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Effects of presynaptic muscarinic cholinoreceptor blockade on neuromuscular transmission as assessed by the train‐of‐four and the tetanic fade response to rocuronium
Author(s) -
Kim Yong Beom,
Lee Sangseok,
Lee Kyeong Chun,
Kim Ha Jung,
Ro Young Jin,
Yang HongSeuk
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12763
Subject(s) - rocuronium , neuromuscular transmission , muscarinic acetylcholine receptor , pirenzepine , chemistry , fade , atropine , stimulation , endocrinology , neuromuscular monitoring , methoctramine , neuromuscular junction , medicine , anesthesia , neuromuscular blockade , receptor , biology , biochemistry , neuroscience , computer science , propofol , operating system
Summary This study investigated the effect of muscarinic M 1 and M 2 receptor 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 M 1 blocker) at concentrations of 0 nmol L −1 (control), 10 nmol L −1 ( PZP 10), or 100 nmol L −1 ( PZP 100). 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 M 2 receptor blocker, loaded at 0 μmol L −1 [control], 1 μmol L −1 [ MET 1], or 10 μmol L −1 [ MET 10]). The EC 95 of rocuronium was significantly lower in the PZP 10 group than in the control group. In the PZP 10 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 MET 10 group compared to the other groups. This study shows that antagonists of muscarinic M 1 and M 2 receptors affect the rocuronium‐induced neuromuscular block as demonstrated by the reduced EC 95 and TOF ratios (M 1 antagonist, pirenzepine) or the enhanced 50‐Hz tetanic fade (M 2 antagonist, methoctramine).