Lung volumes and respiratory mechanics in elastase-induced emphysema in mice

Hantos, Zoltán; Adamicza, A.; Jánosi, Tibor Z.; Szabari, Margit V.; Tolnai, József; Suki, Bélâ

doi:10.1152/japplphysiol.90924.2008

Cited by 53 publications

(49 citation statements)

References 51 publications

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“…1) including FRC, compliance, and hysteresivity increased with time due to the development of emphysema following PPE treatment as in previous studies (11,16,27). The resistance decreased with time as in the tight-skin mouse (15); however, this is in contrast to observed changes in airway resistance in human COPD patients (43).…”

Section: Discussionmentioning

confidence: 56%

Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema

Szabari

Parameswaran

Sato

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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. 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.00217.2012The 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 2O 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 (Ad) 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 Wt in time, and the DIs caused subtle differences in D. At 21 days, the application of DIs changed the distribution of D, increased Wt and Nsr, and decreased Ad. 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. AECOPD; mechanical stress; exacerbation; irreversibility CHRONIC OBSTRUCTIVE PULMONARY disease (COPD), including chronic bronchitis and emphysema, is a slowly developing and progressive disease with episodes of acute exacerbation (AE-COPD). According to the latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) Summary (8a), AECOPD is an acute event characterized by a worsening of the patient's respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication. Most AECOPD is triggered by bacterial (36) or viral (35) infections, by pollutants (33), or by cold temperature (4). Moreover, severe exacerbation-related hospitalization is associated with an increased risk of mortality, even after discharge (8), with a heavy health care burden worldwide.While the frequency of AECOPD was shown to correlate with lung function decline (5, 34), irreversible structural changes behind the functional decline following AECOPD have been identified only recently. Tanabe et al. (38) reported that changes in the distribution of low-attenuation areas on computerized tomography images of COPD patients were consistent with the coalescence...

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Section: Discussionmentioning

confidence: 56%

Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema

Szabari

Parameswaran

Sato

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Another advantage is that the fast development of structural destruction allows us to investigate the detailed time course of the progression. Furthermore, the elastase-injury model has been shown to produce airspace enlargement and increases in lung volumes and compliance similar to those in human patients (31). Thus, this model should be adequate for a first-order evaluation of structure-function relations during disease progression.…”

Section: Discussionmentioning

confidence: 90%

Structure–Function Relations in an Elastase-Induced Mouse Model of Emphysema

Hamakawa

Bartolák‐Suki

Parameswaran

et al. 2011

Am J Respir Cell Mol Biol

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Emphysema is a progressive disease characterized by the destruction of peripheral airspaces and subsequent decline in lung function. However, the relation between structure and function during disease progression is not well understood. The objective of this study was to assess the time course of the structural, mechanical, and remodeling properties of the lung in mice after elastolytic injury. At 2, 7, and 21 days after treatment with porcine pancreatic elastase, respiratory impedance, the constituents of lung extracellular matrix, and histological sections of the lung were evaluated. In the control group, no changes were observed in the structural or functional properties, whereas, in the treatment group, the respiratory compliance and its variability significantly increased by Day 21 (P , 0.001), and the difference in parameters decreased with increasing positive end-expiratory pressure. The heterogeneity of airspace structure gradually increased over time. Conversely, the relative amounts of elastin and type I collagen exhibited a peak (P , 0.01) at Day 2, but returned to baseline levels by Day 21. Structure-function relations manifested themselves in strong correlations between compliance parameters and both mean size and heterogeneity of airspace structure (r 2 . 0.9). Similar relations were also obtained in a network model of the parenchyma in which destruction was based on the notion that mechanical forces contribute to alveolar wall rupture. We conclude that, in a mouse model of emphysema, progressive decline in lung function is sensitive to the development of airspace heterogeneity governed by local, mechanical, forceinduced failure of remodeled collagen.

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“…This is in accord with our findings in mice (Study 3, [3]). The knee in the P−V curve was shifted statistically significantly to higher P rs in the treated rats, which was in contrast with the observations in mice (Study 3, [3]). …”

Section: Crackles and Airway Structure/function In Emphysematous Ratssupporting

confidence: 94%

“…17). The amplitude distribution of the crackle 39 sounds followed a power law, in agreement with previous studies in normal dog lungs [5] and in PPE-treated mice (Study 3, [3]). …”

Section: Crackles and Airway Structure/function In Emphysematous Ratssupporting

confidence: 91%

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Crackle sounds and lung recruitment

Tolnai

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Lung volumes and respiratory mechanics in elastase-induced emphysema in mice

Cited by 53 publications

References 51 publications

Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema

Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema

Structure–Function Relations in an Elastase-Induced Mouse Model of Emphysema

Crackle sounds and lung recruitment

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