De Haes A, Proost J H, De Baets M H, Stassen M H W, Houwertjes M C, Wierda J M K H
University Medical Center Groningen, Department of Anesthesiology, Groningen, The Netherlands.
Eur J Anaesthesiol. 2005 Aug;22(8):591-6. doi: 10.1017/s0265021505000992.
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.
Functional acetylcholine receptors were reduced by administration of alpha-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.
The potency of neuromuscular blocking agents was increased and the offset of the neuromuscular block was prolonged in both the alpha-bungarotoxin groups and the experimental autoimmune myasthenia gravis groups compared to controls.
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.
在重症肌无力患者中，非去极化神经肌肉阻滞剂的作用时间延长且敏感性增加。我们使用顺行灌注大鼠腓总神经 - 胫前肌模型来研究这种效应时间过程和敏感性的改变是否可以由该疾病导致的乙酰胆碱受体浓度降低来解释。
通过给予α - 银环蛇毒素或注射抗大鼠乙酰胆碱受体单克隆抗体（实验性自身免疫性重症肌无力）来减少功能性乙酰胆碱受体。诱导麻醉后，建立模型并开始用血液灌注胫前肌。在抽搐稳定后，输注罗库溴铵或泮库溴铵直至达到90%的阻滞。记录抽搐数据和输注数据，并用于计算效应时间过程和效价。
与对照组相比，α - 银环蛇毒素组和实验性自身免疫性重症肌无力组的神经肌肉阻滞剂效价均增加，神经肌肉阻滞的消退时间延长。
本研究表明，重症肌无力患者对神经肌肉阻滞剂敏感性增加可由乙酰胆碱受体数量减少来解释。它还表明，顺行灌注大鼠腓总神经 - 胫前肌模型是研究重症肌无力对神经肌肉阻滞剂效应时间过程影响的合适模型。
