Measurement of bronchoconstriction using whole-body plethysmograph: comparison of freely moving versus restrained guinea pigs.

We have previously measured pulmonary function in guinea pigs using a double-chambered plethysmograph, however, the question remains regarding the accuracy of the double-chamber to gauge the long-term pulmonary function of late asthmatic response. This may be affected by confounding factors, such as stress on the animal and differences in size of the collar around the neck. Therefore, in this study we compared histamine-induced bronchoconstriction in the same guinea pigs using a single- versus a double-chambered body box. In the double-chambered body box, the specific airway resistance is proportional to time delay between thoracic and nasal flows and measured in cmH2O x s. Whereas, in the single-chambered body box, PenH units (Enhanced Pause) reflect "effort of breathing." This is measured as the pause between inspiration and expiration. Doubling concentrations of histamine (12.5-200 microg/ml dissolved in normal saline) were administered by DeVilbiss nebulizer for 1 min, followed by 1 min suction of residual drug in the chamber, and then the airway resistance was recorded by the computer for the following 3 min. There was a 15-min wash-out period between two doses of histamine. There was no statistically significant difference (p > 0.05) in the PC100 values for histamine between the two methods, however, it was much easier to work with the single-chambered body box in terms of handling the animal and eliminating the possible influence of collar placement on the bronchoconstriction. In conclusion, the data suggests histamine challenges produce equivalent PC100 data in both the double-chambered plethysmograph with sRAW units and single-chambered plethysmograph using the PenH units.

An in vivo model of beta-adrenoceptor desensitization.

Chronic use of beta2-agonists and increased production of inflammatory mediators during the late allergic reaction after antigen challenge results in the desensitization of beta-adrenoceptors in the airways and the accompanying rise in nonspecific airway hyperresponsiveness. In this study, we established an in vivo model of beta2-adrenoceptor desensitization in guinea pig airways by administration of IL-1beta intratracheally or chronic albuterol by inhalation. In the establishment of beta-adrenoceptor desensitization in response to both beta-agonist or inflammatory mediator, baseline pulmonary function responses were established to methacholine and isoproterenol-induced relaxation of methacholine bronchoconstriction. This was followed by the administration of IL-1beta (500 IU/d intratracheally for 2 days) or chronic albuterol (0.1 g/L by aerosol for 1 min three times a day for 10 days). After administration, the methacholine and isoproterenol-methacholine response was once again evaluated. Intratracheal administration of IL-1beta or chronic administration of albuterol significantly decreased (p < 0.05) the protective effect of isoproterenol on methacholine-induced bronchoconstriction, eliciting beta-adrenoceptor desensitization in vivo. The in vivo model will be very useful in monitoring the effect of other potential drugs on beta-adrenoceptor function in the airways.