Mechanism of thiopental-induced constriction of guinea pig trachea

The authors studied the effects of thiopental on baseline airway tone in intact guinea pig tracheas using a preparation where the epithelial (inside) and serosal (outside) surfaces were isolated. Whole tracheas were excised, cannulated, and mounted in 50-ml tissue baths. The serosal and epithelial surfaces were perfused via separate circuits with Krebs-Henseleit solution. All data were expressed as a percent of constriction produced by 2 x 10^-6 M carbachol (a concentration that elicited a 90 + % of maximal constriction). Thiopental elicited a dose-dependent constriction in all 25 tracheas. Increases in tone were first seen at 10^-5 M (14.3 ± 1.84%; mean ± SEM) and reached a peak at 10^-3 M (29 ± 3.16%; P < .0001). Responses to thiopental were similar when the epithelium was removed, when thiopental was added to the inner perfusate, and when tracheas were pretreated with 10^-5 M pyrilamine. Constriction was entirely inhibited by pretreatment with indomethacin 10^-5 M. The authors conclude that thiopental, at concentrations in the clinical range, causes a reproducible dose-dependent constriction of guinea pig trachea. This effect is mediated by constrictor prostaglandins.