Fine structure of muscle in human disuse atrophy: significance of proximal muscle involvement in muscle disorders.

The universal occurrence of weakness of skeletal musculature on disuse, however produced, and the paucity of published reports on the fine structural changes in human disuse atrophy, prompted the present investigation. The quadriceps muscle of a leg immobilized in plaster cast (for fracture) and of the opposite non-immobilized limb was biopsied in four adult males, after periods of immobilization from 50 to 75 days. These 8 muscle specimens were examined for histopathological changes, and muscle fibre diameters were measured by micrometry from paraffin sections. The histograms revealed a larger proportion of small fibres (less than 20 micron) and a smaller proportion of large fibres (greater than 40 micron) in the immobilized limb compared to the opposite. Thus, light microscopy showed only atrophic changes. This was confirmed by electronmicroscopy, where atrophy of few to several muscle fibres was seen in the form of loss of myofibrils, collapse and folding of the basement membrane and prominence of glycogen or muscle nuclei. The atrophic change was more severe in the immobilized limbs, but it was also noticeable in all the non-immobilized limbs. Degenerative changes, especially disorganization and breakdown of myofibrils, and fragmentation of plasma membrane, were also seen in occasional atrophied muscle fibres, again more frequently in the immobilized limb. Lipofuscin was often found accumulated in muscle fibres and occasionally in endothelial cells of intramuscular blood vessels; the latter showed prominent pinocytotic vesicles or thickened basement membrane. It is concluded that both atrophy and degeneration of fibres of proximal muscles can occur as non-specific consequences of disuse of the limb in man, that degeneration is a latter and more severe change, that muscles even of the non-immobilized leg are subjected to disuse atrophy during bed-rest, and that the proximal muscles in man seem to have a natural susceptibility to atrophy and degeneration in any muscular disorders.