Abnormal mitochondria and sarcoplasmic changes in rabbit skeletal muscle induced by immobilization.
Immobilization of the rabbit knee in extended position results in damage to the vastus intermedius profundus (VIP) muscle. To examine the mechanisms involved in initiation of the injury, we studied the light and electron microscopic morphology of the VIP muscle, as well as the activity and distribution of NADH tetrazolium reductase (NADH-TR) in the affected muscle, and determined serum total creatine kinase (CK) activity in immobilized rabbits. The VIP muscle of the immobilized right hindlimb was removed at various time points (10 h, 24 h, 36 h and 48-72 h, n=5 for each time point). The nonimmobilized left hindlimb and five nonimmobilized animals served as controls. No morphological changes were observed by light microscopy within 48-72 h in routine stainings. Transient ultrastructural abnormalities, including abnormal cristae, matrix lucencies and mild swelling of mitochondria, were observed between 10 h and 36 h of immobilization, subsiding by 48-72 h. On the other hand, progressive disorganization of myofibrils with breaking-up of Z-bands and an increase in the number and size of sarcoplasmic lipid vacuoles was seen with increasing duration of immobilization. NADH-TR activity at subsarcolemmal locations had decreased by 10 h and disappeared by 24 h of immobilization, while the intermyofibrillar mitochondria remained unaltered. Serum total CK activity began to increase by 2 h of immobilization and reached a peak by 24 h. The results indicate that already a few hours of immobilization of the rabbit knee in extension leads to signs of metabolic disturbance of the VIP muscle and sarcolemmal leakage. The simultaneous occurrence of transient mitochondrial abnormalities, transient CK efflux and progressive myofibrillar damage suggests the operation of multiple adverse mechanisms already at the onset of disuse muscle atrophy.
The Haartman Institute, Department of Pathology, University of Helsinki, Finland.
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Leivo
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Kauhanen
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JE
Michelsson
D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D007103:Immobilization; D008297:Male; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure*; D018482:Muscle, Skeletal / Q000473:pathology / Q000648:ultrastructure*; D009246:NADH Tetrazolium Reductase / Q000378:metabolism; D011817:Rabbits
D009246:NADH Tetrazolium Reductase; D003402:Creatine Kinase