Airway resistance due to alveolar gas compression measured by barometric plethysmography in mice

Abstract

We developed a method for measuring airway resistance (Raw) in mice that does not require a measurement of airway flow. An analysis of Raw induced by alveolar gas compression showed the following relationship for an animal breathing spontaneously in a closed box: Raw = AbtVb/[Vt (Ve + 0.5Vt)]. Here Abt is the area under the box pressure-time curve during inspiration or expiration, Vb is box volume, Vt is tidal volume, and Ve is functional residual capacity (FRC). In anesthetized and conscious unrestrained mice, from experiments with both room temperature box air and body temperature humidified box air, the contributions of gas compression to the box pressure amplitude were 15 and 31% of those due to the temperature-humidity difference between box and alveolar gas. We corrected the measured Abt and Vt for temperature-humidity and gas compression effects, respectively, using a sinusoidal analysis. In anesthetized mice, Raw averaged 4.3 cmH2O·ml−1·s, fourfold greater than pulmonary resistance measured by conventional methods. In conscious mice with an assumed FRC equal to that measured in the anesthetized mice, the corrected Raw at room temperature averaged 1.9 cmH2O·ml−1·s. In both conscious mice and anesthetized mice, exposure to aerosolized methacholine with room temperature box air significantly increased Raw by around eightfold. Here we assumed that in the conscious mice both Vt and FRC remained constant. In both conscious and anesthetized mice, body temperature humidified box air reduced the methacholine-induced increase in Raw observed at room temperature. The method using the increase in Abt with bronchoconstriction provides a conservative estimate for the increase in Raw in conscious mice.