CELLULAR ADAPTATIONS OF SKELETAL-MUSCLES TO CYCLOSPORINE

The aim of this study was to evaluate the cellular response of the dia phragm, extensor digitorum longus (EDL), and soleus (Sol) muscles to c linically relevant doses of cyclosporine administered to male rats ove r 4 wk. Control rats were provided with vehicle only. Muscle fiber typ es, cross-sectional areas, indexes of capillarity, and succinate dehyd rogenase (SDH) activity were determined by quantitative histochemistry . Myosin heavy chain isoforms were identified by SDS-PAGE, and their p roportions were measured by scanning densitometry. Serum cyclosporine level, 20-24 h after the last dose of cyclosporine, was 145 +/- 81 ng/ ml. Final body weight and muscle mass were similar between the cyclosp orine and control groups. In the diaphragm, EDL, and Sol, no differenc es were observed between the groups with regard to fiber type proporti ons, fiber cross-sectional areas, and proportions of myosin heavy chai n isoforms. In the EDL, reductions, both in SDH activity in type I, II x, and IIb fibers (-26 to -37%) and in indexes of capillarity (-18 to -37%), were noted. In the Sol, SDH activity and capillarity were simil ar between the groups. In the diaphragm of cyclosporine-treated rats, there was significant reduction in the number of capillaries around in dividual fibers (-5%), whereas levels of SDH activity tended to be low er. This suggests that activation history may in part determine muscle -specific responses to cyclosporine. We speculate that reduced oxidati ve activity and capillarity of some limb muscles contribute to reduced exercise capacity and the ''deconditioned state'' observed in patient s receiving cyclosporine after successful solid-organ transplantation.