Maximal airway response in mature and immature rabbits during tidal ventilation

Airway closure during maximal methacholine (MCh) challenge was evaluated using alveolar capsules in eight immature and eight mature anesthetized rabbits in vivo during imposed tidal ventilation. Changes in airway opening and alveolar pressures (delta PA) and pulmonary resistance (RL) were measured during MCh challenge at a positive end-expiratory pressure of 5 cmH2O. In immature rabbits, delta PA remained > 3 cmH2O in all animals, indicating no detectable airway closure. This contrasts to our previous study of isolated immature rabbit lungs under static conditions in which delta PA was < 0.1 cmH2O during maximal MCh challenge, findings consistent with airway closure. Airway closure also did not occur in mature animals during tidal ventilation in vivo; however, the frequency of closure in isolated lungs under static conditions was very low. With increasing MCh, end-expiratory PA increased in immature but not in mature rabbits. RL did not reach a plateau in immature rabbits during MCh, whereas a plateau was reached in mature rabbits. Immature rabbits also had greater increases in RL. These results suggest that tidal ventilation can limit bronchoconstriction in immature rabbits and prevent airway closure during maximal MCh challenge. Tidal ventilation may limit bronchoconstriction by inhibitory effects of stretch on airway smooth muscle contraction and also by causing hyperinflation and thereby increasing transpulmonary pressure.