Effects of non-depolarizing neuromuscular blocking agents on norepinephrine release from human atrial tissue obtained during cardiac surgery

We have studied the effect of non-depolarizing neuromuscular blockingagents, at concentrations present in serum during anaesthesia, on releaseof [3H]-norepinephrine ([3H]NE) from superfused atrial appendage obtainedduring cardiac surgery from 48 patients. Three of the neuromuscularblocking agents (pancuronium, gallamine and rocuronium), which are known tocause an increase in heart rate during anaesthesia, increasedstimulation-evoked release of [3H]NE. In contrast, (+)tubocurarine andpipecuronium, neuromuscular blocking agents that do not cause tachycardia,did not affect release of NE. Org 9487 significantly enhanced release whileSZ1677 was ineffective, even at concentrations higher than those expectedafter administration of a 2 x ED95 dose. Atropine enhanced release. Thesedata suggest that the axon terminals of sympathetic nerves in human hearthave muscarinic heteroreceptors whose activation by acetylcholine (ACh)released from the vagal nerve reduces release of NE. This actioncontributes to lowering of heart rate. Therefore, any neuromuscularblocking agent with antimuscarinic actions and capable of increasing therelease of NE may produce tachycardia.