A new methodology for controlled particle inhalation by small rodents

In order to investigate the deposition, retention, and clearance mechanisms implicated in particle inhalation under standardized conditions, we develo ped a continuous negative-pressure ventilation system, whereby the breathin g pattern in small rodents could be controlled during exposure to aerosols. Using an on-line open-flow set-up, 19 anesthetized, intubated, and paralyz ed Syrian golden hamsters, individually contained within a whole-body box, were artificially ventilated under the said continuous negative-pressure co nditions, 1 of 5 different combinations of breathing frequency and tidal vo lume being established. The animals were then exposed to aerosols containin g 6-mu m diameter polystyrene spheres, and the deposition of particles in t he conducting airways was monitored photometrically. During exposure, the l evel of respiration (mean lung inflation) was stabilized by means of a nega tive-pressure vent. Breathing frequency and tidal volume, as well as the co mpliance of the system, remained virtually unchanged during the course of a single experiment, and in each case, a reproducible deposition of particle s was achieved. Our findings indicate that tidal volume, but not breathing frequency, has a marked influence on the particle deposition ratio. Breathi ng frequency exerts opposing and counterbalancing effects on this latter pa rameter by enhancing the impaction of particles on the one hand, and by dec reasing sedimentation on the other.