Sympathomimetic Effects of Pancuronium Bromide on the Cardiovascular System of the Pithed Rat: A Comparison With the Effects of Drugs Blocking the Neuronal Uptake of Noradrenaline

Abstract

I The effects of pancuronium bromide on the cardiovascular system of the pithed rat were examined. Pancuronium had two effects, a short-lasting cardiovascular stimulation following injection and a longer-lasting potentiation of responses to sympathetic nerve stimulation. 2 The initial effect of pancuronium was compared with that of tyramine. The cardioaccelerator but not the pressor responses to both pancuronium and tyramine were significantly reduced following sympathectomy with 6-hydroxydopamine (6-OHDA). 3 The action of pancuronium in potentiating sympathetic nerve responses was compared with that of known blockers of the neuronal uptake of noradrenaline (NA). Pancuronium (1 mg/kg) and cocaine (0.5 mg/kg) potentiated cardioaccelerator and pressor responses to sympathetic stimulation. These effects of pancuronium could be obtained following adrenalectomy and during neuromuscular blockade with gallamine. Pancuronium and uptake blockers potentiated the cardioaccelerator response to NA, reduced the response to tyramine, but did not affect the response to isoprenaline. Pancuronium and uptake blockers potentiated the pressor response to NA, but did not affect the response to tyramine or clonidine. 4 Following sympathectomy with 6-OHDA, pancuronium failed to potentiate cardioaccelerator and pressor responses to NA. 5 These results are discussed in relation to two main cardiovascular effects of pancuronium; an indirect sympathomimetic action and blockade of the neuronal uptake of NA.

Comparison of the Pharmacology of Vecuronium and Atracurium with That of Other Currently Available Muscle Relaxants

“…Pancuronium and gallamine frequently increase heart rate and blood pressure. These changes are explained by cardiac antimuscarinic effects (vagolysis) and sympathetic nervous system stimulation (catecholamine release) following doses adequate to produce skeletal muscle relaxation during surgery (3,4). The hemodynamic changes following d-tubocurarine, pancuronium, gallamine, and occasionally metocurine occur because the muscle-relaxing dose range overlaps the dose range associated with blockade of vagal or sympathetic ganglionic transmission or with histamine release (Fig.…”

Analysis of the α‐adrenoceptor‐mediated, and other, components in the sympathetic vasopressor responses of the pithed rat

“…With this short pulse duration, neuromuscular blockade was not necessary because skeletal muscle twitching was acceptably small. The analysis of sympathetic responses was, therefore, free from the autonomic side-effects associated with muscle relaxants (Docherty & McGrath, 1978). Vascular reactivity was assessed as changes in diastolic blood pressure.…”

“…Chemical sympathectomy was achieved by pretreating rats with 6-hydroxydopamine (6-OHDA) before pithing: intraperitoneal injections, 2 x 50 mg kg-' on day 1, 2 x I00 mg kg-I on day 4, rats pithed on day 5 or 6 (Thoenen & Tranzer, 1968;Docherty & McGrath, 1978) 6-OHDA was dissolved in de-oxygenated 0.9% w/v NaCl solution (saline) containing ascorbic acid (1 mg kg-').…”

Cervicothoracic epidural anaesthesia blunts pancuronium‐induced increase in heart rate in humans

“…A high level of sympathectomy induced by cervico-thoracic epidural blockade can interrupt sympathetic effects to the heart (10, 1 l ) , while parasympathetic reflexes remain intact. Docherty & McGrath (8) reported that the cardioaccelerator response to pancuronium was reduced following pharmacological sympathectomy with 5-hydroxydopamine in rats, confirming indirect sympathomimetic action of pancuronium.…”