Stretch-induced changes in constricted lung parenchymal strips: role of extracellular matrix

Abstract

Stretch-induced changes in constricted lung parenchymal strips: role of extracellular matrix. F.G. Salerno, A. Fust, M.S. Ludwig. #ERS Journals Ltd 2004. ABSTRACT: Large amplitude oscillations of contracted airway smooth muscle cause relative relaxation of the preparation. However, little is known about the effect of mechanical stretch on distal lung behaviour.Rat parenchymal strips were suspended in an organ bath and attached at one end to a force transducer and at the other end to a servo-controlled lever arm that effected length changes. Mechanical impedance of the strip was measured by applying a complex signal consisting of pseudorandom length oscillations of varying frequencies . A constant phase model was fit to changes in length and tension to calculate tissue damping (G) and elastance (H). Hysteresivity was calculated as G/H. Impedance was measured before and after sinusoidal length oscillation at different amplitudes (1, 3, 10 and 25% of resting length) at a frequency of 1 Hz under baseline conditions and after acetylcholine-induced constriction.Oscillations of 10 and 25% amplitudes significantly decreased the G and H of the lung strip. The effect of length oscillations was no different in control versus constricted strips.These data suggest that in the distal lung, large stretches affect the structural components of the extracellular matrix rather than the contractile elements. Eur Respir J 2004; 23: 193-198 Understanding the mechanisms underlying the effect of a deep inspiration on lung mechanics has implications for the understanding of asthma pathophysiology. Deep inspirations taken before or after a methacholine challenge decrease the bronchoconstrictor response in normal subjects but not in asthmatics [1,2]. Normal subjects, when asked to refrain from taking deep inspirations after a methacholine (MCh) challenge, behave similarly to hyperresponsive subjects [3]. These observations suggest that the protective effect of deep inspirations on airway narrowing is reduced or absent in asthmatics, a characteristic that may differentiate them from normal subjects. Studies in isolated airway smooth muscle (ASM), which attempt to reproduce the in vivo airway response to tidal breathing and deep inspirations, show that ASM constricts less under dynamic conditions [4]. These data suggest that the effect of lung volume fluctuations on airway narrowing comes from alterations in the ASM.An alternative hypothesis is that the differential effect of deep inspiration in asthmatics compared with controls relates to different lung tissue mechanical properties, because of differences in the extracellular matrix or because of effects on airway-parenchymal interdependence. The lung tissue is a viscoelastic material, and, by definition, viscoelastic materials display hysteresis. FROEB and MEAD [5] theorised that airways also display hysteresis, and the relative hysteresis of these two structures would determine the effect of a deep breath on airway calibre because of the mechanical interdependence between airways and the...

Thoracic percussion yields reversible mechanical changes in healthy subjects

“…Thus, a reduction in regional lung compliance and a redirectioning of blood Xow and ventilation away from these regions would ensue (Oldmixon et al 2001). Deep breaths cannot reverse pneumoconstriction, but lung parenchyma stretching reduces the elastance possibly by changing the ultrastructural arrangement of the connective tissue matrix (Salerno et al 2004). In this context, the normalization of dynamic compliance after DB reported herein could be explained.…”

The extracellular matrix of the lung and airway responsiveness in asthma

“…When isolated lung tissue is exposed in vitro to elastase, an enzyme that digests elastin and collagen disrupting the three-dimensional network of fibres that compose the architecture of the tissue, lung compliance increases [4]. The extracellular matrix is also responsible for a large part of the lung tissue hysteretic properties, and of the energy dissipation occurring during breathing accounted for by lung tissue resistance [5].…”

“…Indeed, it has been demonstrated that it is a shortening velocity rather than force generation per unit of muscle mass that is related to bronchial hyperresponsivenss [10]. Another mechanism, possibly relating extracellular matrix and asthma, is the ability of lung volume excursions to relax airway smooth muscle and decrease lung elastance [5].…”

Reconstruction is not renovation – the role of remodeling in asthma

“…In response to different ECM components, such as fibronectin, collagen and perlecan, the proliferation, survival and inflammatory mediator release from smooth muscle cells can be altered 80–83. Lung cells also possess the ability to modulate the surrounding ECM in response to factors such as physical stress and soluble mediators 77,84,85. Moreover, we have previously shown that the ECM produced by asthmatic cells can induce cells from non-asthmatic subjects to assume the characteristics of those from asthmatic subjects 77…”