An automatic video instillator for intratracheal instillation in the rat

Abstract

Intratracheal instillation (ITI) of a test compound is an alternative method to inhalation methods that require complex aerosol generation, exposure chambers and airflow monitoring instruments for exposing the lungs of animals to a test compound. For ITI in the rat, a laryngoscope is generally used for endotracheal intubation, and the procedure is difficult to perform. Therefore, we designed and constructed an automatic video instillator (AVI) for the accurate delivery of a dose of a test compound into the trachea of rats. The device has a videocamera probe for image guidance, and a liquid-crystal display for image display. These two items are used to visualize the larynx and trachea for intratracheal insertion of the tubing, and for placing the tip of the instillation tubing beyond the vocal cords for ITI of the test compound. After a 2 h training session on the use of the AVI in an anaesthetized rat, we assessed the utility of the device by ITI of 0.25% (w/v) solution of Evans Blue dye into the lungs of 30 isoflurane-anaesthetized rats. Necropsy examinations were performed on 20 rats immediately after the completion of the procedure, and on 10 rats three days after the procedure. Based on the results of these examinations, we concluded that the device could be used for rapid, reproducible and successful ITI of a test compound into the lungs of a rat by one operator. The pulmonary toxicology of environmental toxins to assess their physicochemical characteristics, such as the effect of particle size and distribution, and the biological response that follows their exposure in humans is studied frequently by either inhalation or intratracheal instillation (ITI) of the toxin in rodents.1 For pulmonary toxicity studies, specialized equipment that includes aerosol generators, airflow monitoring instruments, exposure chambers, exhaust systems and often analytical chemical support is required in order to deliver known amounts of the test compound into the lungs. Consequently, the need for this equipment increases the cost and technical complexity of such studies.2 ITI has become a feasible alternative method for delivering a toxin into the lung of rodents, 3 -6 because the required equipment is less sophisticated than that required for inhalation toxicity studies. 7 -9 This method is also simpler and safer than the inhalation method: many dose levels of compounds with a wide range of physicochemical properties and toxicity can be introduced rapidly into the lungs with minimal risk to the operator. Furthermore, ITI is used often as a screen to determine an appropriate dose range for inhalation toxicity studies. Despite the advantages of ITI over inhalation, the use of ITI for the pulmonary toxicology studies in rodents does have limitations.10 One such limitation is the resultant pulmonary distribution of the toxin. In inhalation studies, the distribution of the test compound in the right and left lungs is uniform, whereas it is non-uniform when using ITI. In addition, Lakatos et al. suggested that oropharynge...

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