In a physiological and morphological study of the muscles of the hind limb of cats, we demonstrated that immobilization initiates muscle-cell disintegration which is reflected by a decrease in weight to 30 per cent of normal after twenty-two weeks. During this interval, contraction time and relaxation time increase, but they return to normal one week after release from immobility. In immobilized muscle these times increase much less than they do in denervated muscle. Finally in immobilized muscle the tension during both total twitch and tetanus decreases more than muscle weight.

Most of the classic pathological changes in muscle which are visible by light microscopy and have been described in many experiments and in association with disease can be produced by immobility. Immobilized muscle fibers undergo a more or less well defined sequence of degenerative changes in which many fibers remain simply as sarcotubes which are enclosed by basement membrane and contain only fluid, precipitated protein, and fragments of the sarcolemma. If these changes extend throughout an entire fiber, they indicate irreversible damage. Comparison of the changes induced by immobilization with those produced by other means reveals that despite the complex structure of muscle, its responses to injury are relatively limited.

Immobilized skeletal muscle with an intact blood and nerve supply and intact sarcotubes has great regenerative potential after release from immobilization. Restoration of damaged muscle fibers begins three to five days after release. As the result of endomysial proliferation, tubes are formed which guide the regenerating contractile elements during a well defined sequence of regenerative changes.

Muscle degeneration induced by immobilization in a plaster cast and the regeneration that takes place after immobilization is discontinued, provide ideal models for the histochemical and microenzymatic studies that will be required to elucidate the mechanisms that initiate and control muscle degeneration and regeneration. We agree with the too long-neglected admonition of Eisenhauer and Key who, in 1945, remarked that they were not able to extend their investigations on muscle atrophy, but warned, "It is important that this work be carried to its ultimate conclusion because this will place much of the treatment of injured extremities on a sound experimental basis instead of on the basis of accumulated clinical impressions."¹⁷