The influence of stimulation parameters on the potency and reversibility of neuromuscular blocking agents

Abstract

Voluntary muscle movements in mammalian muscles are initiated by short trains of 16 to 60 Hz impulses (Zierler, 1974). Despite this in most neurophysiological and neuropharmacological studies either single stimuli of 0.1 to 2 Hz or 5 to 10 sec 50 to 500 Hz tetani have been employed. Neither of these two types of stimuli are ideal for the testing of the functional integrity of the motor unit. Stimulation with single impulses, at slow rates, does not reveal incipient pathological or drug induced defects. Recovery of neuromuscular (NM) activity after 5 to 10 sec tetanic stimulation is prolonged and after repeated stimulation of this type the preparations decay rapidly. Stimulation of 0.1 sec trains of 50 Hz impulses applied every 10 to 20 sec eliminate the above disadvantages. This type of stimulation represents adequate challenge for revealing more moderate degrees of functional defects of the myoneural apparatus without causing rapid decay of the in vitro or in vivo preparations. In agreement with this the ED50 of NM blocking agents were found to be significantly lower in both the in vitro phrenic nerve-hemidiaphragm preparation and the in vivo sciatic nervetibialis anterior muscle preparation of rats during stimulation with 0.1 sec trains of 50 Hz impulses, than when single stimuli of 0.1 Hz were used. Recovery of the in vitro preparations after washout or in vivo after discontinuation of the infusion was also slower during stimulation with short trains of tetani. The antagonist potency of anticholinesterases or 4-aminopyridine and maximal recovery after the use of the optimal concentrations of these antagonists was less in the preparations stimulated with short trains of tetani than in those stimulated with single impulses.

Tubocurarine and Pancuronium Inhibit Evoked Release of Acetylcholine From the Mouse Hemidiaphragm Preparation

“…However, the finding (table II) that the threshold concentrations of neuromuscular blockers required to decrease the evoked release of acetylcholine and tetanic fade were slightly less than those that inhibited peak tetanic tension and tetanic fade indicate that even a marginal decrease of acetylcholine release might affect the integrity of neuromuscular transmission at higher stimulation rates. Decrease of the evoked release of acetylcholine per stimulus (volley output of acetylcholine) during tetanic stimulation was observed in both neurophysiological (Liley and North, 1953) and neurochemical (Foldes et al, 1978) studies. The prejunctional inhibition of evoked release of acetylcholine by neuromuscular blockers is also involved in the production of tetanic fade, train-of-four fade and tetanic reduction of EPP.…”

“…This assumption is supported by findings in laboratory animals and by clinical observations. Thus, for example, the blocking potency of non-depolarizing neuromuscular blocking drugs and aminoglycoside-or polypeptide-type antibiotics is much greater in in vivo and in vitro nervemuscle preparations stimulated with short trains of 50-Hz tetani than in those stimulated with single impulses at 0.1 Hz (Foldes, Chaudhry et al, 1981). In anaesthetized patients recovering from the effects of non-depolarizing neuromuscular blockade, at the time when the twitch tension elicited by single impulses (at 0.1 Hz) had returned to or above 95 % of control, the T4/T1 ratio was only 0.55 (Foldes, Yun et al, 1981).…”