End-expiratory and tidal volumes measured in conscious mice using single projection x-ray images

Abstract

The evaluation of airway resistance (Raw) in conscious mice requires both end-expiratory (Ve) and tidal volumes (Vt) (Lai-Fook SJ and Lai YL. J Appl Physiol 98: 2204–2218, 2005). In anesthetized BALB/c mice we measured lung area (AL) from ventral-to-dorsal x-ray images taken at FRC (Ve) and after air inflation with 0.25 and 0.50 ml (ΔVL). Total lung volume (VL) described by equation: VL = ΔVL + VFRC = KAL1.5 assumed uniform (isotropic) inflation. Total VFRC averaged 0.55 ml, consisting of 0.10 ml tissue, 0.21 ml blood and 0.24 ml air. K averaged 1.84. In conscious mice in a sealed box, we measured the peak-to-peak box pressure excursions (ΔPb) and x-rays during several cycles. K was used to convert measured AL1.5 to VL values. We calculated Ve and Vt from the plot of VL vs. cos(α − φ). Phase angle α was the minimum point of the Pb cycle to the x-ray exposure. Phase difference between the Pb and VL cycles (φ) was measured from ΔPb values using both room- and body-temperature humidified box air. A similar analysis was used after aerosol exposures to bronchoconstrictor methacholine (Mch), except that φ depended also on increased Raw. In conscious mice, Ve (0.24 ml) doubled after Mch (50–125 mg/ml) aerosol exposure with constant Vt, frequency (f), ΔPb, and Raw. In anesthetized mice, in addition to an increased Ve, repeated 100 mg/ml Mch exposures increased both ΔPb and Raw and decreased f to apnea in 10 min. Thus conscious mice adapted to Mch by limiting Raw, while anesthesia resulted in airway closure followed by diaphragm fatigue and failure.