INCREASED MAXIMAL PULMONARY RESPONSE TO METHACHOLINE AND AIRWAY SMOOTH-MUSCLE IN IMMATURE COMPARED WITH MATURE RABBITS

We compared the effect of maturation upon the maximal pulmonary respon se to inhaled methacholine in rabbits and also assessed whether there was an age-related difference in the quantity of airway smooth muscle. In sedated, paralyzed, and mechanically ventilated rabbits, pulmonary resistance was measured following increasing doses of aerosolized met hacholine (0.5 to 256 mg/ml). The six mature rabbits (6 mo) demonstrat ed a plateau in their dose-response curves whereas only three of six i mmature animals (1 mo) had a plateau. The immature compared with the m ature animals had a greater maximal increase in pulmonary resistance ( 950% versus 380%). The lungs were examined by light microscopy to dete rmine morphometrically the area of smooth muscle (ASM) in the airway w alls. ASM was normalized for airway size by dividing by the ideal airw ay area. The normalized ASM was different for the two age groups and t he immature animals' airways had more smooth muscle. The relationship between airway size and ASM was similar for the two age groups with sm aller airways having proportionately more smooth muscle. The differenc es with age in ASM area were primarily due to the immature animals hav ing a greater number of airways of small size. There was not a signifi cant relationship between the maximal percent increase in pulmonary re sistance and the normalized ASM. We conclude that inhaled methacholine produces a greater maximal increase in the pulmonary resistance of im mature than mature rabbits and that this difference is unlikely to be caused by a proportionately greater quantity of ASM in the immature th an the mature rabbit airways.