MRS OF PATS W/ AIDS DEMENTIA COMPLEX: MULTICENTER ACTG 301 DRUG EVAL PROGRAM

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Inactivity or disuse as a result of immobilization, bed rest, non-weight bearing, or denervation causes many adaptive changes in skeletal muscle with muscular dysfunction as a final outcome. Loss of muscle mass or muscular atrophy is one of the most recognized consequences of disuse. Inactivity has also been shown to cause metabolic alterations in skeletal muscle, the most important being elevated basal inorganic phosphate (Pi). We have tracked 10 subjects through an 8 week period of cast immobilization of the lower leg followed by ten weeks of rehabilitation. For comparison of changes seen during rehabilitation, we have performed similar testing on 7 control subjects over a ten week period. Immobilization of the ten subjects resulted in skeletal muscle atrophy, an increase in basal inorganic phosphate and decreased force production. 31P NMR was used to show a 43% increase in basal inorganic phosphate in the atrophy group as compared with the control population. The maximum cross-sectional area of the triceps surae was seen to decrease as well. The extent of force loss was greater than the decrease in muscle cross-sectional area, meaning that the atrophic, disused muscle had become less efficient at producing force as compared to control subjects with similar muscle CSAs. Regression analysis of both atrophy and control measurements of MaxCSA versus Force proved statistically significant with the atrophy group generating lower forces at similar MaxCSAs (R2=0.55 in the atrophy group, and 0.70 in the control). Throughout recovery the muscular efficiency in the atrophy group was seen to increase approaching control values at the end of the rehab period. This was accomplished by an increase in Force, maximum CSA, and a decrease in basal inorganic phosphate. The change in muscular efficiency as a result of immobilization, where the extent of force loss and muscle function exceeded the decrease in muscle size suggests that there are other significant factors caused by immobilization that lead to an overall loss in muscul ar efficiency besides muscle atrophy. We believe elevated inorganic phosphate, along with a decrease in muscle size, to be an important contributor to decreased muscle function following immobilization.