title: Synergistic effect of sevoflurane and isoflurane on inhibition of the adult-type muscle nicotinic acetylcholine receptor by rocuronium.
abstract: OBJECTIVE
  Inhaled anesthetics increase the incidence of postoperative residual neuromuscular blockade, and the mechanism is still unclear. We have investigated the synergistic effect of low-concentration inhaled anesthetics and rocuronium on inhibition of the inward current of the adult-type muscle nicotinic acetylcholine receptor (ε-nAChR).
  
  
  METHODS
  Adult-type mouse muscle ε-nAChR was expressed in HEK293 cells by liposome transfection. The inward current of the ε-nAChR was activated by use of 10 μmol/L acetylcholine alone or in combination with different concentrations of sevoflurane, isoflurane, or rocuronium. The concentration-response curves of five cells were constructed, and the data yielded the 5, 25, and 50 % inhibitory concentrations (IC5, IC25, and IC50, respectively) for single-drug application. Subsequently, the functional channels were perfused by adding 0.5 IC5 of either sevoflurane or isoflurane (aqueous concentrations 140 and 100 μmol/L, respectively) to the solution, followed by addition of IC5, IC25, or IC50 rocuronium. The amount of inhibition was calculated to quantify their synergistic effect.
  
  
  RESULTS
  The inhibitory effect of rocuronium was enhanced by sevoflurane or isoflurane in a concentration-dependent manner. Sevoflurane or isoflurane (0.5 IC5) with rocuronium at IC5, IC25, and IC50 synergistically inhibited the current amplitude of adult-type muscle ε-nAChR. When the IC5 of rocuronium was used, isoflurane had a stronger synergistic effect than sevoflurane (p < 0.05). When rocuronium was applied at higher concentrations (IC25 and IC50), sevoflurane had an effect similar to that of isoflurane. For both inhaled anesthetics, the synergistic effect was more intense for rocuronium at IC5 than for rocuronium at IC25 or IC50.
  
  
  CONCLUSIONS
  Residual-concentration sevoflurane or isoflurane has a strong synergistic effect with rocuronium at clinically relevant residual concentrations. A lower rocuronium concentration resulted in a stronger synergistic effect.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, Friendship Road #1, Yuan Jia Gang, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Wei
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Min
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D002460:Cell Line; D004357:Drug Synergism; D057809:HEK293 Cells; D006801:Humans; D007530:Isoflurane / Q000494:pharmacology*; D008738:Methyl Ethers / Q000494:pharmacology*; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D019148:Neuromuscular Blockade / Q000379:methods; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D000077123:Rocuronium; D000077149:Sevoflurane
chemical_list: D000732:Androstanols; D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D000077149:Sevoflurane; D007530:Isoflurane; D000109:Acetylcholine; D000077123:Rocuronium