Structure-Function of Airway Generations 0 to 4 in the Preterm Lamb

ABSTRACT. Five generations of airways from 15 preterm Premature airways are highly compliant structures compared lambs of 130-137 d (90% term) gestation were studied to with those of the mature newborn or adult (1-4). This increased investigate the effect of generation on structure-function of compliance can cause airway collapse at negative airway pres- preterm airways. Airway rings were measured to determine sures, which results in an increase in resistance to airflow, flow the internal radius (r), and wall thickness (t). The ratio r/t limitation, hyperinflation, poor gas exchange, and ultimately an was then calculated as a morphometric index used in the increased work of breathing (1, 5, 6). The immature airway is determination of wall stress. Airway rings from each gen- especially susceptible to the barotrauma associated with mechan- eration were placed in tissue baths to compare passive, ical ventilation (7-1 1). active, and total force development. Contraction via mem- The decreased compliance seen with maturation may be due brane depolarization (KCl) and muscarinic receptor stim- to changes in the structural and/or functional components of ulation (acetylcholine) were evaluated. As r and t de- the airways. For the trachea, it was demonstrated that the main creased, r/t declined by a factor of 3.48 down the genera- structural component, the C-ring cartilage, becomes stiffer with tions. At the optimal length for active force development, maturation (12) and that the cartilage type changes with age (13). the passive, active, and total stresses decreased signifi- Furthermore, even brief periods of ventilation induce marked cantly as a function of generation. The receptor-mediated changes in the structure of the preterm trachea (9). The func- response to acetylcholine was significantly less in genera- tional force-generating component of the trachea, the tracheal tions O,1, and 2 than in generations 3 and 4. No differences smooth muscle, reduces compliance and therefore collapsibility were found among the various generations in contractility of the immature trachea by developing tone (5, 6, 14). Both as measured by the response to KCl. These data suggest contractility and receptor sensitivity to ACh have been shown to that based on the interrelationship between airway mor- rise with maturity in the lamb (15). phometry and force development the trachea is exposed to An abundance of data exists regarding the structure-function greater wall stress than the lower airways during continu- of the adult (1 6- la), newborn (2, 5, 19), and, more recently, the ous positive airway pressure. Taken together, these data preterm (6, 11, 12, 15) trachea. Although data regarding the may help to explain the structural changes, such as trach- trachea are often used to explain the function of all large con- eomegaly, as well as the physiologic changes in airway ducting airways, the structure of the trachea is markedly different reactivity seen in the premature infant after mechanical from that of the more distal airways. This implies that the ventilation. (Pediatr Res 31: 157-162, 1992) functional properties of the trachea may also vary from those of the lower airways. Although several studies have examined con- Abbreviations tractile responses of adult (20-24) and newborn (3, 25) bronchi, only one has examined the function of preterm airway genera- ACh, acetylcholine tions (25). ANOVA, analysis of variance The purpose of this study was to compare regional morphom- ASM, airway smooth muscle etry, length-stress relationships, and pharmacologic responsive- AS, active stress ness of the trachea and more distal airways in the preterm animal. AS,, maximal active force generation (at Lo) To estimate wall stress at the different generational levels, the EGO, concentration producing one-half the maximal re- morphometric parameter r/t, based on Laplace relationships and sponse modified from the study of Ebina et al.