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

¹Center for Biomedical Engineering, University of Kentucky, Lexington, Kentucky and ²Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan

Submitted 10 August 2004 ; accepted in final form 20 January 2005

We developed a method for measuring airway resistance (R_aw) in mice that does not require a measurement of airway flow. An analysis of R_aw induced by alveolar gas compression showed the following relationship for an animal breathing spontaneously in a closed box: R_aw = A_btV_b/[V_t (V_e + 0.5V_t)]. Here A_bt is the area under the box pressure-time curve during inspiration or expiration, V_b is box volume, V_t is tidal volume, and V_e 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 A_bt and V_t for temperature-humidity and gas compression effects, respectively, using a sinusoidal analysis. In anesthetized mice, R_aw 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 R_aw 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 R_aw by around eightfold. Here we assumed that in the conscious mice both V_t and FRC remained constant. In both conscious and anesthetized mice, body temperature humidified box air reduced the methacholine-induced increase in R_aw observed at room temperature. The method using the increase in A_bt with bronchoconstriction provides a conservative estimate for the increase in R_aw in conscious mice.

bronchoconstriction; methacholine; tidal volume; gas conditioning; conscious mice; anesthetized mice

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