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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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References

De Haes A, Proost JH, Kuks JB, van den Tol JC, Wierda JMKH. Pharmacokinetic/pharmacodynamic modeling of rocuronium in myasthenic patients is improved by taking into account the number of unbound acetylcholine receptors. Anesth Analg 2002; 95: 588–596.Google Scholar
De Haes A, Proost JH, De Baets MH, Stassen MHW, Houwertjes MC, Wierda JMKH. Pharmacokinetic–pharmacodynamic modelling in case of a decreased number of acetylcholine receptors. A study in myasthenic pigs. Anesthesiology 2003; 98: 133–142.Google Scholar
De Haes A, Houwertjes MC, Proost JH, Wierda JMKH. An isolated, antegrade, perfused, peroneal nerve anterior tibialis muscle model in the rat: a novel model developed to study the factors governing the time course of action of neuromuscular blocking agents. Anesthesiology 2002; 96: 963–970.Google Scholar
Tzartos S, Hochschwender S, Vasquez P, Lindstrom J. Passive transfer of experimental autoimmune myasthenia gravis by monoclonal antibodies to the main immunogenic region of the acetylcholine receptor. J Neuroimmunol 1987; 15: 185–194.Google Scholar
Hoedemaekers AC, Verschuuren JJ, Spaans F et al. Age-related susceptibility to experimental autoimmune myasthenia gravis: immunological and electrophysiological aspects. Muscle Nerve 1997; 20: 1091–1101.Google Scholar
Hoedemaekers AC, Graus Y, van Breda Vriesman P, de Baets M. Age- and sex-related resistance to chronic experimental autoimmune myasthenia gravis (EAMG) in Brown Norway rats. Clin Exp Immunol 1997; 107: 189–197.Google Scholar
Lindstrom JM, Lennon VA, Seybold ME, Whittingham S. Experimental autoimmune myasthenia gravis and myasthenia gravis: biochemical and immunochemical aspects. Ann NY Acad Sci 1976; 274: 254–274.Google Scholar
Verschuuren JJ, Graus YM, Theunissen RO et al. Role of acetylcholine receptor antibody complexes in muscle in experimental autoimmune myasthenia gravis. J Neuro-immunol 1992; 36: 117–125.Google Scholar
Jahn K, Franke C, Bufler J. Mechanism of block of nicotinic acetylcholine receptor channels by purified IgG from seropositive patients with myasthenia gravis. Neurology 2000; 54: 474–479.Google Scholar
Baraka A, Haroun-Bizri S, Kawas N, Hajjar AM, Kawkabani N. Rocuronium in the myasthenic patient [Letter]. Anaesthesia 1995; 50: 1007.Google Scholar
Paterson IG, Hood JR, Russell SH, Weston MD, Hirsch NP. Mivacurium in the myasthenic patient. Br J Anaesth 1994; 73: 494–498.Google Scholar
Seigne RD, Scott RP. Mivacurium chloride and myasthenia gravis. Br J Anaesth 1994; 72: 468–469.Google Scholar
Baraka A. Anaesthesia and myasthenia gravis. Can J Anaesth 1992; 39: 476–486.Google Scholar
Buzello W, Noeldge G, Krieg N, Brobmann GF. Vecuronium for muscle relaxation in patients with myasthenia gravis. Anesthesiology 1986; 64: 507–509.Google Scholar
Baraka A, Taha S, Yazbeck V, Rizkallah P. Vecuronium block in the myasthenic patient. Influence of anticholinesterase therapy. Anaesthesia 1993; 48: 588–590.Google Scholar
Baraka A. Onset of neuromuscular block in myasthenic patients. Br J Anaesth 1992; 69: 227–228.Google Scholar
Huang YG, Luo AL, Luo LK. Evaluation of atracurium in myasthenic patients undergoing thymectomy. Proc Chin Acad Med Sci Peking Union Med Coll 1990; 5: 102–106.Google Scholar
Sanfilippo M, Fierro G, Cavalletti MV, Biancari F, Vilardi V. Rocuronium in two myasthenic patients undergoing thymectomy. Acta Anaesthesiol Scand 1997; 41: 1365–1366.Google Scholar
Hunter JM, Bell CF, Florence AM, Jones RS, Utting JE. Vecuronium in the myasthenic patient. Anaesthesia 1985; 40: 848–853.Google Scholar
Nilsson E, Meretoja OA. Vecuronium dose–response and maintenance requirements in patients with myasthenia gravis. Anesthesiology 1990; 73: 28–32.Google Scholar