Interval between simulated deep inspirations on the dynamics of airway smooth muscle contraction in guinea pig...

A certain amount of time is required to achieve a maximal contraction from airway smooth muscle (ASM) and stretches of substantial magnitude, such as the ones imparted by deep inspirations (DIs), interfere with contraction. The duration of ASM contraction without interference may thus affect its shortening, its mechanical response to DIs and the overall toll it exerts on the respiratory system. In this study, the effect of changing the interval between DIs on the dynamics of ASM was examined in vitro. Isolated bronchi derived from guinea pigs were held isotonically and stimulated to both contract and relax, in a randomized order, in response to 10-5 M of methacholine and 10-6 M of isoproterenol, respectively. Interference to ASM was inflicted after 2, 5, 10 and 30 min in a randomized order, by imposing a stretch that simulated a DI. The shortening before the stretch, the stiffness before and during the stretch, the post-stretch elongation of ASM and the ensuing re-shortening were measured. These experiments were also performed in the presence of simulated tidal breathing achieved through force fluctuations. The results demonstrate that, with or without force fluctuations, increasing the interval between simulated DIs increased shortening and post-stretch elongation, but not stiffness and re-shortening. These time-dependent effects were not observed when ASM was held in the relaxed state. These findings may help understand to which extent ASM shortening and the regulatory effect of DI are affected by changing the interval between DIs. The potential consequences of these findings on airway narrowing are also discussed.