The ability to treat preterm infants with respiratory problems has significantly improved with the advent of infant intensive care units, advanced monitoring systems, and new mechanical ventilation techniques. Although a large number of these neonates recover uneventfully, many of those who require prolonged mechanical ventilation are difficult to wean from the ventilator, demonstrate radiologic evidence of acquired tracheomegaly, and develop chronic respiratory problems. Specifically, growth and development of the respiratory system are significantly jeopardized by predisposing factors associated with immaturity. In contrast to the extensive body of knowledge on the neonatal lung, little physiological data are available concerning airway function and the role of airway smooth muscle activity. The understanding of basic airway function at early stages of development has been impeded by the lack of an appropriate in vivo experimental animal model. Recent advancements in liquid ventilation techniques have demonstrated that the immature lamb, as young as 106 days of gestation, can be studied independent of the umbilical-placental circulation in an extrauterine environment. The proposed research will utilize this model to characterize the basic functional properties of an isolated segment of lamb airway and to quantitate any alteration in these properties induced by airway smooth muscle activity and/or mechanical stresses associated with positive pressure ventilation. In addition, experiments are planned which will investigate the possible role of smooth muscle tone in preventing pressure induced airway deformation of the immature lung. This research should provide a further understanding of basic biological development which can facilitate the continual advancement of neonatal clinical management.
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