Subcellular adaptation of the human diaphragm in chronic obstructive pulmonary disease

Pulmonary hyperinflation impairs the function of the diaphragm in patients with chronic obstructive pulmonary disease (COPD). However, it has been rec ently demonstrated that the muscle can counterbalance this deleterious effe ct, remodelling its structure (i.e. changing the proportion of different ty pes of fibres). The aim of this study was to investigate whether the functi onal impairment present in COPD patients can be associated with structural subcellular changes of the diaphragm. Twenty individuals (60+/-9 yrs, 11 COPD patients and 9 subjects with normal spirometry) undergoing thoracotomy were included. Nutritional status and r espiratory function were evaluated prior to surgery. Then, small samples of the costal diaphragm were obtained and processed for electron microscopy a nalysis. COPD patients showed a mean forced expiratory volume in one second (FEV1) o f 60+/-9% predicted, a higher concentration of mitochondria (n(mit)) in the ir diaphragm than controls (0.62+/-0.16 versus 0.46+/-0.16 mitochondrial tr ansections (mt) .mu m(-2), p< 0.05). On the other hand, subjects with air t rapping (residual volume (RV)/total lung capacity (TLC) >37%) disclosed not only a higher n(mit) (0.63+/-0.17 versus 0.43+/-0.07 mt.mu m(-2), p<0.05) but shorter sarcomeres (L-sar) than subjects without this functional abnorm ality (2.08+/-0.16 to 2.27+/-0.15 mu m, p<0.05). Glycogen stores were simil ar in COPD and controls. The severity of airways obstruction (i.e. FEV1) wa s associated with n(mit) (r=-0.555, p=0.01), while the amount of air trappi ng (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 (Pl,ma s) inversely correlated with n(mit) (r=-0.547, p=0.01). In conclusion, impairment in lung function occurring in patients with chron ic obstructive pulmonary disease is associated with subcellular changes in their diaphragm, namely a shortening in the length of sarcomeres and an inc rease in the concentration of mitochondria. These changes form a part of mu scle remodelling, probably contributing to a better functional muscle behav iour.