Alveolar fractal box dimension inversely correlates with mean linear intercept in mice with elastase-induced emphysema

Mary P. Andersen, A. Read Parham, J. Clifford Waldrep, Wayland N. McKenzie, Rajiv Dhand

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Rationale: A widely applicable model of emphysema that allows efficient and sensitive quantification of injury is needed to compare potential therapies. Objectives: To establish such a model, we studied the relationship between elastase dose and the severity of emphysema in female C57BL/6J mice. We compared alveolar fractal box dimension (DB), a new measure which is an assessment of the complexity of the tissue, with mean linear intercept (Lm), which is commonly used to estimate airspace size, for sensitivity and efficiency of measurement. Methods: Emphysema was induced in female C57BL/6J mice by administering increasing intratracheal doses of porcine pancreatic elastase (PPE). Changes in morphology and static lung compliance (CL) were examined 21 days later. Correlation of DB with Lm was determined in histological sections of lungs exposed to PPE. The inverse relationship between DB and Lm was supported by examining similar morphological sections from another experiment where the development of emphysema was studied 1 to 3 weeks after instillation of human neutrophil elastase (HNE). Results: Lm increased with PPE dose in a sigmoidal curve. CL increased after 80 or 120 U/kg body weight (P < 0.05), but not after 40 U/kg, compared with the control. DB progressively declined from 1.66 ± 0.002 (standard error of the mean) in controls, to 1.47 ± 0.006 after 120 U PPE/kg (P < 0.0001). After PPE or HNE instillation, DB was inversely related to Lm (R = -0.95, P < 0.0001 and R = -0.84, P = 0.01, respectively), with a more negative slope of the relationship using HNE (P < 0.0001). Conclusion: Intratracheal instillation of increasing doses of PPE yields a scale of progression from mild to severe emphysema. DB correlates inversely with Lm after instillation of either PPE or HNE and yields a rapid, sensitive measure of emphysema after elastase instillation.

Original languageEnglish (US)
Pages (from-to)235-243
Number of pages9
JournalInternational Journal of COPD
Volume7
DOIs
StatePublished - May 2 2012

Fingerprint

Fractals
Pancreatic Elastase
Emphysema
Swine
Leukocyte Elastase
Inbred C57BL Mouse
Lung Compliance
Compliance
Body Weight
Lung

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Health Policy
  • Public Health, Environmental and Occupational Health

Cite this

Alveolar fractal box dimension inversely correlates with mean linear intercept in mice with elastase-induced emphysema. / Andersen, Mary P.; Read Parham, A.; Clifford Waldrep, J.; McKenzie, Wayland N.; Dhand, Rajiv.

In: International Journal of COPD, Vol. 7, 02.05.2012, p. 235-243.

Research output: Contribution to journalArticle

Andersen, Mary P. ; Read Parham, A. ; Clifford Waldrep, J. ; McKenzie, Wayland N. ; Dhand, Rajiv. / Alveolar fractal box dimension inversely correlates with mean linear intercept in mice with elastase-induced emphysema. In: International Journal of COPD. 2012 ; Vol. 7. pp. 235-243.
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