Determination of reliable lung function parameters in intubated mice

Eline Bonnardel,Marielle Dubreuil,Renaud Prevel,Isabelle Dupin,Marilyne Campagnac,Patrick Berger,Roger Marthan

doi:10.1186/s12931-019-1177-9

Abstract

BackgroundAnimal 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.MethodsUsing 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.ResultsWe 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.ConclusionThis subset of lung function parameters in orotracheally intubated mice is reliable, thereby allowing relevant longitudinal studies.

Highlights

Animal models and, in particular, mice models, are important tools to investigate the pathogenesis of respiratory diseases and to test potential new therapeutic drugs
Single frequency Forced Oscillation Technique (FOT) measurements fitted to single compartment model allow to only measure resistance (Rrs) and compliance (Crs) of the respiratory system, whereas broadband forced oscillation technique (FOT) measurements fitted to constant phase model distinguish airway and tissue mechanics by quantifying tissue damping (G), tissue elastance (H) and the resistance of the central airways (Rn) [7]
Because the metal cannula used for tracheostomy was traumatic when used for orotracheal intubation, we tested other intubation catheters, and chose the cannula that offered the best compromise between a resistance close to that of the tracheostomy cannula and sufficient flexibility to enable orotracheal intubation

Summary

Introduction

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. It is usually performed using forced oscillation technique (FOT), negative pressure-driven forced expiratory (NPFE) and pressure-volume (PV) curve maneuvers These techniques require a tracheostomy, which only allows end-point measurements. Inflating mouse lungs to a given pressure followed by connection of Bonnardel et al Respiratory Research (2019) 20:211 animal’s airways to a negative pressure reservoir allows to trigger a forced expiratory maneuver and to measure FEV0.1 (forced expiratory volume in the first 0.1 s), FVC (forced vital capacity), and the surrogate of the human FEV1/FVC ratio, so-called FEV0.1/FVC ratio [6]. Lung distensibility (compliance, C, called in some other studies “quasi-static compliance”, Cst) can be characterized by inflating and deflating the lungs with discrete steps to draw a partial pressure-volume (PV) loop [8]

Methods

Results

Discussion

Conclusion