HUMAN AIRWAY SMOOTH-MUSCLE RESPONSIVENESS IN NEONATAL LUNG SPECIMENS

The mechanical activity of proximal airways isolated from human lung s pecimens obtained at autopsy from 11 neonates was studied in response to the following compounds: carbachol, histamine, potassium chloride ( KCl), neurokinin A (NKA) (both in the presence and in the absence of t he neutral endopeptidase inhibitor phosphoramidon) and isoproterenol. Isometric responses to the various concentrations of each of the compo unds were expressed as both raw values of force normalized to smooth m uscle cross-sectional area (SMCSA), i.e., muscle stress and percentage s of the maximal response to acetylcholine. Maximal active muscle stre ss of human neonatal bronchi was induced by carbachol and averaged 95 +/- 25 mN/mm(2) SMCSA (n = 8). The rank of maximal force induced by th e contractile agonists was carbachol > histamine > KCl > NKA, and the rank of the concentration of drug producing one-half of the maximum ef fect (EC(50)) was NKA < carbachol < histamine < KCl. The EC(50) value for isoproterenol was the lowest, although it generated the smallest m echanical response. When compared with results obtained under identica l experimental conditions in the human adult lung, except for carbacho l and isoproterenol, general trends were an increase in force generati on with age and little changes in EC(50) values. There was a decrease in carbachol-induced force with age, whereas the opposite was observed with isoproterenol. We conclude that most of the mechanisms that cont rol airway tone in humans are already present in the neonate. Alterati ons in the response to agonists with the maturational process may have implications in the pharmacologic modulation of bronchial obstruction in neonates.