Summary
The distribution of myopathic changes produced by phencyclidine (PCP) and restraint was studied in the diaphragm and 6 lower limb muscles of the rat. Fiber-type composition and muscle location did not correlate with the degree of injury; but muscle activity in restraint did correlate. The predominant lesion produced was extensive myofibrillar disruption, which was the only lesion temporally related to the increased plasma creatine phosphokinase (CPK) activity that begins within minutes of treatment. Early on, disoriented, structurally abnormal mitochondria were localized to foci of disrupted myofibrils, but they were absent in such areas at 24h. Significant Z-band smearing, accompanied by focal mitochondrial absence, was first noted at 24h.
In untreated control muscles, Z-band smearing occurred predominantly in the soleus but was not limited to that muscle. The occurrence of Z-band smearing was related to the proportion of mitochondrial-rich fibers in control specimens. On the contrary, the occurrence of myofibrillar disruption was related to the proportion of mitochondrial-poor fibers in the control specimens. In both experimental and control muscle, Z-band smearing occurred predominantly in those specially differentiated peripheral areas in the muscle fiber which are immediately adjacent to transversely coursing blood vessels. These areas normally lack mitochondria. Thus, the mitochondrial absence in areas of Z-band smearing is not of the same significance as the focal mitochondrial loss that occurs in areas of myofibrillar disruption. These findings may apply to the pathogenesis of myofibrillar lesions in general.
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Supported by grants USPHS MH 18396; MH 16, 127, MH 30,938 and Illinois Dept. Mental Health. Dr. Meltzer is recipient of USPHS RCSA MH 47,808. Dr. Kuncl is recipient of USPHS 5T05GM1939-09 (MSTP)
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Kuncl, R.W., Meltzer, H.Y. Lesions of the myofibril in myopathic and normal tissue from seven striated muscles. Acta Neuropathol 45, 83–95 (1979). https://doi.org/10.1007/BF00691885
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DOI: https://doi.org/10.1007/BF00691885