Functional and morphological assessment of early impairment of airway function in a rat model of emphysema.

The aim of this study was to evaluate airway structure-function relations in elastase-induced emphysema in rats. Sprague-Dawley rats were treated intratracheally with 50 IU porcine pancreatic elastase (PPE, n = 8) or saline (controls, n = 6). Six weeks later, lung volumes [functional residual capacity (FRC), residual volume (RV), and total lung capacity (TLC)] and low-frequency impedance parameters (Newtonian resistance, R(N); tissue damping; tissue elastance, H) were measured, and tracheal sounds were recorded during slow inflation to TLC following in vivo degassing. The lungs were fixed and stained for standard morphometry, elastin, and collagen. In the PPE group, FRC and RV were higher [4.53 ± 0.7 (SD) vs. 3.28 ± 0.45 ml; P = 0.003 and 1.06 ± 0.35 vs. 0.69 ± 0.18 ml; P = 0.036, respectively], and H was smaller in the PPE-treated rats than in the controls (1,344 ± 216 vs. 2,178 ± 305 cmH(2)O/l; P < 0.001), whereas there was no difference in R(N). The average number of crackles per inflation was similar in the two groups; however, the crackle size distributions were different and the lower knee of the pressure-volume curves was higher in the PPE group. Microscopic images revealed different alveolar size distributions but similar bronchial diameters in the two groups. The treatment caused a slight but significant decrease in the numbers of alveolar attachments, no difference in elastin and slightly increased mean level and heterogeneity of collagen in the bronchial walls. These results suggest that tissue destruction did not affect the conventionally assessed airway resistance in this emphysema model, whereas the alterations in the recruitment dynamics can be an early manifestation of impaired airway function.

[1]  J. Sallenave,et al.  Local lung responses following endobronchial elastase and lipopolysaccharide instillation in sheep , 2006, International journal of chronic obstructive pulmonary disease.

[2]  B Suki,et al.  Wave propagation, input impedance, and wall mechanics of the calf trachea from 16 to 1,600 Hz. , 1993, Journal of applied physiology.

[3]  H. Stanley,et al.  Scaling behavior in crackle sound during lung inflation , 1999, Proceedings of the First Joint BMES/EMBS Conference. 1999 IEEE Engineering in Medicine and Biology 21st Annual Conference and the 1999 Annual Fall Meeting of the Biomedical Engineering Society (Cat. N.

[4]  Minoru Yoshida,et al.  A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats. , 2002, American journal of respiratory and critical care medicine.

[5]  A. M. Houghton,et al.  Epithelial cell apoptosis causes acute lung injury masquerading as emphysema. , 2009, American journal of respiratory cell and molecular biology.

[6]  J. Fredberg,et al.  Mechanical impedance of the lung periphery. , 1997, Journal of applied physiology.

[7]  Robert B. Darling,et al.  Effects of low work function metals on the barrier height of sulfide‐treated n‐type GaAs(100) , 1992 .

[8]  M. Cosio,et al.  Animal models of chronic obstructive pulmonary disease. , 2008, American journal of physiology. Lung cellular and molecular physiology.

[9]  J. Hohlfeld,et al.  Elastase-induced lung emphysema in rats is not reduced by hematopoietic growth factors when applied preventionally , 2008, Virchows Archiv.

[10]  Z. Hantos,et al.  Plethysmographic estimation of thoracic gas volume in apneic mice. , 2006, Journal of applied physiology.

[11]  J. H. Comroe,et al.  A rapid plethysmographic method for measuring thoracic gas volume: a comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects. , 1956, The Journal of clinical investigation.

[12]  K. Lutchen,et al.  Tissue heterogeneity in the mouse lung: effects of elastase treatment. , 2004, Journal of applied physiology.

[13]  M. Cosio,et al.  Behavior of morphometric indices in pancreatic elastase-induced emphysema in rats , 2007, Lung.

[14]  K. Lutchen,et al.  Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling. , 2005, Journal of applied physiology.

[15]  D. Gaver,et al.  Interaction between airway lining fluid forces and parenchymal tethering during pulmonary airway reopening. , 1995, Journal of applied physiology.

[16]  J. Fredberg,et al.  Input impedance and peripheral inhomogeneity of dog lungs. , 1992, Journal of applied physiology.

[17]  R. Brown,et al.  A method of endotracheal intubation and pulmonary functional assessment for repeated studies in mice. , 1999, Journal of applied physiology.

[18]  I. Uchiyama,et al.  An emphysema model in rats treated intratracheally with elastase. , 1987, Environmental research.

[19]  H. Eugene Stanley,et al.  Mathematical Modeling of the First Inflation of Degassed Lungs , 1998, Annals of Biomedical Engineering.

[20]  Arnab Majumdar,et al.  Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment. , 2003, Journal of applied physiology.

[21]  B Suki,et al.  Lung volumes and respiratory mechanics in elastase-induced emphysema in mice. , 2008, Journal of applied physiology.

[22]  D. Gaver,et al.  Effects of surface tension and viscosity on airway reopening. , 1990, Journal of applied physiology.

[23]  A MODIFICATION OF THE FORCED OSCILLATION TECHNIQUE , 1981 .

[24]  R. Rizi,et al.  Regional correlation of emphysematous changes in lung function and structure: a comparison between pulmonary function testing and hyperpolarized MRI metrics. , 2011, Journal of applied physiology.

[25]  D. Hyde,et al.  Pulmonary vagal reflexes and breathing pattern are not altered in elastase-induced emphysema in rats. , 1997, Experimental lung research.

[26]  G. Snider,et al.  Remodeling of alveolar walls after elastase treatment of hamsters. Results of elastin and collagen mRNA in situ hybridization. , 1998, American journal of respiratory and critical care medicine.

[27]  W M Thurlbeck,et al.  Aspects of chronic airflow obstruction. , 1977, Chest.

[28]  B. Celli Pathophysiology of chronic obstructive pulmonary disease. , 1998, Respiratory care clinics of North America.

[29]  P. Macklem,et al.  Effects of elastase-induced emphysema on airway responsiveness to methacholine in rats. , 1989, Journal of applied physiology.

[30]  Z. Hantos,et al.  Crackle-sound recording to monitor airway closure and recruitment in ventilated pigs , 2006, European Respiratory Journal.

[31]  Arnab Majumdar,et al.  Quantitative characterization of airspace enlargement in emphysema. , 2006, Journal of applied physiology.