title: Neuromuscular blocking effects of cisatracurium and its antagonism with neostigmine in a canine model of autosomal-recessive centronuclear myopathy.
abstract: BACKGROUND
  Centronuclear myopathy (CNM) is a rare congenital condition associated with skeletal muscle weakness. Patients with CNM may have decreased acetylcholine receptor expression and a reduced number of releasable quanta. Such perturbations could affect the time-course of neuromuscular blocking agents (NMBAs) and their antagonism with cholinesterase inhibitors. As a result of the rarity of CNM, prospective data regarding NMBA use in this subpopulation is scarce. We evaluated the neuromuscular blocking effects of cisatracurium and its antagonism with neostigmine in a canine model of CNM.
  
  
  METHODS
  Six dogs with congenital autosomal-recessive CNM and six controls received cisatracurium 0.15 mg kg(-1) i.v. under general anaesthesia and intermittent positive pressure ventilation. Neuromuscular function was monitored with acceleromyography.When the second response (T2) to train-of-four (TOF) stimulation returned, neostigmine 0.04 mg kg(-1) (with glycopyrrolate) were administered i.v. The onset time, time to spontaneous return of T2, and the time to reach a TOF ratio ≥0.9 after neostigmine administration were recorded.
  
  
  RESULTS
  Onset time was no different between groups. Median (interquartile range) time to return of T2 was 27 (24-31) min for control dogs and 26 (22-31) min for CNM dogs (P=0.93).After neostigmine administration, a TOF ratio ≥0.9 was reached in 12 (10-15) min and 17 (16-19) min in control and CNM, respectively (P=0.005).
  
  
  CONCLUSIONS
  The spontaneous return of T2 was not different between groups. However, neostigmine-facilitated recovery was significantly slower in dogs with CNM. Canine autosomal-recessive CNM does not preclude the use of cisatracurium or its antagonism with neostigmine.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, USA martinflores@cornell.edu.
authors.forename: M
authors.initials: M
authors.lastname: Martin-Flores
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: Paré
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, USA.
authors.forename: L
authors.initials: L
authors.lastname: Campoy
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Gleed
mesh_terms: D000762:Anesthesia Recovery Period; D000768:Anesthesia, General / Q000379:methods; D000818:Animals; D001279:Atracurium / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D016343:Monitoring, Intraoperative / Q000379:methods; D020914:Myopathies, Structural, Congenital / Q000503:physiopathology*; D009388:Neostigmine / Q000494:pharmacology*; D019148:Neuromuscular Blockade / Q000379:methods; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D002800:Cholinesterase Inhibitors; D009466:Neuromuscular Blocking Agents; D001279:Atracurium; D009388:Neostigmine; C101584:cisatracurium
keywords: myotubular myopathy; neuromuscular nondepolarizing agents