title: Effects of presynaptic muscarinic cholinoreceptor blockade on neuromuscular transmission as assessed by the train-of-four and the tetanic fade response to rocuronium.
abstract: This study investigated the effect of muscarinic M1and M2receptor antagonists on the rocuronium-induced train of four (TOF) fade and tetanic fade, respectively. Ex-vivo phrenic nerves and diaphragms were obtained from adult Sprague-Dawley rats and stabilized in Krebs buffer; the nerve-stimulated muscle TOF fade was observed at 20 s intervals. For the TOF study, phrenic nerves and diaphragms were incubated with pirenzepine (an M1blocker) at concentrations of 0 nmol L-1(control), 10 nmol L-1(PZP10), or 100 nmol L-1(PZP100). Rocuronium was then administered incrementally until the first twitch tension had depressed by >95% during TOF stimulation. The mean TOF ratios were compared when the first twitch tensions were depressed by 40%-50%. For the tetanic fade study, 50 Hz/5 s tetani was applied initially, 30 min after the administration of a loading dose of rocuronium and methoctramine (an M2receptor blocker, loaded at 0 μmol L-1[control], 1 μmol L-1[MET1], or 10 μmol L-1[MET10]). The EC95of rocuronium was significantly lower in the PZP10 group than in the control group. In the PZP10 group, the TOF ratios at 50% and first twitch tension depression were significantly lower than those in the control group (P=.02). During tetanic stimulation, the tetanic fade was significantly enhanced in the MET10 group compared to the other groups. This study shows that antagonists of muscarinic M1and M2receptors affect the rocuronium-induced neuromuscular block as demonstrated by the reduced EC95and TOF ratios (M1antagonist, pirenzepine) or the enhanced 50-Hz tetanic fade (M2antagonist, methoctramine).
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Gil Medical Center, College of Medicine, Gachon University, Incheon, Korea.
authors.forename: Yong Beom
authors.identifier: http://orcid.org/0000-0003-2369-6525
authors.initials: YB
authors.lastname: Kim
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Sangye Paik Hospital, College of Medicine, Inje University, Seoul, Korea.
authors.forename: Sangseok
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Gil Medical Center, College of Medicine, Gachon University, Incheon, Korea.
authors.forename: Kyeong Chun
authors.initials: KC
authors.lastname: Lee
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
authors.forename: Ha Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Ro
authors.affiliation: Department of Anaesthesiology and Pain Medicine, Asan Medical Center, College of Medicine, Ulsan University, Seoul, Korea.
authors.forename: Hong-Seuk
authors.initials: HS
authors.lastname: Yang
mesh_terms: D000732:Androstanols / Q000494:pharmacology*; D000818:Animals; D003959:Diamines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D061886:Neuromuscular Monitoring; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors*; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors*; D012032:Refractory Period, Electrophysiological / Q000187:drug effects*; D000077123:Rocuronium; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000732:Androstanols; D003959:Diamines; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D010890:Pirenzepine; C054938:methoctramine; D000077123:Rocuronium
keywords: acetylcholine release; methoctramine; muscarinic cholinoreceptor; neuromuscular physiology; pirenzepine; rocuronium