Neuromuscular blocking agents' differential bronchoconstrictive potential in Guinea pig airways.
BACKGROUND
Neuromuscular blocking agents are designed to antagonize nicotinic cholinergic receptors on skeletal muscle but also antagonize muscarinic receptors. Several muscle relaxants have the potential to promote bronchoconstriction due to unintended effects exemplified by histamine release of atracurium or mivacurium and detrimental interactions with muscarinic receptors by rapacuronium. Although interactions of muscle relaxants with muscarinic receptors have been extensively characterized in vitro, limited information is available on their potential interactions with airway tone in vivo.


METHODS
Changes in pulmonary inflation pressures and heart rates induced by vagal nerve stimulation and intravenous acetylcholine were measured in the absence and presence of increasing doses of gallamine, pancuronium, mivacurium, vecuronium, cisatracurium, rocuronium, or rapacuronium in guinea pigs. Mivacurium's and rapacuronium's potential of inducing bronchoconstriction by histamine release was also evaluated.


RESULTS
Rapacuronium potentiated both vagal nerve-stimulated and intravenous acetylcholine-induced increases in airway pressures, which were totally blocked by atropine but not pyrilamine. Vecuronium, rocuronium, mivacurium, and cisatracurium were devoid of significant airway effects. Mivacurium, at high doses, increased pulmonary inflation pressures, which were attenuated by pyrilamine.


CONCLUSIONS
Rapacuronium was unique among muscle relaxants evaluated in that it potentiated both vagal nerve- and intravenous acetylcholine-induced bronchoconstriction with no evidence of histamine release. The dual detrimental interactions of rapacuronium with muscarinic receptors previously demonstrated in vitro correlate with in vivo muscarinic receptor mechanisms of bronchoconstriction and may account for the profound bronchoconstriction seen with its clinical use. These findings may establish pharmacologic characteristics to avoid with new muscle relaxants intended for clinical use.
Jooste
Edmund
E
Department of Anesthesiology, Columbia University, New York, New York 10032, USA.
Zhang
Yi
Y
Emala
Charles W
CW
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D043643:Receptor, Muscarinic M1 / Q000187:drug effects; D043585:Receptor, Muscarinic M2 / Q000187:drug effects; D043587:Receptor, Muscarinic M3 / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
D009466:Neuromuscular Blocking Agents; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D000109:Acetylcholine