Unrestrained plethysmography is an unreliable measure of airways responsiveness in BALB/c and C57BL6 mice

There has been significant utilization of the technique described by Hamelmann et al. (1997) in which a parameter, Penh, related to airways responsiveness is non-invasively measured using unrestrained plethysmography (UP). We investigated this technique, seeking to answer these questions: 1) How do changes in Penh compare with changes in traditional plethysmographic and lung mechanical parameters? 2) How do UP parameters perform in two different mouse strains? Awake immunized and control BALB/c (N=16) and C57BL6 (N=14) mice were placed in the UP chamber and exposed to doses of aerosolized methacholine, while the following parameters were measured at each concentration: inspiratory time (TI), expiratory time (TE), total time (TTot), TI/TTot, peak inspiratory pressure (PI), peak expiratory pressure (PE), Pause, Penh, tidal volume (VT), VT/TI, VT/TE, and VT/TTot. The next day, lung resistance and compliance (RL, CL), were invasively measured in the same animals. For the BALB/c, the parameters with the highest magnitude of correlation coefficient vs. RL are (in order): 1) CL, 2) Pause and Penh, 3) parameters of breathing frequency (TE, TTot, TI) and 4) parameters related to tidal volume (PI, PE, VT). Flow parameters (VT/TTot, VT/TE, VT/TI) and duty cycle parameters (TI/TTot) had insignificant correlations. This ordering is significantly different in the C57BL6, where the parameters with the largest correlations are: 1) CL, 2) parameters of breathing frequency, 3) flow parameters. Pause, Penh, tidal volume and duty cycle parameters had insignificant correlations. This data shows that Penh is problematic in the sense that it is strain specific; it behaves very differently in BALB/c and C57BL6 mice. We suggest that UP parameters largely originate as part of reflex control of breathing processes, rather than in the lung mechanics, and conclude that it is inappropriate to use UP parameters in general, and Penh specifically, as substitute variables for invasive mechanical indices such as RL. Adler, Cieslewicz, Irvin Unrestrained plethysmography and airway responsiveness 3/29