MATURATION AFFECTS THE MAXIMAL PULMONARY RESPONSE TO METHACHOLINE IN RABBITS

Maximal bronchoconstriction in normal adults produces only small reductions in pulmonary function; however, in normal infants severe airway obstruction limits testing to low agonist concentrations. In this study, maximal pulmonary response to methacholine was evaluated in 5 immature (1 month old) and 5 mature (6 months old) rabbits. Animals were anesthetized, paralyzed, and mechanically ventilated via a tracheostomy tube. Changes in pulmonary function were assessed from maximal deflation flow volume curves following inhalation of doubling concentrations of methacholine between 0.6 and 320 mg/mL. Following 320 mg/mL methacholine, the immature rabbits had a greater percent decline in forced vital capacity (FVC) than the mature animals (55 +/- 15% vs. 36 +/- 10%; P < 0.05). At 50% FVC, isovolume flows were measurable in the 5 mature rabbits, and 4 of 5 had plateaus in their dose-response curves. At the higher methacholine doses, only 1 of 5 immature animals had measurable isovolume flows because of the decrease in FVC. There was no significant difference between immature and mature animals in the methacholine dose required to decrease baseline flows by 50%. We conclude that in rabbits maturation affects maximal pulmonary response but not the sensitivity to methacholine. (C) 1993 Wiley-Liss, Inc.