Dynamic airway constriction in rats: Heterogeneity and response to deep inspiration

Thien Khoi N. Phung, Scott E. Sinclair, Patrudu Makena, Robert C. Molthen, Christopher M. Waters

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Airway narrowing due to hyperresponsiveness severely limits gas exchange in patients with asthma. Imaging studies in humans and animals have shown that bronchoconstriction causes patchy patterns of ventilation defects throughout the lungs, and several computational models have predicted that these regions are due to constriction of smaller airways. However, these imaging approaches are often limited in their ability to capture dynamic changes in small airways, and the patterns of constriction are heterogeneous. To directly investigate regional variations in airway narrowing and the response to deep inspirations (DIs), we utilized tantalum dust and microfocal X-ray imaging of rat lungs to obtain dynamic images of airways in an intact animal model. Airway resistance was simultaneously measured using the flexiVent system. Custom-developed software was used to track changes in airway diameters up to generation 19 (~0.3–3 mm). Changes in diameter during bronchoconstriction were then measured in response to methacholine (MCh) challenge. In contrast with the model predictions, we observed significantly greater percent constriction in larger airways in response to MCh challenge. Although there was a dose-dependent increase in total respiratory resistance with MCh, the percent change in airway diameters was similar for increasing doses. A single DI following MCh caused a significant reduction in resistance but did not cause a significant increase in airway diameters. Multiple DIs did, however, cause significant increases in airway diameters. These measurements allowed us to directly quantify dynamic changes in airways during bronchoconstriction and demonstrated greater constriction in larger airways.

Original languageEnglish
Pages (from-to)L39-L48
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1
StatePublished - Jul 2019

Bibliographical note

Publisher Copyright:
© 2019 the American Physiological Society.


  • Asthma
  • Bronchoconstriction
  • Deep inspiration
  • Methacholine challenge

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


Dive into the research topics of 'Dynamic airway constriction in rats: Heterogeneity and response to deep inspiration'. Together they form a unique fingerprint.

Cite this