Respiratory muscle fiber remodeling in chronic hyperinflation: dysfunction or adaptation?

Abstract

Clanton TL, Levine S. Respiratory muscle fiber remodeling in chronic hyperinflation: dysfunction or adaptation? J Appl Physiol 107: 324 -335, 2009. First published April 9, 2009 doi:10.1152/japplphysiol.00173.2009.-The diaphragm and other respiratory muscles undergo extensive remodeling in both animal models of emphysema and in human chronic obstructive pulmonary disease, but the nature of the remodeling is different in many respects. One common feature is a shift toward improved endurance characteristics and increased oxidative capacity. Furthermore, both animals and humans respond to chronic hyperinflation by diaphragm shortening. Although in rodent models this clearly arises by deletion of sarcomeres in series, the mechanism has not been proven conclusively in human chronic obstructive pulmonary disease. Unique characteristics of the adaptation in human diaphragms include shifts to more predominant slow, type I fibers, expressing slower myosin heavy chain isoforms, and type I and type II fiber atrophy. Although some laboratories report reductions in specific force, this may be accounted for by decreases in myosin heavy chain content as the muscles become more oxidative and more efficient. More recent findings have reported reductions in Ca 2ϩ sensitivity and reduced myofibrillar elastic recoil. In contrast, in rodent models of disease, there is no consistent evidence for loss of specific force, no consistent shift in fiber populations, and atrophy is predominantly seen only in fast, type IIX fibers. This review challenges the hypothesis that the adaptations in human diaphragm represent a form of dysfunction, secondary to systemic disease, and suggest that most findings can as well be attributed to adaptive processes of a complex muscle responding to unique alterations in its working environment. diaphragm; fiber type; sarcomere; skeletal muscle; emphysema THIS REVIEW IS INTENDED TO bring readers up to date with accumulating evidence that the diaphragm undergoes remarkable adaptations to chronic hyperinflation and chronic lung obstruction. Some of these adaptations are expected, based on well known responses of limb muscle to chronic changes in length and mechanical load, but others appear to be surprisingly unique, revealing aspects of muscle plasticity and pathology that are not anticipated from known basic science concepts. We will concentrate this review on what has been observed, primarily at the muscle fiber level in both animals and humans, with primary emphasis on the diaphragm. There have been several excellent previous reviews of this area, and the reader is encouraged to refer to these (13,41,58,65,66). Where possible, we will attempt to complement, update, and at times challenge current concepts with the purpose of furthering dialogue and promoting further inquiry. LENGTH PLASTICITYThe diaphragm, like all other muscles, exhibits a characteristic length-tension relationship analogous to the Frank-Starling curve for the heart. As length is increased in the relaxed muscle, a passive length-tension cu...

Medium term effects of including manual therapy in a pulmonary rehabilitation program for chronic obstructive pulmonary disease (COPD): a randomized controlled pilot trial.

“…21 In an attempt to optimize their force-generating capacity and increase fatigue resistance, the respiratory muscles adapt by dropping sarcomeres and contracting. 58 This finding is supported by the presence of upregulation of IL-6 gene expression in respiratory muscles such as the intercostal muscles. 61 As IL-6 expression is induced by muscle contraction, 62 upregulation is seen as evidence that an adaptive response to the increase in contractile demand has occurred.…”

“…41 This explanation relies on respiratory muscle remodeling and its role in maintaining CWR. 58 Respiratory muscle remodeling is the product of respiratory muscle fatigue and dynamic hyperinflation and results in an uncoupling in the relationship between respiratory effort and tidal volume. 16 This phenomenon, referred to as neuromechanical uncoupling, 20 occurs when respiratory efforts are not rewarded appropriately in terms of tidal volume generated during each breath 21 and is considered a strong determinant of dyspnea in COPD.…”

“…This change perpetuates the increase in CWR. 58,64 When applied to the thoracic cage MT may release some of the rib cage's natural elastic recoil, temporarily easing one of the elements perpetuating CWR. With a 'temporary' improvement in chest wall recoil, the effort of breathing becomes less.…”

A Review of the Ultrasound Assessment of Diaphragmatic Function in Clinical Practice

“…In 1983, Macklem et al [86] reported the negative effects of lung hyperinflation on the reduction of the appositional area and on the relationship between the costal and crural components of the muscle. Yet, in this chronic disease, adaptation phenomena may compensate for the reduced length-tension relationship due to increased lung volumes or increased resistive load [87]. This might explain the variable findings ranging from normal to reduced function reported in studies conducted with the US technique [82,84,86,87].…”

“…Yet, in this chronic disease, adaptation phenomena may compensate for the reduced length-tension relationship due to increased lung volumes or increased resistive load [87]. This might explain the variable findings ranging from normal to reduced function reported in studies conducted with the US technique [82,84,86,87]. For instance, Baria et al [85] reported no significant difference in diaphragm thickness between control subjects and patients with COPD, with the exception of the subgroup with severe air trapping.…”