Cisatracurium: myographical and electrophysiological studies in the isolated rat muscle

Abstract

Myographical and electrophysiological studies of cisatracurium were performed, in vitro, in the isolated sciatic nerve-extensor digitorum longus muscle preparation of the rat. Indirect twitches were generated at 0.1 Hz and tetanic contractions at 50 Hz. endplate potentials (epps) were generated in trains of 50 Hz. The electrophysiological variables used in the analysis of the epps were: amplitude of the first epp in the train, average amplitude of the 30 degrees to the 59 degrees epp in the train (epps-plateau), tetanic rundown (percent loss in amplitude of epps-plateau relative to the first epp in the train), quantal size and quantal content. The myographical results showed that the inhibitory concentration 50% (IC(50)) of cisatracurium for the blockade of twitches (0.48 microm) is 12 times its IC(50) for the induction of tetanic fade (0.04 microm). The electrophysiological results showed a concentration dependent decrease in the amplitudes of first epps in the trains and of epps-plateau in the two used concentrations (0.13 microm and 0.38 microm). The tetanic rundown was intensified only in the presence of the higher (0.38 microm) concentration of cisatracurium. In cisatracurium 0.13 microm (a concentration which affects only tetanic contractions, inducing their fade, while leaving the twitch unaffected) there was a decrease in the quantal content of the first epp and of epps-plateau in the train. In cisatracurium (0.38 microm), a concentration, which affects the twitch, there was a decrease of the quantal size and of quantal content of epps-plateau, but not of the quantal content of the first epp in the train. The results indicate that the fade of the tetanic contraction induced by cisatracurium at the concentration of 0.13 microm is entirely because of a pre-synaptic blocking effect while the decrease in the twitch induced by cisatracurium at the concentration of 0.38 microm is due to a post-synaptic blocking effect.