Assessment of airway reactivity in guinea pigs: comparison of methods employing whole body plethysmography.

Airway reactivity of guinea pigs was assessed while animals were in whole body plethysmographs by measurement of responses to histamine aerosol. Histamine was delivered using 2 protocols: one employed exposure to a single concentration, the other utilized 1.5-fold stepped concentrations. Both protocols were tested while animals inhaled ambient air, and again when the air contained 10% CO2. Exposures to single concentrations of histamine in air produced increases in both respiratory frequency (f) and plethysmograph pressure (delta P). The latter increase was shown to coincide with a decrease in tidal volume and with the onset of airway constriction. The time to reach a doubling in delta P represented a quantitative measure of airway reactivity. Exposures using the single concentration method in conjunction with 10% CO2 also demonstrated a dose-dependent time to reach the endpoint, in this case a 33% decrease in delta P from the maximum CO2-induced increase. The endpoints for the stepped concentration protocols were the concentration required to double delta P (PC2.delta P) or, in the presence of 10% CO2, the concentration that induced a 33% decline from the maximum delta P (PC33 (CO2]. Mean values for PC2.delta P and PC33 (CO2) were 2.1 mg/m3 and 0.58 mg/m3, respectively. These endpoints were comparable based on the dose received as calculated from the minute volume of animals when breathing the above atmospheres. The intersubject variability, assessed using both stepped concentration protocols, was comparable to that reported for PC20 FEV1 in human studies. Both stepped concentration protocols, conducted in air, or the 10% CO2 atmospheres, proved suitable for determination of airway reactivity of the unrestrained, unanesthetized guinea pigs. However, by not requiring use of CO2, the histamine in air approach is easier to perform, requires less time, and provides a clear endpoint representing early airway constriction.