Determination of reliable lung function parameters in intubated mice

Respir Res. 2019 Sep 14;20(1):211. doi: 10.1186/s12931-019-1177-9.

Abstract

Background: Animal models and, in particular, mice models, are important tools to investigate the pathogenesis of respiratory diseases and to test potential new therapeutic drugs. Lung function measurement is a key step in such investigation. In mice, it is usually performed using forced oscillation technique (FOT), negative pressure-driven forced expiratory (NPFE) and pressure-volume (PV) curve maneuvers. However, these techniques require a tracheostomy, which therefore only allows end-point measurements. Orotracheal intubation has been reported to be feasible and to give reproducible lung function measurements, but the agreement between intubation and tracheostomy generated-data remains to be tested.

Methods: Using the Flexivent system, we measured lung function parameters (in particular, forced vital capacity (FVC), forced expiratory volume in the first 0.1 s (FEV0.1), compliance (Crs) of the respiratory system, compliance (C) measured using PV loop and an estimate of inspiratory capacity (A)) in healthy intubated BALB/cJ mice and C57BL/6 J mice and compared the results with similar measurements performed in the same mice subsequently tracheostomized after intubation, by means of paired comparison method, correlation and Bland-Altman analysis. The feasibility of repetitive lung function measurements by intubation was also tested.

Results: We identified parameters that are accurately evaluated in intubated animals (i.e., FVC, FEV0.1, Crs, C and A in BALB/cJ and FVC, FEV0.1, and A in C57BL/6 J). Repetitive lung function measurements were obtained in C57BL/6 J mice.

Conclusion: This subset of lung function parameters in orotracheally intubated mice is reliable, thereby allowing relevant longitudinal studies.

Keywords: Asthma; COPD; Lung function; Mice model; Orotracheal intubation.

MeSH terms

  • Air Pressure
  • Animals
  • Asthma / physiopathology
  • Feasibility Studies
  • Forced Expiratory Flow Rates
  • Intubation, Intratracheal*
  • Lung Compliance
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Reproducibility of Results
  • Respiratory Function Tests / standards*
  • Tracheostomy
  • Vital Capacity