Antifibrillatory actions of cisatracurium: an atrial specific M2 receptor antagonist.
BACKGROUND
Muscarinic receptor antagonists are proposed to prevent atrial fibrillation (AF), but also facilitate AV conduction, limiting clinical usefulness.


METHODS
Cisatracurium, a neuromuscular blocker, was administered to anesthetized dogs (0.05-0.8 mg/kg IV) and was administered to superfused pulmonary vein (PV) tissues in vitro.


RESULTS
Dose-dependent suppression of AF induced by premature atrial stimuli was observed under control conditions (n = 3), right vagus nerve stimulation (n = 7), and anterior right ganglionated plexus stimulation (n = 3). AF was prevented (P < 0.0001) concurrent with suppression of the decreased atrial MAP duration/ERP accompanying vagus nerve stimulation without altering AH intervals or sinus cycle length. Although atropine (0.001-0.016 mg/kg, n = 4) suppressed AF (P < 0.04) in association with suppression of atrial MAP shortening induced by vagus nerve stimulation, atropine also prevented sinus cycle length and AH interval prolongation with vagus nerve stimulation, and decreased AV effective and functional refractory periods. In vitro, both cisatracurium and atropine prevented (1) action potential shortening produced by acetylcholine administration and (2) action potential shortening and arrhythmia triggering within PV sleeves produced by local autonomic nerve stimulation, atropine producing competitive inhibition, and cisatracurium producing noncompetitive M(2) muscarinic receptor blockade.


CONCLUSIONS
Cisatracurium demonstrates a dose-dependent (1) suppression of AF and atrial action potential shortening accompanying vagus nerve stimulation without facilitating sinus or atrioventricular nodal function and (2) noncompetitive blockade of action potential shortening and triggered firing induced in isolated PVs by local autonomic nerve stimulation. The data are consistent with allosteric binding of cisatracurium to the M(2) muscarinic receptor in canine atrium.
Patterson
Eugene
E
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA. eugene-patterson@ouhsc.edu
Scherlag
Benjamin J
BJ
Zhou
Jing
J
Jackman
Warren M
WM
Lazzara
Ralph
R
Coscia
Daniel
D
Po
Sunny
S
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001279:Atracurium / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001281:Atrial Fibrillation / Q000503:physiopathology* / Q000517:prevention & control*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000008:administration & dosage; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors*
D000889:Anti-Arrhythmia Agents; D009466:Neuromuscular Blocking Agents; D043585:Receptor, Muscarinic M2; D001279:Atracurium; C101584:cisatracurium