Department of Anesthesiology, First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China.
Acta Pharmacol Sin. 2010 Dec;31(12):1541-6. doi: 10.1038/aps.2010.163. Epub 2010 Nov 22.
to investigate the changing resistance to nondepolarizing muscle relaxants (NDMRs) during the first month after denervation.
the denervated and innervated skeletal muscle cells were examined on days 1, 4, 7, 14, 21, and 28 after denervation. Individual denervated and innervated cells were prepared from the flexor digitorum brevis of the surgically denervated and contralateral hind feet, respectively. Nicotinic acetylcholine receptors (nAChRs) in the cells were activated with 30 micromol/L acetylcholine, either alone or in combination with various concentrations of vecuronium. Currents were recorded using a whole-cell patch-clamp technique.
the concentrations of vecuronium resulting in half-maximal inhibitory responses (IC(50)) increased 1.2- (P>0.05), 1.7-, 3.7-, 2.5-, 1.9-, and 1.8-fold (P<0.05) at Days 1, 4, 7, 14, 21, and 28 after denervation, respectively, compared to the innervated control. Resistance to vecuronium appeared at Day 4, peaked at Day 7, and declined at Day 14 after denervation. Nevertheless, IC(50) values at Day 28 remained significantly higher than those for the innervated control, suggesting that the resistance to vecuronium had not disappeared at Day 28.
The NDMR doses required to achieve satisfactory clinical effects differ at different times after muscle denervation.
研究去神经后第一个月非去极化肌松药(NDMRs)耐药性的变化。
在去神经后第 1、4、7、14、21 和 28 天,检查去神经和神经支配的骨骼肌细胞。分别从手术去神经的和对侧后脚的屈趾短肌中制备单个去神经和神经支配的细胞。用 30 μmol/L 乙酰胆碱单独或与不同浓度的维库溴铵联合激活细胞中的烟碱型乙酰胆碱受体(nAChRs)。使用全细胞膜片钳技术记录电流。
与神经支配的对照相比,去神经后第 1、4、7、14、21 和 28 天,维库溴铵产生半最大抑制反应(IC(50))的浓度分别增加了 1.2-(P>0.05)、1.7-、3.7-、2.5-、1.9-和 1.8 倍(P<0.05)。去神经后第 4 天出现维库溴铵耐药,第 7 天达到峰值,第 14 天下降。然而,第 28 天的 IC(50)值仍明显高于神经支配的对照,表明第 28 天维库溴铵的耐药性尚未消失。
在不同的去神经后时间,实现满意临床效果所需的 NDMR 剂量不同。