Nerve Agent Toxicity and Its Prevention at the Neuromuscular Junction; an Analysis of Acute and Delayed Toxic Effects in Extraocular and Skeletal Muscle

摘要

The nerve agent soman (0.080 mg/kg s.c.), as well as other organophosphates in concentrations that cause cholinergic symptoms, DFP (1.5 mg/kg s.c.), paraoxon (0.23 mg/kg s.c.), and tertiary (0.2 mg s.c.) and quaternary phospholine (0.090 mg/kg s.c.9 induced a progressive, dose-related necrosis in rat skeletal muscle fiber. The severity of the myopathy depended on a critical decrease and duration of AChE inhibition. The fast type Ii fibers appeared to be the more affected fibers in all muscles tested. The necrotic nerve fibers were repaired within one week. Examination of muscle fibers 2 and 3 weeks after a single injection of soman showed a large number of ragged red fibers in the diaphragm and soleus muscle. Following AChE inhibition, the 4S molecular form of AChE showed the fastest recovery as compared with the 10S, 12S and 16S forms. The halftime recovery rate of AChE after inhibition depended on the inhibitor used and the tissue investigated. In general, halftime rate of recovery was slowest in brain and nerve and fastest in SOL and EDL muscle. AChE activity of peripheral nerve was barely inhibited by soman and had recovered to control activity within 24 hours.