Accumulating Evidence for Increased Velocity of Airway Smooth Muscle Shortening in Asthmatic Airway Hyperresponsiveness

Gijs Ijpma,Anne-Marie Lauzon,Oleg Matusovsky

doi:10.1155/2012/156909

Abstract

It remains unclear whether airway smooth muscle (ASM) mechanics is altered in asthma. While efforts have originally focussed on contractile force, some evidence points to an increased velocity of shortening. A greater rate of airway renarrowing after a deep inspiration has been reported in asthmatics compared to controls, which could result from a shortening velocity increase. In addition, we have recently shown in rats that increased shortening velocity correlates with increased muscle shortening, without increasing muscle force. Nonetheless, establishing whether or not asthmatic ASM shortens faster than that of normal subjects remains problematic. Endobronchial biopsies provide excellent tissue samples because the patients are well characterized, but the size of the samples allows only cell level experiments. Whole human lungs from transplant programs suffer primarily from poor patient characterization, leading to high variability. ASM from several animal models of asthma has shown increased shortening velocity, but it is unclear whether this is representative of human asthma. Several candidates have been suggested as responsible for increased shortening velocity in asthma, such as alterations in contractile protein expression or changes in the contractile apparatus structure. There is no doubt that more remains to be learned about the role of shortening velocity in asthma.

Highlights

It has long been known that deep inspirations (DI) in healthy subjects have both bronchoprotective and bronchodilating effects
Solway and Fredberg have suggested that smooth muscle with a higher shortening velocity may not benefit as much from the airway smooth muscle (ASM) stretches caused by tidal breathing and deep inspirations, as the increased shortening velocity may lead to a faster return to a prestretch length [3]
This study does not directly prove that shortening velocity is increased in asthma; it does suggest a mechanism by which shortening velocity could be increased without changing the force generating capacity of ASM

Summary

Introduction

It has long been known that deep inspirations (DI) in healthy subjects have both bronchoprotective and bronchodilating effects. In asthmatics this rate was significantly higher While both asthmatics and controls had reduced airway resistance directly after DI, a few minutes later airway resistance in asthma was often increased relative to pre-DI levels, while healthy subjects’ airway resistance remained lower. This difference in the rate at which airway resistance is regained is hard to explain with traditional ideas of how airway smooth muscle (ASM) contributes to airway hyperresponsiveness (AHR), that is, increased ASM mass and/or increased ASM force. In this paper we will discuss the varying approaches that have been taken by us and other researchers to assess if and how shortening velocity in asthma is increased and the associated challenges and reservations with each approach

Is Shortening Velocity Increased?

How Is Shortening Velocity Changed?

Conclusion