Effects of unloading on skeletal muscle mass and function in man

Abstract

An experimental human model of skeletal muscle unloading of one lower limb and confined bedrest were employed to quantitate the adaptive responses to 10 days, 4 or 6 wk of unloading in healthy humans on quadricep skeletal muscle mass and function.

Muscle cross-sectional area (CSA) was assessed using tomographic imaging (CT, MRI). Fiber CSA, type and capillarization and myosin heavy chain (MyHC) composition were determined in biopsy specimens from m. vastus lateralis. Enzyme activity of citrate synthase (CS) and phosphofructokinase (PFK) was analyzed. Strength (peak torque), force-velocity characteristics along with electromyographic (EMG) activity and work capacity were assessed during maximal voluntary knee extension.

Peak torque decreased uniformly across velocities and mode of action by 13% after 10 d and 16-22% after 4 wk unilateral unloading and by 25-30% after 6 wk bedrest. Four wk unloading reduced (17%) work capacity and increased fatigability of exercise comprising three bouts of 30 knee extensions.

Thigh muscle mass decreased by 7% after 4 wk of unilateral unloading and by 11% after 37 days bedrest. The atrophy was more pronounced in the knee extensor (14%) than in adductor (9%) or knee flexor (p>0.05;7%) muscles, suggesting a hierarchy related to weight-bearing activity. Peak torque/knee extensor CSA decreased (13%) in response to 6 wk bedrest suggesting atrophy not to fully account for the loss in strength.

Muscle fiber CSA decreased by 18% after 37 days bedrest but not (p>0.05; 10%) after 4 wk unloading. Type l/type 11 fiber CSA showed no change. Nor did type I or type 11 fiber percentage change. MyHC composition was unaltered after bedrest. Capillaries per fiber or area were unaltered after 4 wk unloading. CS but not PFK activity decreased. Single-fiber analysis in 3 individuals showed a decrease in force-generating capacity per cross-sectional area (specific tension) after bedrest. No change occurred in maximum shortening velocity of pooled single fibers. Neural drive, as reflected in EMG activity, was unaltered after 10 d unloading but decreased (19%) after 6 wk bedrest. EMG activity at a constant submaximal load, increased after 10 d unloading (25%) and 6 wk bedrest (44%), suggesting decreased electromechanical efficiency. Four days of weight-bearing recovery normalized strength following short term (10 d) unload mg while half of the strength loss was recaptured following 4 wk unloading. Seven wk of free reambulation normalized muscle CSA while work capacity was still decreased (7%) following unilateral unloading and strength (7%)was reduced following bedrest. The time required to normalize muscle strength, thus, seems to increase with duration of unloading. A rapid recovery in strength was a consistent finding during the first days of reambulation.

The loss in strength and work capacity was about 5% weekly during the first month of unloading. About two thirds of the loss in muscle function can be accounted for by muscle atrophy. Although neural drive appeared to be reduced a decrease in skeletal muscle force-generating capacity of muscle, e.g., decreased specific tension of muscle must in part be responsible for the impaired muscle function seen after prolonged unloading.