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Use of Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats
Citation:
FINLEY, D., X. WANG, J. GRAFF, AND D. W. HERR. Use of Single Fiber Electromyographic Jitter to Detect Acute Changes in Neuromuscular Function in Young and Adult Rats. TOXICOLOGY. Elsevier Science Ltd, New York, NY, 59(2):108-119, (2009).
Impact/Purpose:
This manuscript describes a method to quantify neuromuscular jitter in adult and juvenile animals using single fiber electromyography (SFEMG). The effects of different needle placement and criterion amplitude used in calculating the mean consecutive difference (MCD) did not alter the results. Disruption of neuromuscular transmission with decamethonium did change MCD values in adult or juvenile rats. This result was found in the presence of an increased occurrence of blocking of muscle action potentials (MAP), and a greater decrease in MAP amplitude between the first and fourth responses. Treatment with the reversible cholinesterase (ChE) inhibitor physostigmine resulted in minimal changes in the MCD values in adult or juvenile animals, in the presence of at least 35% inhibition of muscle ChE activity. However, age- and stimulation frequency-related changes were observed. Control MCD values in adult and juvenile rats were determined. This technique described is adaptable to multiple ages and had direct clinical correlates with human measures, and will be a useful method to examine changes in neuromuscular function.
Description:
INTRODUCTION: Exposure to irreversible cholinesterase (ChE)-inhibiting compounds, such as organophosphates may produce neuromuscular dysfunction. However, less is known about changes in neuromuscular transmission after treatment with reversible ChE-inhibitors. These studies adapted single fiber electromyography (SFEMG) techniques to quantify neuromuscular jitter in adult and juvenile rats after treatment with agents that alter cholinergic neurotransmission. METHODS: Anesthetized adult and juvenile rats were tested using stimulation SFEMG, recorded in the gastrocnemius muscle, after stimulation in the sciatic notch region. The influence of electrode placement, treatment with decamethonium (to disrupt neuromuscular transmission) or physostigmine (reversible ChE inhibitor), and the impact of varied stimulation frequency were quantified. RESULTS: No significant effects of needle placement or criterion amplitude were observed when calculating the mean consecutive difference (MCD). Treatment with decamethonium did not alter MCD values in adult or juvenile rats. However, decamethonium produced an increased blocking of muscle action potentials (MAP) in juveniles. Also, when stimulated at 9.09 Hz, both adult and juvenile animals had a greater decrease in MAP amplitude between the first and fourth responses (T(1)-T(4) decrement) after treatment with decamethonium. Prior to treatment with decamethonium, the T(1)-T(4) decrement averaged about 3 fold greater in juveniles than adults, and was larger at 3.03 and 9.09 Hz than with 0.91 Hz stimulation. Treatment with physostigmine resulted in at least 50% inhibition of muscle ChE activity, but produced minimal changes in the MCD values in adults or juveniles. Combined over treatments and stimulation frequencies, the median MCD for juveniles (11.6 micros) was less than that for of adults (18.8 micros). In juveniles, the median MCD increased from 9.3 micros to 13.9 micros as the stimulation rate was increased from 0.91 to 9.09 Hz. This stimulus-dependent change was more evident in juveniles than in adults. DISCUSSION: A technique was developed to record stimulation SFEMG and neuromuscular jitter, in vivo, in adult and juvenile rats. The method was sufficiently sensitive to detect age-related differences, potentially allowing developmental processes to be examined. Based on the literature and the current data, the technique appears to be more sensitive to prolonged inhibition of ChE enzymes than the reversible inhibition produced by physostigmine.
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JOURNAL OF PHARMACOLOGICAL TOXICOLOGY
Single fiber electromyographic jitter and detection of acute cha