Muscle fibre atrophy in critically ill patients is associated with the loss of myosin filaments and the presence of lysosomal enzymes and ubiquitin.
Muscle wasting and weakness are common features of patients with critical illnesses, and may impair their recovery. This study examines whether cytoskeletal and contractile proteins are damaged, and which proteolytic mechanisms might be involved, in the muscle fibre atrophy or necrosis associated with the acute myopathy of critically ill patients. Ninety-eight muscle biopsies were obtained by the conchotome method from 57 critically ill patients and examined morphometrically and by immunohistochemical labelling. Sequential biopsies showed a mean reduction in fibre cross-sectional areas of 3-4% per day. More intense immunolabelling for desmin was seen in the smaller fibres of 52% of the biopsies, while immunolabelling for dystrophin, actin and myosin heavy chains was maintained. Myosin ATPase activity was weak in the smaller fibres in some biopsies, and electron microscopy showed the loss of myosin filaments in atrophic fibres. These changes suggest that loss of the filamentous structure of myosin, without degradation of the immunolabelled epitopes, leads to the collapse of the intermyofibrillar desmin network. Fibres with abnormal desmin labelling showed increased cathepsin B, lysozyme and ubiquitin immunolabelling. Nine cases showed increased immunolabelling for heat shock protein 72. The changes in desmin immunolabelling were more prevalent in patients with higher APACHE II scores on admission, but were not related to other clinical features. The results indicate that fibre atrophy is associated with myosin filament depolymerization and the presence of several proteolytic enzymes. In our study, these changes occurred in patients who were critically ill but who did not receive large doses of steroids or neuromuscular blocking agents.
Helliwell
T R
TR
Department of Pathology, University of Liverpool, UK.
Wilkinson
A
A
Griffiths
R D
RD
McClelland
P
P
Palmer
T E
TE
Bone
J M
JM
D000328:Adult; D000368:Aged; D001706:Biopsy; D002401:Cathepsin B / Q000378:metabolism; D003285:Contractile Proteins / Q000502:physiology; D016638:Critical Illness; D003598:Cytoskeletal Proteins / Q000502:physiology; D003893:Desmin / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000201:enzymology*; D008854:Microscopy, Electron; D008875:Middle Aged; D009113:Muramidase / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy / Q000473:pathology*; D009218:Myosins / Q000502:physiology*; D014452:Ubiquitins / Q000032:analysis*
D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D003893:Desmin; D014452:Ubiquitins; D009113:Muramidase; D002401:Cathepsin B; D009218:Myosins