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

Abstract

. Airway resistance due to alveolar gas compression measured by barometric plethysmography in mice. J Appl Physiol 98: 2204 -2218, 2005. First published January 27, 2005 doi:10.1152/japplphysiol.00869.2004.-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 ϭ A btVb/[Vt (Ve ϩ 0.5Vt)]. Here Abt is the area under the box pressuretime curve during inspiration or expiration, V b is box volume, Vt 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 Abt and Vt for temperature-humidity and gas compression effects, respectively, using a sinusoidal analysis. In anesthetized mice, Raw averaged 4.3 cmH 2O ⅐ ml Ϫ1 ⅐ 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 cmH 2O ⅐ ml Ϫ1 ⅐ 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 Raw observed at room temperature. The method using the increase in A bt with bronchoconstriction provides a conservative estimate for the increase in Raw in conscious mice. bronchoconstriction; methacholine; tidal volume; gas conditioning; conscious mice; anesthetized mice AIRWAY RESISTANCE (R aw ) in small animals is used to evaluate the efficacy of pharmacological agents in the treatment of allergic airway disease. In particular, the use of barometric plethysmography with conscious unrestrained mice in a closed box is particularly appealing because of its noninvasiveness and technical simplicity. Drorbaugh and Fenn (7) showed that tidal volume (V t ) is related to excursions in box pressure caused by changes in temperature and humidity of the airflow from the box to the alveolar space. This method for measuring V t has been validated in studies of newborn infants (7), monkeys (12), and mice (22); however, its accuracy has been questioned (9). The measurement of airway responsiveness from the cyclic variations of box pressure (17, 19) has been criticized because of the compounding effects of alveolar gas compression and the effects of temperature and humidity (gas conditioning). Lundblad et al. (17) from experiments in anesthetized mice concluded that the contribu...

Complete inhibition of allergic airway inflammation and remodelling in quadruple IL‐4/5/9/13−/− mice

“…Kumar et al [24], on the other hand, have demonstrated that IL‐13 −/− mice chronically exposed to OVA demonstrate significant reduction in inflammatory cells, sub‐epithelial fibrosis and mucus cell hyperplasia, but still developed AHR. These results with AHR are different from ours, possibly because of the use of the enhanced pause measurement in a body plethysmograph for assessing AHR by Kumar et al [25], a method that may not necessarily reflect changes in lung mechanics. Our results show that knocking out the Th2 cytokine gene cluster prevented allergen‐induced AHR to a similar extent as knocking out only IL‐13, placing IL‐13 as being most crucial for the expression of AHR.…”

Restrained whole body plethysmography for measure of strain-specific and allergen-induced airway responsiveness in conscious mice

“…This could be avoided in future experiments by conducting the entire study without opening the chamber, i.e., aerosolizing agonists to the mice within the chamber using special delivery systems (3,19). Incorporation of heating elements or warmed water (39,40,42) or decreasing the size or thickness of the chamber walls may also serve to stabilize the thermal conditions of the box interior. Alternatively, flow-type plethysmography has been described (49), which would minimize the effects of baseline thermal drift, although pose additional challenges, e.g., maintaining calibration.…”

“…One major concern with the use of an unheated plethysmograph was the potential for errors to arise in the computation of sRaw, from heating and humidification of inspired gas, which has been shown to cause the box pressure amplitude to nearly double (39,40,57). We explored this issue by performing a pilot experiment with conscious mice (BALB/c female, n ϭ 5, 21.6 -27.1 g), whereby sRaw was determined in the heated and humidified (37°C, 90% humidity) vs. unheated (26°C, 66% humidity) box.…”

Reduced hypoxic ventilatory response in newborn mice knocked‐out for the progesterone receptor

“…Whole-body plethysmography remains the best choice to measureV E and frequency of apnoeas in unrestrained and minimally disturbed animals, which was desired in the present study. It has been suggested that determination of V T with this approach cannot discriminate the signal generated by heating and humidification of inspired air (Drorbough & Fenn, 1955;Mortola & Frappell, 1998) and the signal generated by compression of air during inspiration, when airway resistances are elevated (Lai-Fook & Lai, 2005). However, our values for V T of newborn mice [0.5-1 ml (100 g) −1 ] are in the same range as the values obtained with head-out plethysmography recordings (Mortola, 1984;Robinson et al 2000;Bissonnette & Knopp, 2001), a method that directly measures the pressure changes due to inspiration, and they are also consistent with values obtained by acoustic plethysmography in newborn mice (Daubenspeck et al 2008).…”