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

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.