Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease

Abstract

Pulmonary hyperinflation impairs the function of the diaphragm in patients with chronic obstructive pulmonary disease (COPD). However, it has been recently demonstrated that the muscle can counterbalance this deleterious effect, remodelling its structure (i.e. changing the proportion of different types of fibres). The aim of this study was to investigate whether the functional impairment present in COPD patients can be associated with structural subcellular changes of the diaphragm.Twenty individuals (609 yrs, 11 COPD patients and 9 subjects with normal spirometry) undergoing thoracotomy were included. Nutritional status and respiratory function were evaluated prior to surgery. Then, small samples of the costal diaphragm were obtained and processed for electron microscopy analysis.COPD patients showed a mean forced expiratory volume in one second (FEV1) of 609% predicted, a higher concentration of mitochondria (n mit ) in their diaphragm than controls (0.620.16 versus 0.460.16 mitochondrial transections (mt) . mm -2 , p<0.05). On the other hand, subjects with air trapping (residual volume (RV)/total lung capacity (TLC) >37%) disclosed not only a higher n mit (0.630.17 versus 0.430.07 mt . mm -2 , p<0.05) but shorter sarcomeres (L sar ) than subjects without this functional abnormality (2.080.16 to 2.270.15 mm, p<0.05). Glycogen stores were similar in COPD and controls. The severity of airways obstruction (i.e. FEV1) was associated with n mit (r=-0.555, p=0.01), while the amount of air trapping (i.e. RV/TLC) was found to correlate with both n mit (r=0.631, p=0.005) and L sar (r=-0.526, p<0.05). Finally, maximal inspiratory pressure (PI,max) inversely correlated with n mit (r-0.547, p=0.01).In conclusion, impairment in lung function occurring in patients with chronic obstructive pulmonary disease is associated with subcellular changes in their diaphragm, namely a shortening in the length of sarcomeres and an increase in the concentration of mitochondria. These changes form a part of muscle remodelling, probably contributing to a better functional muscle behaviour. Eur Respir J 1999; 13: 371±378. Chronic obstructive pulmonary disease (COPD) is a respiratory condition mainly characterized by persistent airflow limitation [1]. It affects >5% of the general population [2], is a cause of permanent disability and constitutes one of the leading and increasing causes of death in developed countries [3].The function of the diaphragm, the main respiratory muscle, can be impaired in patients with COPD owing to both airways obstruction and pulmonary hyperinflation (air trapping) [4±6]. However, it has been demonstrated that this deleterious effect can be partially counterbalanced by the muscle [7]. TAMAOKI [8] found that fibres were hypertrophic in the diaphragm of guinea-pigs with elastaseinduced emphysema. Recently, LEVINE et al.[9] have demonstrated that patients with severe COPD show a higher percentage of type I fibres in their diaphragm than subjects with normal lung function or mild COPD. These and other chan...

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

“…Parallel to the increases in oxidative enzyme capacity, diaphragm mitochondrial density, measured with electron microscopy, has been shown to increase in patients with COPD by an average of ϳ50% (59), and the mitochondrial oxidative capacity of permeabilized fibers increases as well (77). Both of these variables were also shown to increase as a function of disease severity (59,77).…”

“…Others have challenged the extent to which the diaphragm length adapts, by evaluating absolute sarcomere length in frozen biopsy specimens from COPD patients (59). They observed that average sarcomere length was shorter in emphysema than in comparable controls and that the greater degree of hyperinflation or disease severity corresponded with shorter sarcomere lengths.…”

Oxidised proteins and superoxide anion production in the diaphragm of severe COPD patients

“…Several reports have shown that in severe COPD the main inspiratory muscle, the diaphragm, undergoes adaptive modifications that probably render the overloaded muscle more resistant to fatigue [4][5][6][7][8]. However, there is growing evidence that in vitro fibre contractile function is also impaired in the diaphragms of patients with COPD [9], even at early stages of their disease, as shown by reduced myosin heavy chain (MyHC) content and increased protein degradation via the ubiquitin-proteasome pathway [10,11].…”

“…During thoracotomy, because of localised lung lesions, diaphragm biopsy specimens were obtained from the anterior costal diaphragm lateral to the insertion of the phrenic nerve [5,14].…”

Avaliação clínica da capacidade do exercício em pacientes com doença pulmonar obstrutiva crônica

“…In the cases of COPD, the strength of the inspiratory muscles is usually diminished due to mechanical changes caused by low levels of direct insufflation derived from air trapping, and not because of changes in muscle contractile properties 54,55 . Conventional strength measurements are generated from maximum isometric contractions of the residual volume (RV) for the inspiratory muscles, and from the total pulmonary capacity (TPC) for the expiratory muscles.…”