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INNOVATIVE METHODOLOGIES

Breath-by-breath measurement of particle deposition in the lung of spontaneously breathing rats

¹Institute of Lung Biology and Disease, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; and ; ²Molecular and Integrative Physiological Sciences, Harvard School of Public Health, Boston, Massachusetts

Submitted 30 January 2009 ; accepted in final form 27 July 2009

A number of deposition models for humans, as well as experimental animals, have been described. However, no breath-by-breath deposition measurement in rats has been reported to date. The objective of this study is to determine lung deposition of micrometer-sized particles as a function of breathing parameters in the adult rat lung. A new aerosol photometry system was designed to measure deposition of nonhygroscopic, 2-µm sebacate particles in anesthetized, intubated, and spontaneously breathing 90-day-old Wistar-Kyoto rats placed in a size-adjusted body plethysmograph box. Instrumental dead space of the system was minimized down to 310 µl (i.e., 20% of respiratory dead space). The system allows continuous monitoring of particle concentration in the respired volume. Breathing parameters, such as respiratory rate (f), tidal volume (VT), as well as inspiration/expiration times, were also monitored at different levels of anesthesia. The results showed that VT typically varied between 1.5 and 4.0 ml for regular breathing and between 4.0 and 10.0 ml for single-sigh breaths; f ranged from 40 to 200 breaths/min. Corresponding deposition values varied between 5 and 50%, depending on breath-by-breath breathing patterns. The best fit of deposition (D) was achieved by a bilinear function of VT and f and found to be D = 11.0 – 0.09·f + 3.75·VT. We conclude that our approach provides more realistic conditions for the measurement of deposition than conventional models using ventilated animals and allows us to analyze the correlation between breath-specific deposition and spontaneous breathing patterns.

deposition model; aerosol photometry; rodents; dead space