Skip to main content
SpringerLink
Log in

Assessing Structure–Function Relations in Mice Using the Forced Oscillation Technique and Quantitative Histology

  • Protocol
  • First Online:
Alpha-1 Antitrypsin Deficiency

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1639))

Abstract

The structure and function of the lung gradually becomes compromised during the progression of emphysema. In this chapter, we first describe how to assess and evaluate lung function using the forced oscillation technique. Next, we provide details on how to use the Flexivent system to measure respiratory mechanical parameters in mice. We also describe the outlines of how to set up a homemade forced oscillatory system and use it to measure respiratory mechanics. To characterize the structure from standard histological images, we describe a method that is highly sensitive to early emphysema. Correlating structural information such as equivalent alveolar diameter and its variance with respiratory elastance or compliance, provides structure–function relationships that can subsequently reveal novel mechanisms of emphysema progression or be used to track the effectiveness of treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Snider G, Kleinerman J, Thurlbeck W, Bengali Z (1985) The definition of emphysema. Report of a national heart, lung, and blood institute, division of lung diseases workshop. Am Rev Respir Dis 132:182–185

    Google Scholar 

  2. Stockley RA, Mannino D, Barnes PJ (2009) Burden and pathogenesis of chronic obstructive pulmonary disease. Proc Am Thorac Soc 6(6):524–526. doi:10.1513/pats.200904-016DS. 6/6/524 [pii]

    Article  CAS  PubMed  Google Scholar 

  3. Tuder RM, McGrath S, Neptune E (2003) The pathobiological mechanisms of emphysema models: what do they have in common? Pulm Pharmacol Ther 16(2):67–78

    Article  CAS  PubMed  Google Scholar 

  4. Celli BR, MacNee W, Agusti A, Anzueto A, Berg B, Buist AS, Calverley PMA, Chavannes N, Dillard T, Fahy B, Fein A, Heffner J, Lareau S, Meek P, Martinez F, McNicholas W, Muris J, Austegard E, Pauwels R, Rennard S, Rossi A, Siafakas N, Tiep B, Vestbo J, Wouters E, ZuWallack R (2004) Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J 23:932–946. doi:10.1183/09031936.04.00014304

    Article  CAS  PubMed  Google Scholar 

  5. Girod CE, King TEJ (2005) COPD: a dust-induced disease? Chest 128:3055–3064. doi:10.1378/chest.128.4.3055

    Article  PubMed  Google Scholar 

  6. Pauwels RA, Rabe KF (2004) Burden and clinical features of chronic obstructive pulmonary disease (COPD). Lancet 364:613–620. doi:10.1016/S0140-6736(04)16855-4

    Article  PubMed  Google Scholar 

  7. Tsuji T, Aoshiba K, Nagai A (2006) Alveolar cell senescence in patients with pulmonary emphysema. Am J Respir Crit Care Med 174:886–893. doi:10.1164/rccm.200509-1374OC

    Article  CAS  PubMed  Google Scholar 

  8. Bishai JM, Mitzner W (2008) Effect of severe calorie restriction on the lung in two strains of mice. Am J Physiol Lung Cell Mol Physiol 295:L356–L362. doi:10.1152/ajplung.00514.2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Karlinsky JB, Goldstein RH, Ojserkis B, Snider GL (1986) Lung mechanics and connective tissue levels in starvation-induced emphysema in hamsters. Am J Phys 251:R282–R288

    CAS  Google Scholar 

  10. Ganrot PO, Laurell CB, Eriksson S (1967) Obstructive lung disease and trypsin inhibitors in alpha-1-antitrypsin deficiency. Scand J Clin Lab Invest 19:205–208

    Article  CAS  PubMed  Google Scholar 

  11. Kononov S, Brewer K, Sakai H, Cavalcante FS, Sabayanagam CR, Ingenito EP, Suki B (2001) Roles of mechanical forces and collagen failure in the development of elastase-induced emphysema. Am J Respir Crit Care Med 164(10 Pt 1):1920–1926

    Article  CAS  PubMed  Google Scholar 

  12. Suki B, Lutchen KR, Ingenito EP (2003) On the progressive nature of emphysema: roles of proteases, inflammation, and mechanical forces. Am J Respir Crit Care Med 168(5):516–521

    Article  PubMed  Google Scholar 

  13. Parameswaran H, Majumdar A, Suki B (2011) Linking microscopic spatial patterns of tissue destruction in emphysema to macroscopic decline in stiffness using a 3D computational model. PLoS Comput Biol 7(4):e1001125. doi:10.1371/journal.pcbi.1001125. ARTN e1001125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bates JH, Irvin CG, Farre R, Hantos Z (2011) Oscillation mechanics of the respiratory system. Compr Physiol 1(3):1233–1272. doi:10.1002/cphy.c100058

    PubMed  Google Scholar 

  15. Hantos Z, Daroczy B, Suki B, Nagy S, Fredberg JJ (1992) Input impedance and peripheral inhomogeneity of dog lungs. J Appl Physiol 72(1):168–178

    Article  CAS  PubMed  Google Scholar 

  16. Brewer KK, Sakai H, Alencar AM, Majumdar A, Arold SP, Lutchen KR, Ingenito EP, Suki B (2003) Lung and alveolar wall elastic and hysteretic behavior in rats: effects of in vivo elastase treatment. J Appl Physiol 95(5):1926–1936

    Article  PubMed  Google Scholar 

  17. Hamakawa H, Bartolak-Suki E, Parameswaran H, Majumdar A, Lutchen KR, Suki B (2011) Structure-function relations in an elastase-induced mouse model of emphysema. Am J Respir Cell Mol Biol. doi:10.1165/rcmb.2010-0473OC. 2010-0473OC [pii]

    PubMed  Google Scholar 

  18. Sato S, Bartolak-Suki E, Parameswaran H, Hamakawa H, Suki B (2015) Scale dependence of structure-function relationship in the emphysematous mouse lung. Front Physiol 6:146. doi:10.3389/fphys.2015.00146

    PubMed  PubMed Central  Google Scholar 

  19. Dunnill M (1962) Quantitative methods in the study of pulmonary pathology. Thorax 17:320–328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Weibel ER, Gomez DM (1962) A principle for counting tissue structures on random sections. J Appl Physiol 17:343–348

    CAS  PubMed  Google Scholar 

  21. Mazzolo A, Bt R, Gille W (2003) Properties of chord length distributions of nonconvex bodies. J Math Phys 44:6195

    Article  Google Scholar 

  22. Santaló L (1976) Integral geometry and geometric probability. Addison-Wesley Publishing Company, Inc, London

    Google Scholar 

  23. Parameswaran H, Majumdar A, Ito S, Alencar AM, Suki B (2006) Quantitative characterization of airspace enlargement in emphysema. J Appl Physiol 100(1):186–193

    Article  PubMed  Google Scholar 

  24. Saetta M, Shiner RJ, Angus GE, Kim WD, Wang NS, King M, Ghezzo H, Cosio MG (1985) Destructive index: a measurement of lung parenchymal destruction in smokers. Am Rev Respir Dis 131:764–769

    CAS  PubMed  Google Scholar 

  25. Thurlbeck WM (1967) Internal surface area and other measurements in emphysema. Thorax 22:483–496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Emami K, Cadman RV, Woodburn JM, Fischer MC, Kadlecek SJ, Zhu J, Pickup S, Guyer RA, Law M, Vahdat V, Friscia ME, Ishii M, Yu J, Gefter WB, Shrager JB, Rizi RR (2008) Early changes of lung function and structure in an elastase model of emphysema–a hyperpolarized 3He MRI study. J Appl Physiol 104:773–786. doi:10.1152/japplphysiol.00482.2007

    Article  PubMed  Google Scholar 

  27. Gillooly M, Lamb D (1993) Microscopic emphysema in relation to age and smoking habit. Thorax 48:491–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Saetta M, Kim WD, Izquierdo JL, Ghezzo H, Cosio MG (1994) Extent of centrilobular and panacinar emphysema in smokers' lungs: pathological and mechanical implications. Eur Respir J 7:664–671

    Article  CAS  PubMed  Google Scholar 

  29. Ito S, Bartolak-Suki E, Shipley JM, Parameswaran H, Majumdar A, Suki B (2006) Early emphysema in the tight skin and pallid mice: roles of microfibril-associated glycoproteins, collagen, and mechanical forces. Am J Respir Cell Mol Biol 34(6):688–694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Suki B, Lutchen KR (1992) Pseudorandom signals to estimate apparent transfer and coherence functions of nonlinear systems: applications to respiratory mechanics. IEEE Trans Biomed Eng 39(11):1142–1151

    Article  CAS  PubMed  Google Scholar 

  31. Farre R, Rotger M, Navajas D (1992) Optimized estimation of respiratory impedance by signal averaging in the time domain. J Appl Physiol 73(3):1181–1189

    CAS  PubMed  Google Scholar 

  32. Ito S, Ingenito EP, Arold SP, Parameswaran H, Tgavalekos NT, Lutchen KR, Suki B (2004) Tissue heterogeneity in the mouse lung: effects of elastase treatment. J Appl Physiol 97(1):204–212

    Article  CAS  PubMed  Google Scholar 

  33. Ito S, Lutchen KR, Suki B (2007) Effects of heterogeneities on the partitioning of airway and tissue properties in normal mice. J Appl Physiol 102(3):859–869. doi:10.1152/japplphysiol.00884.2006. 00884.2006 [pii]

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

B. Suki was supported by the National Institutes of Health Grants HL-111745 and H. Parameswaran was supported by HL129468.

Author information

Authors and Affiliations

  1. Northeastern University College of Bioengineering, Boston, MA, USA

    Harikrishnan Parameswaran

  2. Department of Biomedical Engineering, Boston University, Boston, MA, USA

    Béla Suki

Authors
  1. Harikrishnan Parameswaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Béla Suki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Béla Suki .

Editor information

Editors and Affiliations

  1. Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Florie Borel

  2. Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Christian Mueller

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this protocol

Cite this protocol

Parameswaran, H., Suki, B. (2017). Assessing Structure–Function Relations in Mice Using the Forced Oscillation Technique and Quantitative Histology. In: Borel, F., Mueller, C. (eds) Alpha-1 Antitrypsin Deficiency . Methods in Molecular Biology, vol 1639. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7163-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7163-3_8

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7161-9

  • Online ISBN: 978-1-4939-7163-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation