Effect of Isoflurane and Sevoflurane on the Potencies of the Neuromuscular Blocking Agents in Rat in Vivo

Background Neuromuscular blocking agents induce muscle paralysis via the prevention of synaptic transmission at the neuromuscular junction and may have additional effects at other sites of action. With regard to potential effects of neuromuscular blocking agents on the central nervous system, a definitive view has not been established. We investigated whether intravenous infusion of rocuronium bromide affects the emergence from propofol anesthesia. Methods Using an in vivo rat model, we performed propofol infusion for 60 minutes, along with rocuronium bromide at various infusion rates or normal saline. Sugammadex or normal saline was injected at the end of the infusion period, and we evaluated the time to emergence from propofol anesthesia. We also examined the neuromuscular blocking, circulatory, and respiratory properties of propofol infusion along with rocuronium bromide infusion to ascertain possible factors affecting emergence. Results Intravenous infusion of rocuronium bromide dose-dependently increased the time to emergence from propofol anesthesia. Sugammadex administered after propofol infusion not containing rocuronium bromide did not affect the time to emergence. Mean arterial pressure, heart rate, partial pressures of oxygen and carbon dioxide, and pH were not affected by rocuronium bromide infusion. Neuromuscular blockade induced by rocuronium bromide, even at the greatest infusion rate in the emergence experiment, was rapidly antagonized by sugammadex. Conclusions These results suggest that intravenous infusion of rocuronium bromide dose-dependently delays the emergence from propofol anesthesia in rats. Future studies, such as detection of rocuronium in the cerebrospinal fluid or central nervous system, electrophysiologic studies, microinjection of sugammadex into the brain, etc., are necessary to determine the mechanism of this effect.

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Acyclic Cucurbit[n]uril-Type Molecular Containers Bind Neuromuscular Blocking Agents In Vitro and Reverse Neuromuscular Block In Vivo

Angewandte Chemie International Edition ◽

10.1002/anie.201206031 ◽

2012 ◽

Vol 51 (45) ◽

pp. 11358-11362 ◽

Cited By ~ 92

Author(s):

Da Ma ◽

Ben Zhang ◽

Ulrike Hoffmann ◽

Martina Grosse Sundrup ◽

Matthias Eikermann ◽

...

Keyword(s):

Neuromuscular Block ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agents ◽

Blocking Agents

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Acyclic Cucurbit[n]uril-Type Containers as Receptors for Neuromuscular Blocking Agents

Croatica Chemica Acta ◽

10.5562/cca3507 ◽

2019 ◽

Vol 92 (2) ◽

pp. 163-171

Author(s):

David Shaya ◽

Lyle Isaacs

Keyword(s):

Water Solubility ◽

Neuromuscular Block ◽

Binding Constants ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agents ◽

Optical Methods ◽

Titration Calorimetry ◽

Blocking Agents

Acyclic cucurbit[n]uril molecular containers 1 and 2C3 have previously been shown to strongly bind to the neuromuscular blocking agents rocuronium, vecuronium, pancuronium, and cisatracurium in vitro by optical methods and to reverse neuromuscular block in vivo in rats. In this paper we study the in vitro binding of a panel of acyclic CB[n]-type receptors toward the four neuromuscular blocking agents and acetylcholine to develop structure-binding affinity relationships. The selected variants include those with different aromatic sidewalls (e.g. 1Me4 with dimethyl o-xylylene walls; 3 with 1,8-linked naphthalene walls), with different glycoluril oligomer lengths (e.g. 4 and 5 based on glycoluril trimer), and with different linker lengths between aromatic wall and SO3- solubilizing group (e.g. 2C2–2C4). Based on the analysis of complexation induced changes in 1H NMR chemical shift we conclude that the hydrophobic regions of the guests bind in the hydrophobic cavity of the hosts with the cationic moieties of the guest binding at the ureidyl C=O portals by ion-dipole and ion-ion interactions. The thermodynamic parameters of binding were determined by direct and competition isothermal titration calorimetry experiments. We find that hosts 4 and 5 based on glycoluril trimer form significantly weaker complexes with the streroidal NMBAs than with the analogues hosts based on glycoluril tetramer (1 and 2C3). Similarly, hosts 1Me4 and 3 with different length and height aromatic walls do not exhibit the extreme binding constants displayed by 2C3 but rather behave similarly to 1. Finally, we find that hosts 2C2 and 2C4 bind only slightly more weakly to the NMBAs than 2C3, but retain the ability to discriminate against acetylcholine, and possess higher inherent water solubility than 2C3. Host 2C4, in particular, holds potential for future in vivo applications.

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Gantacurium and CW002 Do Not Potentiate Muscarinic Receptor-mediated Airway Smooth Muscle Constriction in Guinea Pigs

Anesthesiology ◽

10.1097/aln.0b013e3181d32016 ◽

2010 ◽

Vol 112 (4) ◽

pp. 892-899 ◽

Cited By ~ 11

Author(s):

Hiroshi Sunaga ◽

Yi Zhang ◽

John J. Savarese ◽

Charles W. Emala

Keyword(s):

Heart Rate ◽

Guinea Pig ◽

Muscarinic Receptors ◽

Guinea Pigs ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agents ◽

In Vivo Model ◽

Inflation Pressure ◽

Blocking Agents

Background Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors, undesirable airway effects (i.e., bronchoconstriction) can result from neuromuscular blocking agents' affinity for airway muscarinic receptors. We questioned whether two new members of a bisquaternary nondepolarizing muscle relaxant family, gantacurium and CW002, demonstrated detrimental effects of airway muscarinic receptors using an in vivo model in guinea pig airways. Methods Urethane-anesthetized male guinea pigs were ventilated through a tracheostomy with continuous digital recordings of pulmonary inflation pressure and heart rate. The dose for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium was defined in the guinea pig. Transient and reproducible changes in pulmonary inflation pressure and heart rate were recorded after vagal nerve stimulation or intravenous injection of acetylcholine before and after pretreatment with cumulatively increasing concentrations of gantacurium, CW002, cisatracurium or a single concentration of rapacuronium. Results The doses for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium were 0.064 +/- 0.006, 0.012 +/- 0.0006, 0.10 +/- 0.003, and 0.31 +/- 0.05 mg/kg, respectively. Gantacurium, CW002, and cisatracurium were without effects on baseline pulmonary inflation pressures and were devoid of significant interactions with M2 and M3 muscarinic receptors in vivo. Conclusion These findings suggest that gantacurium and CW002 are devoid of significant effects at airway muscarinic receptors particularly M3 receptors on bronchial smooth musculature at doses several fold higher than those required for functional muscle paralysis.

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DEPOLARIZING NEUROMUSCULAR BLOCKING AGENTS AND INTRAOCULAR PRESSURE IN VIVO

Anesthesiology ◽

10.1097/00000542-195705000-00008 ◽

1957 ◽

Vol 18 (3) ◽

pp. 439-442 ◽

Cited By ~ 9

Author(s):

JOHN B. DILLON ◽

PHIROZE SABAWALA ◽

DERMOT B. TAYLOR ◽

RALPH GUNTER

Keyword(s):

Intraocular Pressure ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agents ◽

Blocking Agents

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Neuromuscular Blocking Agents' Differential Bronchoconstrictive Potential in Guinea Pig Airways

Anesthesiology ◽

10.1097/01.anes.0000264763.48920.c9 ◽

2007 ◽

Vol 106 (4) ◽

pp. 763-772 ◽

Cited By ~ 27

Author(s):

Edmund Jooste ◽

Yi Zhang ◽

Charles W. Emala

Keyword(s):

Histamine Release ◽

Muscarinic Receptors ◽

Neuromuscular Blocking ◽

Muscle Relaxants ◽

Neuromuscular Blocking Agents ◽

Vagal Nerve ◽

Clinical Use ◽

Blocking Agents

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. Conclusion 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.

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