Flexibility of microstructural adaptations in airway smooth muscle

Abstract

The airway smooth muscle undergoes an elastic transition during a sustained contraction, characterized by a gradual decrease in hysteresivity caused by a relatively greater rate of increase in elastance than resistance. We recently demonstrated that these mechanical changes are more likely to persist after a large strain when they are acquired in dynamic versus static conditions; as if the microstructural adaptations liable for the elastic transition are more flexible when they evolve in dynamic conditions. The extent of this flexibility is undefined. Herein, contracted ovine tracheal smooth muscle strips were kept in dynamic conditions simulating tidal breathing (sinusoidal length oscillations at 5% amplitude) and then subjected to simulated deep inspirations (DI). Each DI was straining the muscle by either 10, 20 or 30% and was imposed at either 2, 5, 10 or 30 min after the preceding DI. The goal was to assess whether, and the extent by which, the time-dependent decrease in hysteresivity is preserved following the DI. The results show that the time-dependent decrease in hysteresivity seen pre-DI was preserved after a strain of 10%, but not after a strain of 20% or 30%. This suggests that the microstructural adaptations liable for the elastic transition withstood a strain at least twofold greater than the oscillating strain that pertained during their evolution (10 versus 5%). We propose that a muscle adapting in dynamic conditions forges microstructures exhibiting a substantial degree of flexibility.

The cumulative effect of methacholine on large and small airways when deep inspirations are avoided

“…These DIs directly dilate airways and thereby reverse the induced constriction 13–20 . In addition, they stretch the ASM, which is likely to decrease its contractile capacity 21–29 and the ensuing degree of airway responsiveness. In fact, ample evidence supported these notions.…”

“…induced constriction. [13][14][15][16][17][18][19][20] In addition, they stretch the ASM, which is likely to decrease its contractile capacity [21][22][23][24][25][26][27][28][29] and the ensuing degree of airway responsiveness. In fact, ample evidence supported these notions.…”

“…Irrespective of whether the decrease in airway responsiveness caused by DIs occurs through a direct reversal of bronchoconstriction, [13][14][15][16][17][18][19][20] a reduction in ASM contractility, [21][22][23][24][25][26][27][28][29] or a combination thereof, it is likely to provide the false impression that the effect of methacholine is not (or only slightly) cumulative. Interestingly, the fact that the dilating effect of DIs is less effective in asthmatic versus non-asthmatic individuals 17,[30][31][32] is perhaps consistent with the slightly cumulative effect of serial doses of methacholine in the former but not in the latter.…”

“…Additionally, an impressive number of in vitro studies demonstrates that stretching the ASM by a magnitude simulating airway dilation during a DI impairs its forcegenerating capacity. [21][22][23][24][25][26][27][28][29] Therefore, the periodic DIs during the methacholine challenge may also reduce the degree of airway responsiveness by decreasing the contractile capacity of ASM.…”