Airway and Parenchymal Strains during Bronchoconstriction in the Precision Cut Lung Slice.

Jonathan E Hiorns,Cécile M Bidan,Ramaswamy Krishnan,Jim P Butler,Loes E M Kistemaker,Oliver E Jensen,Bindi S Brook,Jeffrey J Fredberg,Reinoud Gosens

doi:10.3389/fphys.2016.00309

Abstract

The precision-cut lung slice (PCLS) is a powerful tool for studying airway reactivity, but biomechanical measurements to date have largely focused on changes in airway caliber. Here we describe an image processing tool that reveals the associated spatio-temporal changes in airway and parenchymal strains. Displacements of sub-regions within the PCLS are tracked in phase-contrast movies acquired after addition of contractile and relaxing drugs. From displacement maps, strains are determined across the entire PCLS or along user-specified directions. In a representative mouse PCLS challenged with 10−4M methacholine, as lumen area decreased, compressive circumferential strains were highest in the 50 μm closest to the airway lumen while expansive radial strains were highest in the region 50–100 μm from the lumen. However, at any given distance from the airway the strain distribution varied substantially in the vicinity of neighboring small airways and blood vessels. Upon challenge with the relaxant agonist chloroquine, although most strains disappeared, residual positive strains remained a long time after addition of chloroquine, predominantly in the radial direction. Taken together, these findings establish strain mapping as a new tool to elucidate local dynamic mechanical events within the constricting airway and its supporting parenchyma.

Highlights

Airway smooth muscle (ASM) cells residing within the airway wall, and the tissue in the surrounding parenchyma, are under constantly changing strains during tidal breathing
A few studies have extracted some detailed strain data from precision-cut lung slice (PCLS) (Adler et al, 1998; Brook et al, 2010; Ma et al, 2013), these have been obtained by tracking specific landmarks in the tissue
By contrast, we present a computational strain-mapping tool that is able to characterize heretofore inaccessible mechanical events that bear directly upon the physiology of airway narrowing

Summary

Introduction

Airway smooth muscle (ASM) cells residing within the airway wall, and the tissue in the surrounding parenchyma, are under constantly changing strains during tidal breathing. It is widely recognized that the effect of imposed strains and resulting stresses, as well as internally generated mechanical force, are of crucial importance in normal physiology and are altered in diseases such as asthma and COPD. While complex and inferred in organs and overly simplified in the cultured cell, their generation, transmission, and transduction in the settings of an intact airway remain difficult to measure. There are currently no straightforward approaches to quantify the strains or stresses acting on cells and tissues in their native airway microenvironment. In the absence of such knowledge, the mechanical interactions involved in airway (patho)physiology will remain poorly understood

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