SOMAN-INDUCED MORPHOLOGICAL-CHANGES - AN OVERVIEW IN THE NONHUMAN PRIMATE

A review of the literature was conducted to provide an overview of org anophosphorus (OP)-induced morphological changes in the non-human prim ate. Most studies have evaluated effects of the OP nerve agent soman ( pinacolyl methylphosphonofluoridate), an irreversible inhibitor of ace tylcholinesterase. Soman-induced acute and chronic morphological chang es have been examined. The effects of nerve agent therapy (i.e. pyrido stigmine, praloxidime chloride and atropine), with and without an anti convulsant (i.e. diazepam, midazolam), on soman-induced lesions have a lso been studied. Acute changes in the central nervous system of rhesu s and cynomolgus monkeys exposed to soman alone or soman and therapy, without an anticonvulsant, were characterized by neuronal degeneration and necrosis and neuropil edema. The lesions were usually present in the frontal cortex, entorhinal cortex, amygdaloid complex, caudate nuc leus, thalamus and hippocampus. Morphologically, these lesions resembl e lesions produced by hypoxic-ischemic injury or by seizures and are s imilar to soman-induced changes in other laboratory animals. Nerve age nt therapy supplemented with an anticonvulsant reduced or prevented so man-induced acute neural lesions. Acute changes in non-neural tissues were limited to the heart (e.g. hemorrhage, myofiber necrosis, myocard itis) and skeletal muscle (e.g. myofiber necrosis). Heart lesions in t he non-human primate are similar to OP-induced heart lesions in man. T he pathogenesis of the acute lesions in both the central nervous syste m and heart is discussed. Consistent soman-induced chronic morphologic al changes have not been produced in the rhesus monkey or baboon.