Maturational Changes in Airway Smooth Muscle Structure-Function Relationships

Abstract

ABSTRACT. Airways become less compliant with age. When examined at either extreme of the developmental spectrum, airway smooth muscle (ASM) undergoes changes that parallel the trachea: both passive and active stress increase from preterm to adult. To determine how ASM changes throughout maturation, trachealis muscles from sheep airways of five age groups (group 1, <I10 d gestation; group 2,110-124 d gestation; group 3,125-140 d gestation; group 4, newborn; and group 5, adult) were separated from their cartilaginous supports and cleaned of their mucosa and serosa. The length at which active stress was optimal was determined and passive and active stress were measured. Concentration-effect curves for acetylcholine (ACh) and KC1 were performed at the length at which active stress was optimal. Morphometric analysis of the muscle was performed by computerized image analysis. At the length at which active stress was optimal, both passive and active stress increased with maturation ( p < 0.001).Concentration-effect curves for both ACh and KC1 also showed a significant increase in active stress as a function of dose and of age ( p < 0.002), and the ED50 for ACh decreased with maturation ( p < 0.005). Although muscle length, thickness, and area increased with age (p < 0.005), the ratio of contractile to connective tissue within the muscle bundle remained constant throughout maturation. These data demonstrate that ASM undergoes a progressive increase in contractility and sensitivity to ACh throughout maturation. The inability of immature ASM to generate as much force as adult ASM may in part explain why preterm infants who require positive-pressure ventilation are at risk to sustain structural central airway injury. (Pediatr Res 31: [151][152][153][154][155][156]1992) Abbreviations KBS, Krebs buffer solution Lo, length of muscle at which active stress is optimal A, cross-sectional area ACh, acetylcholine ANOVA, analysis of variance C,, specific compliance of the trachealis muscle Immature airways are compliant structures (1-3). Studies investigating changes in airway mechanics as a function of maturation have shown that compliance decreases progressively from fetus to adult (1, 2, 4).Airway smooth muscle stimulation can decrease airway compliance independently of age (3, 5-7). Recently, differences in airway smooth muscle contractility and passive tension generation have been described between adults and preterms that parallel compliance changes in the trachea as a whole (8). Both active and passive tension of the trachealis itself are 2.5 times greater in the adult than in the preterm airway. Similar trends have been recognized in other smooth muscle systems (9-1 1). Morphologic and/or biochemical changes responsible for these alterations, however, remain poorly understood.There is a clear change in force generation between the extremes of developmental age. Whether the increase in tracheal muscle tone is responsible for the decrease in tracheal compliance, however, is not known. Nor is it known when during developmen...

New aspects of airway mechanics in pre-term infants

“…This suggests that increased airway wall compliance due to immaturity must have a significant influence on far,1 and hence n in pre-term infants. The latter would be consistent with structural findings [22,34].…”

“…One hypothesis is that the structural immaturity of the airway walls results in highly compliant airways, crucially determining flow limitation in immature airways of prematurely born infants. The high compliance of the airway walls in immature animals has been demonstrated in vitro [22,34], but the situation might be different in vivo and/or in human infants, depending on the strength of airway-parenchyma attachments and the relationship between lung and chest wall compliance [24]. This relationship will be further complicated by the tendency of young infants to dynamically elevate their endexpiratory volume, thereby further regulating airway patency and elastic recoil, and by changes in sleep state, which may affect both lung volume and upper airway tone [16,23].…”

Differences in airway wall compliance as a possible mechanism for wheezing disorders in infants

“…However, maximal expiratory flow volume curves measured by the RTC technique cannot distinguish between the effects of airway calibre and airway wall properties on flow limitation. It might be especially important to distinguish these effects in infants since, as has been demonstrated in lambs by PANITCH et al [12]), airway wall compliance is much higher than in later life. In order to understand the developmental basis for wheezing disorders, it is thus important to devise a technique to enable airway calibre and airway wall properties to be separately measured.…”

Human Trachealis and Main Bronchi Smooth Muscle Are Normoresponsive in Asthma

“…Alternatively, any shortterm hormonal effects may not be present because the hormones would be washed out during equilibration or degraded during transport. Maturational studies in sheep (34) and guinea pigs (9) show changes in both contractile force (increase with age) and shortening velocity (strong decrease with age). However, these studies focused on very young animals and little is known about changes in adulthood.…”