Comparison of the ultrastructural myopathy induced by anticholinesterase agents at the end plates of rat soleus and extensor muscles.

Rats were treated with single subcutaneous injections of the irreversible AChE inhibitors, sarin (90 to 100 micrograms/kg) or soman (55 micrograms/kg), and with chronic doses of the reversible carbamate inhibitor, pyridostigmine. In surviving animals with severe behavioral symptoms, we examined the end-plate regions of the slow-twitch soleus and the fast-twitch extensor digitorum longus muscles, using the electron microscope. Within 30 min, sarin administration caused a recognizable subjunctional myopathy. The progress of morphologic damage was followed for 7 days, during which time the occurrence of damage diminished. The initial swelling of subjunctional organelles and vacuole generation progressed to the point where nerve terminals and attached postjunctional folds were lifted away from the muscle surface. This appeared to be caused by a combination of enlarging vacuoles and insertion of Schwann and macrophage cells into the lesions, and was followed by degeneration of the postjunctional folds. A new component of anti-AChE myopathy was recognized: progressive swelling of chromatin in subjunctional muscle nuclei. The soleus muscle was considerably more sensitive to these effects than the extensor muscle. Soman had a much less prominent ultrastructural effect on the muscle end plates. Chronic pyridostigmine treatment had effects similar to those of a single sarin injection on the soleus as well as a pronounced effect on the extensor muscle.