Measuring the lung function in the mouse: the challenge of size

Abstract

Measurement of the effects of drugs, mediators and infectious agents on various models of lung disease, as well as assessment of lung function in the intact mouse has the potential for significantly advancing our knowledge of lung disease. However, the small size of the mouse presents significant challenges for the assessment of lung function. Because of compromises made between precision and noninvasiveness, data obtained may have an uncertain bearing on the mechanical response of the lung. Nevertheless, considerable recent progress has been made in developing valid and useful measures of mouse lung function. These advances, resulting in our current ability to measure sophisticated indices of lung function in laboratory animals, are likely to lead to important insights into the mechanisms of lung disease.

Figure 1

Photomicrograph of the parenchyma and respiratory bronchioles of a mouse (20 gram female BALB/c) lung. Note the rapid branching from a conducting airway into alveolar ducts and the relatively large airways. Stain is H & E with 5 × magnification.

Figure 2

Two common and basic mechanical models of the lung. A: A homogeneously ventilated model consisting of a single elastic balloon (elastance E) served by a single flow-resistive pipe (resistance R). B: A homogeneous model again with a single airway (resistance R₁), but with a Kelvin body consisting of two springs (E₁ and E₂) and a dashpot (resistance R₂) to account for the viscoelastic behavior of the lung tissue.

Figure 3

The non-invasiveness-precision continuum of the phenotyping uncertainty principle – see text for discussion.

Figure 4

Pulmonary impedance measurements in anesthetized mice. The diagram shows airway opening pressure plotted against time. Volume and flow excursions for each breath are maintained constant by use of a volume-cycled ventilator. Increases in the magnitude of lung impedance following acethycholine injection are assessed as the increase in pressure above baseline. Note the increased responsiveness in the A/J compared the C3He/J strain of mouse. APTI: Airway pressure time index. Used with permission [38].

Figure 5

The respiratory input impedance of the mouse. Open squares represent baseline conditions while closed circles show the result of administering an aerosol of methacholine. The solid and dashed lines are the fit provided by the constant-phase model (Eq. 6). Used with permission [17].

Figure 6

The mechanical response of the mouse lung to methacholine in terms of the parameters of the constant-phase model (see Eq. 6 in text). The open squares correspond to control BALB/c mice, while the closed circles represent mice sensitized to and challenged with ovalbumin. Taken from [17] with permission.