KINETIC-ANALYSIS OF NEUROMUSCULAR BLOCKADE .1. RELATIONSHIP BETWEEN TWITCH DEPRESSION AND STIMULATION FREQUENCY AFTER D-TUBOCURARINE ADMINISTRATION

The degree of twitch depression induced by nondepolarizing neuromuscul ar blocking drugs is known to be dependent on the stimulation frequenc y employed. Train-of-four (TOF) stimulations with different frequencie s (0.67, 1.33 and 2.0 Hz) were delivered to a sciatic nerve of a rat a nd series of four twitch heights of a tibialis anterior muscle were me asured after d-tubocurarine (d-TC) administration. With a decrease of stimulus interval, twitch heights were intensely depressed. We hypothe sized that the oservations are due to the changes of released amount o f neuromuscular transmitter, acetylcholine, dependent on stimulus inte rval, and a pharmacokinetic/pharmacodynamic model based on the hypothe sis was proposed. The model allowed simultaneous fitting of the twitch height depression after d-TC administration. It also could give a rat ionale to the fact that TOF stimulation at 2.0 Hz is a more sensitive monitoring method of neuromuscular function than single twitch stimula tion (0.1-0.2 Hz).