Influences of neuromuscular blockers on vagal control of heart rate

Neuromuscular blocking drugs (NMBs) inhibit nicotinic acetylcholine receptors at the skeletal neuromuscular junction. These drugs are used during surgery to facilitate mechanical ventilation and the application of continuous paralysis. Nicotinic acetylcholine receptors are also located within autonomic ganglia and NMBs may therefore influence both sympathetic and parasympathetic (vagal) control of the cardiovascular system. Given the use of these drugs in research to facilitate the study of the cardiovascular system, our objective was to examine 3 different NMBs: pancuronium and rocuronium (aminosteroidal nondepolarizing NMBs) and cisatracurium (a benzylisoquinoline nondepolarizing NMB) on vagal control of heart rate (HR). Adult urethane (1.3 g/kg i.p) anaesthetised Lewis rats (n=6 rats per group), were instrumented to record blood pressure and HR and a sympathetic β-blocker atenolol (1 mg/kg i.v) was administered to inhibit sympathetic control of HR. Rats then received (i) pancuronium [bolus dose (2 mg/kg) then continuous infusion (1 mg/kg/hr)], (ii) rocuronium [bolus dose (12 mg/kg) and continuous infusion (10 mg/kg/hr)] or (iii) cisatracurium [(6 mg/kg) followed by continuous infusion (6 mg/kg/hr)] and changes in HR, mean arterial pressure (MAP) and baroreceptor reflex sensitivity (BRS), measured as change in HR evoked in response to phenylephrine (50 μg/kg) increase in MAP, assessed. None of the NMBs altered MAP. Cisatracurium and rocuronium had no effect on HR, whereas pancuronium increased HR (276.9±8.35 vs 365.3±12.91, P<0.05). BRS was reduced by pancuronium and rocuronium but not cisatracurium. Furthermore, when neuromuscular blockade was achieved with pancuronium, BRS was lower than when rocuronium or cisatracurium were used (0.25±0.02 vs 0.68±0.11 and 0.69±0.10 pm/mm Hg, respectively, p<0.05). These results indicate that cisatracurium has the least inhibitory effect on vagal control of HR. Future studies will investigate if the cardiac vagal protective effects of cisatracurium are preserved under different anaesthetic conditions, therefore providing information as to the best anaesthetic-NMB combination in which to investigate vagal control of HR.