Investigation of effects of anesthesia and age on aspiration in mice through LacZ gene transfer by recombinant E1-deleted adenovirus vectors

To examine the role of disturbed upper airway reflexes in aspiration, we ad ministered 20 mu l of the adenovirus (Ad) vector Ad-CMV-LacZ or 20 mu l of phosphate buffered saline (PBS) intranasally to C57 black mice. We investig ated expression of the LacZ gene by this Ad vector in the nostrils of each mouse, with or without anesthesia. Under anesthesia, LacZ gene expression w as detected in the lungs of every mouse given the Ad vector. However, no La cZ gene expression was found in the trachea or lungs of mice given the Ad v ector without anesthesia. In mice given PBS or wild-type adenovirus transna sally during anesthesia, there was no LacZ gene expression in the nostrils, trachea, or lungs, suggesting that with 5-bromo-4-chloro-3-indolyl-beta-D- galactopyranoside (X-gal) staining, blue-stained cells indicated transferre d LacZ gene expression. These results suggested that aspiration of intranas al solution into lower airways was caused by disturbed upper airway reflexe s during anesthesia. This process can be analyzed by the distribution of La cZ gene expression in airways. We next examined the effect of age on anesth esia-induced aspiration. Twenty-six-mo-old mice exhibited more LacZ gene ex pression in their lungs than did 6-mo-old mice at a concentration of 0.5 to 4.0% halothane in 100% oxygen. This suggests that light anesthesia may dep ress upper airway reflexes and cause aspiration in older animals. This nove l model of aspiration, generated with the Ad-CMV-LacZ vector, may be useful for elucidating the mechanism of development of aspiration pneumonia in re lation to age-related impairment of upper airway reflexes.