AEROALLERGEN-INDUCED DYSPNEA IN FREELY MOVING GUINEA-PIGS - QUANTITATIVE MEASUREMENT BY BIAS FLOW VENTILATED WHOLE-BODY PLETHYSMOGRAPHY

Guinea pigs were sensitized and boostered with i.p. injections of ovalbumin (OA) 10 mug + Al(OH)3 100 mg. Thirteen days after the last injection animals (800-1100 g) were placed in bias flow ventilated whole body plethysmographs and allowed to stabilize for 2 h. Lung function was recorded for up to 2 h before and 5 h after aeroallergen challenge (OA 20 mg/ml, 60 s, 20 psi) by a noninvasive pulmonary analyzer for unrestrained rodents. Aeroallergen challenge produced immediate dyspnea and gasping (peaking between 8 and 17 min). Gasping was associated with an increase in amplitude in the box pressure fluctuations (93%), and in the slope of the fluctuations (391%). Respiratory rate increased (103 to 175 breaths/min, 78%), the product of breathing rate times box pressure amplitude increased (161 to 432, 180%). Relaxation time (the time it takes the box pressure signal to drop from its peak to 1/3 of its peak value) declined (0. 16 to 0.05 s, 72%). All of these lung dysfunction changes were highly significant (p < 0.001). Lung dysfunction persisted for 60 to 120 min after challenge. One of 8 animals tested died within 10 min. None of the animals exhibited late asthmatic responses during the 5 h post-challenge period. Based on these data we conclude that this technique allows quantitative analysis of dyspnea, gasping, and an abnormal pattern (waveform) of breathing. The increase in the slope of the fluctuations, especially at the start of expiration, the concomitant decline in relaxation time, and increased pause time between respiratory cycles appear to be reliable and reproducible markers of early asthmatic responses in the airways of freely moving guinea pigs.