Szabari MV, Parameswaran H, Sato S, Hantos Z, Bartolak-Suki E, Suki B. Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema. Am J Physiol Lung Cell Mol Physiol 303: L567-L574, 2012. First published August 1, 2012; doi:10.1152/ajplung.00217.2012.-The relation between the progression of chronic obstructive pulmonary disease (COPD) and exacerbations is unclear. Currently, no animal model of acute exacerbation of COPD (AECOPD) exists. The objectives of this study were to evaluate the effects of mechanical forces induced by deep inspirations (DIs) on short-term deterioration of lung structure and function to mimic AECOPD. At 2, 7, or 21 days after treatment with elastase, mice were ventilated with or without DIs (35 cmH(2)O airway pressure for 3 s, 2 times/min) for 1 h. Functional residual capacity (FRC) was measured with body plethysmography, and respiratory compliance, resistance, and hysteresivity were obtained via forced oscillations. From hematoxylin and eosin-stained sections, equivalent airspace diameters (D), alveolar wall thickness (W-t), number of septal ruptures (N-sr), and attachment density (A(d)) around airways were determined. FRC, compliance, and hysteresivity statistically significantly increased with time, and both increased due to DIs. Interestingly, DIs also had an effect on FRC, compliance, resistance, and hysteresivity in control mice. The development of emphysema statistically significantly increased D and W-t in time, and the DIs caused subtle differences in D. At 21 days, the application of DIs changed the distribution of D, increased W-t and N-sr, and decreased A(d). These results suggest that once a critical remodeling of the parenchyma has been reached, acute mechanical forces lead to irreversible changes in structure and function, mimicking COPD exacerbations. Thus, the acute application of DIs in mice with emphysema may serve as a useful model of AECOPD.
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