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Decreased number of acetylcholine receptors is the mechanism that alters the time course of muscle relaxants in myasthenia gravis: a study in a rat model

Published online by Cambridge University Press:  28 July 2005

A. De Haes ,
J. H. Proost ,
M. H. De Baets ,
M. H. W. Stassen ,
M. C. Houwertjes  and
J. M. K. H. Wierda
A. De Haes
Affiliation:
University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands
J. H. Proost
Affiliation:
University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands
M. H. De Baets
Affiliation:
University of Maastricht, Research Institute of Brain and Behavior, Department of Neurology, Maastricht, The Netherlands
M. H. W. Stassen
Affiliation:
University of Utrecht, Department of Cell Biology, Utrecht, The Netherlands
M. C. Houwertjes
Affiliation:
University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands
J. M. K. H. Wierda
Affiliation:
University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands
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Extract

Summary

Background: In myasthenic patients, the time course of action of non-depolarizing neuromuscular blocking agents is prolonged and the sensitivity is increased. We used our antegrade perfused rat peroneal nerve anterior tibialis muscle model to investigate if this altered time course of effect and sensitivity can be explained by the decreased acetylcholine receptor concentration that is caused by the disease. Methods: Functional acetylcholine receptors were reduced by administration of α-bungarotoxin or by injecting monoclonal antibodies against rat acetylcholine receptors (experimental autoimmune myasthenia gravis). After induction of anaesthesia, the model was set up and perfusion of the tibialis anterior muscle with blood was started. After stabilization of the twitch, rocuronium or pancuronium were infused until 90% block was obtained. Twitch data and infusion data were recorded and used to calculate the time course of effect and potency. Results: The potency of neuromuscular blocking agents was increased and the offset of the neuromuscular block was prolonged in both the α-bungarotoxin groups and the experimental autoimmune myasthenia gravis groups compared to controls. Conclusion: This study shows that the increased sensitivity to neuromuscular-blocking agents in myasthenia gravis can be accounted for by a decreased number of acetylcholine receptors. It also shows that the antegrade perfused rat peroneal nerve anterior tibialis muscle model is a suitable model to study the effects of myasthenia gravis on the time course of effect of neuromuscular blocking agents.

Keywords

NEUROMUSCULAR NON-DEPOLARIZING AGENTS, pancuronium, rocuronium, α-bungarotoxinMODELS ANIMAL, ratMYASTHENIA GRAVIS AUTOIMMUNE EXPERIMENTALNEUROMUSCULAR BLOCKADE, onset, recovery
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 22 , Issue 8 , August 2005 , pp. 591 - 596
Copyright
© 2005 European Society of Anaesthesiology

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