Protective Effect of Early and Late Administration of Pralidoxime against Organophosphate Muscle Necrosis

The objective of the present investigation was to study the protection afforded by a single administration of pralidoxime against the muscle necrosis induced by the organophosphate compound metamidophos at different times after intoxication. The fiber necrosis of the diaphragm muscle was quantified by a morphometric technique, comparing the area fraction occupied by necrotic muscle fibers in animals that received pralidoxime at different times after intoxication, i.e., 0, 1, 3, 6, and 12h. Pralidoxime administration protected metamidophos-induced muscle necrosis in all groups studied except for the 12-h group. The earlier the administration of pralidoxime the greater the protection against muscle necrosis. This protection was not accompanied by complete reactivation of plasma cholinesterase activity. Results support the current opinion that pralidoxime should be administered as soon as possible after organophosphate intoxication, because in addition to reversing the muscarinic effects, early administration of pralidoxime also prevents muscle necrosis—which could impair muscular function and respiratory condition. The time difference between recovery of plasma cholinesterase activity and muscle necrosis protection indicates that this method is not completely trustworthy for patient follow-up, since some improvement may occur in spite of the low plasma cholinesterase activity.