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J Appl Physiol (May 3, 2002). doi:10.1152/japplphysiol.00080.2002
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Articles in PresS, published online ahead of print May 3, 2002
J Appl Physiol, 10.1152/jap.00080.2002
Submitted on January 31, 2002
Accepted on May 1, 2002

A RE-EVALUATION OF THE VALIDITY OF UNRESTRAINED PLETHYSMOGRAPHY IN MICE

Lennart K.A. Lundblad1, Charles G Irvin2, Andy Adler3, and Jason H Bates2*

1 Vermont Lung Center, University of Vermont, Burlington, VT, USA; Department of Clinical Physiology, Malmo, Lund University, Lund, Sweden
2 Vermont Lung Center, University of Vermont, Burlington, VT, USA
3 AIT Corp, Ottawa, ON, Canada

* To whom correspondence should be addressed. E-mail: jhtbates{at}zoo.uvm.edu.

Currently, unrestrained plethysmography (UP) is widely used to assess bronchial responsiveness in mice. An empirical quantity known as PenH is derived from the plethysmographic box pressure Pb(t) and assumed to be an index of bronchoconstriction. We show that Pb(t) is determined largely by gas conditioning when normal mice breathe spontaneously inside a closed chamber in which the air is at ambient conditions. When the air in the chamber is heated and humidified to body conditions, the changes in Pb(t) are reduced by about two-thirds. The remaining changes are thus due to Boyle's law gas compression and expansion within the lung, and are amplified when the animals breathe through increased resistances. We show that the time-integral of Pb(t) over inspiration is accurately predicted by a term containing airway resistance (Raw), functional residual capacity (FRC) and tidal volume (VT). We conclude that UP can be used to accurately characterise changes in Raw only if FRC and VT are measured independently and the chamber gas is pre-conditioned to body temperature and humidity.




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