Intratracheal Instillation Versus Intratracheal Inhalation of Tracer Particles for Measuring Lung Clearance Function
- 1 January 1997
- journal article
- research article
- Published by Taylor & Francis in Experimental Lung Research
- Vol. 23 (1), 17-34
- https://doi.org/10.3109/01902149709046045
Abstract
Effective elimination of particles deposited in the respiratory tract is an important defense function to protect the organism from potentially adverse effects of inhaled particles. Delivery of radioactively labeled tracer particles and subsequent measurement in vivo of their retention in different regions of the respiratory tract provides an adequate method for characterizing this defensive function. However, the delivery of such tracer particles by inhalation may result in some external contamination of the animals and requires specific protective measures while working with radioactive aerosols. In this study, 85Sr-labeled tracer particles (3 microns) were administered to the lower respiratory tract of rats by intratracheal inhalation to avoid external contamination, and also by intratracheal instillation in order to compare the 2 technique with respect to their suitability for measuring normal and impaired particle clearance rates. It was postulated that particle clearance function in the alveolar region can be determined equally well with intratracheally instilled particles despite their uneven distribution in the lung. For both techniques, rats were anesthesized with halothane and the particles were administered via oral intubation. Retention in the lower respiratory tract of about 30 micrograms (inhalation) and 6 micrograms (instillation) of the administered particles was followed over a period of 180 days by external counting of lung 85Sr-activity in a collimated detection system. To impair alveolar particle clearance rates, groups of rats were subjected to 12 weeks of inhalation exposure prior to delivery of the tracer particles as follows: (1) sham-exposed control; (2) pigment-grade TiO2 particles to induce lung overload: (3) ultrafine TiO2 particles: (4) crystalline SiO2 particles (cristobalite). The following results were obtained: The long-term retention half-times (T1/2) of the tracer particles reflecting alveolar clearance consistently showed the same ranking of the treatment groups whether measured after intratracheal inhalation or instillation. Control values were 66 and 72 days, respectively, and significantly prolonged long-term clearance was measured by both methods for pigment-grade TiO2 (117 and 99 days), ultrafine TiO2 (541 and 600 days) and SiO2 (1901 and 1368 days). Comparison of these values between the two modes of administration of tracer particles showed no significant differences. In contrast, the short-term T1/2 (mucociliary clearance) of the intratracheally instilled tracer particles in the different treatment groups were variable and did not accurately reflect particle clearance from the conducting airways. However, short-term T1/2 after intratracheal inhalation of tracer particles were consistent with fast conducting airway clearance, and mucociliary clearance appears to be stimulated when alveolar clearance is significantly impaired due to particle overload or to effects of cytotoxic particles. The results suggest that intratracheal instillation of a low dose (< or = 10 micrograms) of tracer particles in the rat provides an adequate method for reliably determining effects of inhaled toxicants on alveolar particle clearance function. Further, intratracheal inhalation of tracer particles is useful for measuring both short-term (mucociliary) and long-term (alveolar) particle clearance rates in the lower respiratory tract of the rat.Keywords
This publication has 23 references indexed in Scilit:
- Heterogeneity of Phagocytosis for Inhaled versus Instilled MaterialAmerican Review of Respiratory Disease, 1992
- Role of the Alveolar Macrophage in Lung Injury: Studies with Ultrafine ParticlesEnvironmental Health Perspectives, 1992
- Alveolar Macrophages in a Particle "Overload" ConditionJournal of Aerosol Medicine, 1990
- Establishing aerosol exposure concentrations for inhalation toxicity studiesToxicology and Applied Pharmacology, 1989
- Lung Clearance of Inhaled Insoluble and Soluble ParticlesJournal of Aerosol Medicine, 1988
- Regional Deposition of Inhaled Monodisperse Coarse and Fine Aerosol Particles in Small Laboratory AnimalsAnnals of Work Exposures and Health, 1988
- Measurement of the deposition and clearance of inhaled radiolabeled particles from rat lungsJournal of Applied Toxicology, 1986
- Clearance from the respiratory tract*1Fundamental and Applied Toxicology, 1985
- Retention of microspheres in the rat lung after intratracheal instillationEnvironmental Research, 1981
- Pulmonary distribution of particles given by intratracheal instillation or by aerosol inhalationEnvironmental Research, 1976