title: Denervation stage differentially influences resistance to neuromuscular blockers in rat gastrocnemius.
abstract: BACKGROUND
  Muscle denervation was common in clinical surgery patients, which was mostly caused by trauma, paraplegia, and other factors. Denervated muscle in patients could lead to significant differential reaction to neuromuscle blockers due to the time of denervation and affected muscle area. We tested the hypothesis that resistance to non-depolarizing muscle relaxants (NDMRs) changes with time, and is related to the expression of immature and total acetylcholine receptors (AChRs).
  
  
  METHODS
  The study evaluated the effect change of neuromuscular blockers in tibial nerve transected rat model. To determine 50% effective dose of NDMRs and succinycholine at 1, 7, 14, 28, and 35 days after denervation, action potential amplitude was monitorted by intracellular recording method. The messenger DNA that encodes the AChR-γ and AChR-ε subunits and the protein of the -γ and -ε subunits were quantified in the gastrocnemius by reverse transcription-polymerase chain reaction and western blotting respectively. Receptor number and pharmacodynamic changes was analyzed by correlation and regression analysis.
  
  
  RESULTS
  Increased AChR-γ correlated with total AChRs, suggesting that the up-regulated AChRs may contain the immature isoform. The 50% effective dose of vecuronium and atracurium increased 1.2- to 1.5-fold at all time periods and correlated significantly with AChRs and AChR-γ.
  
  
  CONCLUSIONS
  After denervation, resistance to NDMRs occurred earlier, was more marked from 14 days, and changes in resistance to NDMRs in skeletal muscle after nerve injury is dependent on the level of expression of immature and total AChRs. Denervation time should be of concern when such patients undergo surgery.
authors.affiliation: Department of Anesthesiology, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Jiang
authors.forename: Ya-Chun
authors.initials: YC
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shi-Tong
authors.initials: ST
authors.lastname: Li
mesh_terms: D000818:Animals; D001279:Atracurium / Q000494:pharmacology; D004351:Drug Resistance; D008297:Male; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000187:drug effects*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000235:genetics; D013997:Time Factors; D014673:Vecuronium Bromide / Q000494:pharmacology
chemical_list: D009466:Neuromuscular Blocking Agents; D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D001279:Atracurium; D014673:Vecuronium Bromide