title: Pharmacodynamic changes with vecuronium in sepsis are associated with expression of α7- and γ-nicotinic acetylcholine receptor in an experimental rat model of neuromyopathy.
abstract: BACKGROUND
  Resistance to non-depolarizing neuromuscular blocking agents induced by sepsis is associated with the qualitative change in the nicotinic acetylcholine receptor (nAChR). This study aims to investigate the effects of sepsis on the neuromuscular block properties of vecuronium in relation to the expression of fetal and neuronal α7 type nAChR.
  
  
  METHODS
  Male Sprague-Dawley rats were randomly divided into sham and sepsis groups. Sepsis was induced by caecal ligation and puncture (CLP). The rats were injected i.v. with ulinastatin or normal saline on Day 10. Neuromuscular block properties of vecuronium were evaluated and neuromuscular function was assessed by electromyography on Days 1, 3, 7, and 14 after CLP. Expression of fetal and neuronal type α7-nAChR on the tibialis anterior muscle was assessed using immunohistochemistry and western blot. The mRNA encoding for γ- and α7 subunits was evaluated by real-time polymerase chain reaction.
  
  
  RESULTS
  The half maximal inhibitory response of vecuronium in the sepsis group significantly increased, peaked on Day 7, and then declined on Day 14 (P<0.05). The neuromuscular function decreased with increasing postoperation time in the sepsis group (P<0.05). Sepsis significantly increased the expression of γ- and α7-nAchR along with expression of γ- and α7 subunits mRNA, peaked on Day 7, and declined on Day 14 (P<0.05). Ulinastatin suppressed the expression of receptor protein and mRNA encoding for γ- and α7 subunits (P<0.05).
  
  
  CONCLUSIONS
  Pharmacodynamic changes with vecuronium seem to be associated with the expression of γ- and α7-nAChR in the skeletal muscle. Ulinastatin can improve this effect by inhibiting the expression of these receptors.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Chongqing Medical University, You Yi Road 1#, Yuan Jia Gang, Chongqing 400016, China.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Min
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: K
authors.initials: K
authors.lastname: Wei
authors.forename: J
authors.initials: J
authors.lastname: Luo
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Ao
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009468:Neuromuscular Diseases / Q000188:drug therapy*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics*; D018805:Sepsis / Q000503:physiopathology*; D014673:Vecuronium Bromide / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: D006023:Glycoproteins; D003473:Neuromuscular Nondepolarizing Agents; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D014673:Vecuronium Bromide; C028665:urinastatin
keywords: neuromuscular blocking agents; pharmacology; receptors, nicotinic; sepsis 