Muscle Fibre Splitting and Regeneration in Diseased Human Muscle

In soleus muscle of rat, necrosis of muscle fibres within a grossly intact endomysium was produced by 60–70°C Ringer's solution injected into the space around the muscle. After 2 weeks regenerated fibres appeared to be fragments of ‘split’ fibres. In split fibres of patients with myopathy all stages of myogenesis were seen in electron micrographs. Hence splitting of muscle fibres is thought to indicate regeneration rather than degeneration. Based on the morphology of the clefts through split fibres and of normal fetal myogenesis a hypothetical mechanism for splitting of muscle fibres is proposed. Myoblasts, myotubes and myofibres occur within a common basement membrane separated only by plasma membranes and a 20 nm wide gap. In light microscopy they appear as a single fibre. Many meshes of the endomysial framework remain empty and condense around regenerating fibres. Myotubes and young myofibres fuse laterally or become detached and appear by light microscopy to be fragments of a longitudinally split fibre. Though encircled by thick endomysial sheaths, connective tissue between them is sparse. The site of fusion may be marked by a strand of mitochondria or by internal nuclei. Incomplete fusion results in branched fibres or short longitudinal clefts or cavities. The prerequisite of this hypothesis is that regeneration is focal and takes place in a grossly intact endomysium. Repeated death of muscle fibres and focal regeneration in human myopathic muscle lead to dissociation of parenchyma and connective tissue. The mechanism is similar to the formation of pseudolobuli in cirrhosis of the liver.