Airway and tissue responses during hyperpnea-induced constriction in guinea pigs

It has been reported that hyperpnea-induced bronchoconstriction in guinea pigs is a potential model for exercise-induced asthma in humans. On the basis of recent studies that show increases in tissue resistance after allergen exposure in sensitized rats, we hypothesized that lung tissues might also be involved in the pathophysiology in this asthma model. We measured tracheal pressure (Ptr) and alveolar pressure (PA) using alveolar capsules in open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 4 cm H2O) guinea pigs under control conditions (regular breathing of warm, humidified air) and after dry gas hyperpnea challenge (HC, mixture of 95% O2 and 5% CO2, 150 breaths/min, 7 min). We calculated lung elastance (EL) and resistance of lung (RL), tissue (Rti), and airway (Raw) by fitting the equation of motion to changes in Ptr and PA. To assess the effects of volume history, we applied a single deep inflation (three times VT) in five HC animals. We performed morphometric analysis in five control and five HC animals, freezing the lungs with liquid nitrogen and processing the tissues via freeze substitution. HC significantly increased RL, Rti, Raw, and EL (424 +/- 62, 771 +/- 230, 287 +/- 33, 259 +/- 31% baseline, respectively). A deep inflation reduced RL, Rti, Raw, and EL by 30 +/- 4, 31 +/- 4, 29 +/- 6, 23 +/- 5%, respectively. In HC animals, the degree of airway constriction was most prominent in the larger airways; extensive tissue distortion was also observed.