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ACUTE PHARMACOLOGICAL INHIBITION OF CHOLINESTERASE RESULTS IN MINIMAL NEUROMUSCULAR JITTER CHANGES.
Citation:
Finley, D. B. AND D W. Herr. ACUTE PHARMACOLOGICAL INHIBITION OF CHOLINESTERASE RESULTS IN MINIMAL NEUROMUSCULAR JITTER CHANGES. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2001.
Description:
Concern over the lack of available endpoints to assess peripheral nervous system dysfunction after pesticide exposure has led to the search for new laboratory models. Recently our lab adapted the in vivo clinical practice of stimulation single fiber electromyography (SFEMG) for use in laboratory research with adult and juvenile rats. Using SFEMG, a series of 50 compound muscle action potentials (CMAPs), elicited by electrical stimulation of the sciatic nerve, was recorded from the gastrocnemius muscle. The carbamate physostigmine was injected sc (adult doses: 0, 0.05, 0.1, 0.2, 0.3; juvenile doses: 0, 0.025, 0.05, 0.1, 0.2 mg/kg). The mean consecutive difference (MCD), a measure of neuromuscular jitter, was quantified using 0.91, 3.03, and 9.09 Hz stimulation frequencies. The amount of jitter in each stimulation series was used to assess the effects of acute cholinesterase inhibition on neuromuscular function. In addition, cholinesterase activity was determined in the plasma, erythrocytes, brain, and gastrocnemius muscle tissues. Results indicate minimal changes in neuromuscular jitter after physostigmine treatment in adults or juveniles. Significant inhibition of cholinesterase activity was found in all tissues in an age- and dose-dependent manner. Although this study failed to find significant dose-dependent jitter differences after treatment with the carbamate physostigmine, it is possible neuropathic organophosphates may have different effects. More research is necessary to fully explore how the application of stimulation SFEMG can be used to assess effects of cholinesterase inhibition on neuromuscular transmission.
*Funded by the EPA/UNC Toxicology Research Program, Training Agreement CT902908.+This abstract does not necessarily reflect US EPA policy.