Researchers investigating the genetic component of various disease states r
ely increasingly on murine models. We have developed a ventilator to simpli
fy respiratory research in small animals down to murine size. The new venti
lator provides constant-flow inflation and tidal volume delivery independen
t of respiratory parameter changes. The inclusion of end-inspiratory and en
d-expiratory pauses simplifies the measurement of airway resistance and com
pliance and allows the detection of dynamic hyperinflation (auto-positive e
nd-expiratory pressure). After bench testing, we performed intravenous meth
acholine challenge on two strains of mice (A/J and C57bl/bj) known to diffe
r in their responses by using the new ventilator. Dynamic hyperinflation an
d a decrease in compliance developed during methacholine challenge whenever
respiratory rates of 60-120 breaths/min were employed. In contrast, if dyn
amic hyperinflation was prevented by lengthening expiratory time, (respirat
ory rate = 20 breaths/min), static compliance remained constant. More impor
tantly, the coefficient of variation of the results decreased when lung vol
ume shifts were prevented. In conclusion, airway challenge studies have gre
ater precision when dynamic hyperinflation is prevented.