Antifibrillatory properties of mivacurium in a canine model of atrial fibrillation.
The electrophysiologic actions of the competitive neuromuscular blocker mivacurium (0.05-0.8 mg/kg IV; N = 10) and atropine sulfate [0.01-0.16 mg/Kg intravenously (IV), N = 6] were determined under control conditions, during right vagus nerve stimulation, and during anterior right ganglionated plexus stimulation. Both drugs suppressed shortening of right atrial monophasic action potential (MAP) duration, right atrial refractoriness, and right superior pulmonary vein sleeve refractoriness produced by vagus nerve or ganglionated plexus stimulation and suppressed the induction of atrial fibrillation. Suppression of atrial fibrillation by atropine was accompanied by improved sinus and atrioventricular (AV) nodal function, increasing the ventricular heart rate observed during sinus rhythm and atrial fibrillation and eliminating the depressant actions of vagus nerve stimulation on sinoatrial (SA) and AV nodal function. Unlike atropine, mivacurium selectively antagonized the effects of vagus nerve and ganglionated plexus stimulation on atrial and pulmonary vein sleeve myocardium (shortening of action potential duration/refractoriness and increased atrial vulnerability) without altering sinus or AV nodal function under control conditions or during vagus nerve stimulation. The selective inhibition of parasympathetic nervous system effects in atrium versus sinus and AV nodes by mivacurium may represent a selective mechanism for the suppression of atrial fibrillation without altering SA and AV nodal function.
Patterson
Eugene
E
University of Oklahoma Health Sciences Center, OU Medical Center, Oklahoma City, Oklahoma, USA. eugene-patterson@ouhsc.edu
Lu
Zhibing
Z
Lin
Jiaxiong
J
Scherlag
Benjamin J
BJ
Po
Sunny S
SS
Coscia
Daniel
D
Lazzara
Ralph
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001283:Atrioventricular Node / Q000187:drug effects / Q000503:physiopathology; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D000077590:Mivacurium; D003473:Neuromuscular Nondepolarizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010276:Parasympatholytics / Q000008:administration & dosage / Q000494:pharmacology; D012849:Sinoatrial Node / Q000187:drug effects / Q000503:physiopathology; D014630:Vagus Nerve / Q000378:metabolism
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D010276:Parasympatholytics; D000077590:Mivacurium; D001285:Atropine