Neuromuscular interactions between mivacurium and esmolol in rabbits

Abstract

SummaryWe compared the dose-response relationship and the neuromuscular blocking effects of mivacurium during infusions of esmolol in 40 anaesthetised rabbits. Train-of-four stimuli were applied every 10 s to the common peroneal nerve and the force of contraction of the tibialis anterior muscle was measured. Plasma cholinesterase activity decreased by 13% after esmolol infusion. .min ¹1, respectively (p < 0.001). The duration of neuromuscular block with mivacurium 0.16 mg.kg ¹1 was prolonged by 30% with esmolol due to diminished plasma cholinesterase activity (p < 0.05). Heart rate and mean arterial blood pressure decreased by 15% with esmolol (p < 0.05). The results of this study show that, in rabbits, esmolol decreased plasma cholinesterase activity, antagonised the neuromuscular blocking potency of mivacurium and prolonged its neuromuscular blocking effect. Esmolol is a water-soluble, cardioselective b-adrenoceptor antagonist with a rapid onset and ultrashort duration of action due to its short elimination half-life of 9 min [1]. As an ester it is rapidly metabolised by esterases in the blood to a free acid metabolite which has a b-adrenergic blocking potency 1/1600 that of the parent drug. The hydrolysis reaction occurs mainly in the cytosol of red blood cells but not in plasma [2]. Esmolol is widely used as a treatment for various cardiovascular diseases, including supraventricular tachyarrhythmias, hypertension and angina pectoris [3].Mivacurium is a nondepolarising muscle relaxant which has recently been introduced into clinical practice. Although chemically related to atracurium, it has a shorter duration of action [4,5]. It is hydrolysed by plasma cholinesterase in vitro at 70-88% the rate of suxamethonium [6][7][8]. Esmolol is reported to inhibit human plasma cholinesterase activity by 50% in vitro [9]. There are no 'in vivo' reports of pharmacological interactions between esmolol and mivacurium. The present study was undertaken to compare the dose-response relationships and the neuromuscular blocking effects of mivacurium during infusions of esmolol in anaesthetised rabbits. Method

Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

“…Given the intimate relationship between synaptic function, muscle activity, and muscle trophicity, it is unlikely that these factors can be fully separated. However, the effects of beta-blockers on muscle fatigue (14) and anesthesia (15) suggest that an important component of sympathetic activity affects synaptic integrity and function.…”

The pharmacodynamics of mivacurium in the rabbit with carbon tetrachloride-induced liver disease

“…This study would suggest, however, that neuromuscular block produced by mivacurium was not potentiated in spite of the reduced cholinesterase activity to about 70% in mild hepatitis (251.2 6 22.1 IU L 21 ). Plasma cholinesterase activity in rabbits is reported as approximately 20% of that in human beings [22,23]. Plasma cholinesterase activity in liver cirrhosis was reduced to 1/4 of that in the normal human being [24].…”

Interação funcional entre o sistema colinérgico e adrenérgico na manutenção da massa muscular e da placa motora

“…Next, we addressed the expression pattern of β 2 -AR in hindlimb muscle. This showed immunohistochemical signals of β 2 -AR in at least four different locations: (1) larger blood vessels (not depicted), (2) motoneurons (Figures 5A,B), (3) muscle fibers ( Figure 5E, left panel), and (4) ill-defined anastomotic fibers ( Figure 5E, on left panel see central part of the picture). Since the presence of β 2 -AR had been found by staining and anticipated to be present due to functional roles in blood vessels (Daly and McGrath, 2011), motoneurons (Melamed et al, 1976;Wohlberg et al, 1986;Bondok et al, 1988;Adachi et al, 1992;Parkis et al, 1995;Zeman et al, 2004;Tartas et al, 2010;Noga et al, 2011;Baker and Baker, 2012) and muscle fibers (Gross et al, 1976;Cairns and Dulhunty, 1993a,b;Cairns et al, 1993;Kokate et al, 1993;Navegantes et al, 1999Navegantes et al, , 2000Navegantes et al, , 2001Navegantes et al, , 2002Navegantes et al, , 2003Navegantes et al, , 2004Prakash et al, 1999;Decostre et al, 2000;Gonçalves et al, 2012), our findings in wildtype muscles were corroborating previous reports.…”