Effect of passive stretch and calcium in the pathophysiology of central core lesions in chronically shortened muscle fibers

The concept of muscle mass plasticity is well known. An over loaded muscle will hypertrophy (grow in size) and a disused and unloaded muscle will atrophy (decrease in size). Other important aspects of adult muscle plasticity are often overlooked, such as the role of length on muscle health. Hindlimb suspension unloading (HSU) is a ground-based model designed to simulate the effects of microgravity unloading on the musculoskeletal system. In this model, gravity causes the hind foot of the rat to drop and abbreviate the contraction range of the soleus. HSU for 12 days has been shown to cause central core-like lesions (CCLs), an extensive focal breakdown of myofibrils caused by the muscle shortening. The hypothesis tested in this thesis was that brief daily stretch of the calf muscles prevents CCL formation. The soleus muscles of HSU Sprague Dawley male rats were lengthened by unilateral ankle splinting at 30°. Compared to the non-splinted side, splinting for 10 or 20 min per day in awake rats had similar effects on soleus fiber lesions, significantly (p<0.01) decreasing CCLs by 88% and 91%, respectively. In addition, splinting awake rats significantly (p<0.01) reduced atrophy compared to control muscle wet weight. Furthermore, the 33% reduction in atrophy after 20 min splinting was significantly (p<0.05) greater than that observed (17%) for 10 min once a day. Bilateral soleus EMG recording in HSU rats revealed significantly (p<0.05) higher levels of contractile activity on the splinted side during splinting. To isolate the effects of stretch from isometric contractile activity, muscle contractions were eliminated by whole animal anesthesia with isoflurane vapor during the 10 min daily splinting. The percentage of fibers with CCLs was significantly (p<0.05) reduced by 57%, and the average lesion size was 29% smaller in the stretched muscle compared to the non-treated side. Soleus muscle wet weight and fiber area were unaltered by splinting, i.e., splinting in an anesthetized rat did not prevent atrophy. These finding indicate that loaded contractions during splinting are necessary to prevent muscle fiber atrophy. The effects of passive stretch were studied further in a rat tenotomy model where the Achilles tendon is sectioned and the soleus muscle shortens extensively, producing CCLs by day 7 in greater numbers and severity than HSU. A study was performed with the soleus analyzed for CCL% at 1, 2, 3, 4 and 7 days post tenotomy to characterize quantitatively the temporal changes in lesion formation. (Abstract shortened by UMI.).