RESUMO
In the present work a comparative quantitative evaluation of the differential effects of neuromuscular blockers on twitches and tetani was performed, encompassing: atracurium, cisatracurium, mivacurium, pancuronium, rocuronium and vecuronium. The sciatic nerve-extensor digitorum longus muscle of the rat was used, in vitro. Twitches were evoked at 0.1 Hz and tetani at 50 Hz. The differential effects of the studied compounds on twitches and tetani were statistically compared using simultaneous confidence intervals for the ratios between mean IC(50) for the block of twitches and mean IC(50) for the block of tetani. The results of ratios of mean IC(50) together with their corresponding 95% simultaneous confidence intervals were: vecuronium: 2.5 (1.8-3.5); mivacurium: 3.8 (3.0-4.9); pancuronium: 3.9 (2.0-7.6); rocuronium: 6.1 (3.8-9.9); atracurium: 9.0 (6.4-12.6); cisatracurium: 13.1 (6.0-28.4). Using the criteria that neuromuscular blockers displaying disjunct confidence intervals for the ratios of mean IC(50) differ statistically with regard to differential effects on twitches and tetani, significant differences in ratios of IC(50) were detected in the following cases: vecuronium vs. rocuronium, vs. atracurium and vs. cisatracurium and mivacurium vs: cisatracurium and vs. atracurium. The results show that the magnitude of the differential effects of neuromuscular blockers on twitches and tetani, as evaluated in the present work in the form of ratios of mean IC(50), does not depend on the chemical structure (comparing steroidal and isoquinolinic compounds), but seems to depend on differential pre- and post-synaptic effects of the compounds. It is also suggested that the greater the ability of a compound to block twitches and tetani in a differential manner, the safer is the compound from the clinical anesthesiology viewpoint.
Assuntos
Músculo Esquelético/efeitos dos fármacos , Bloqueadores Neuromusculares/uso terapêutico , Tetania/prevenção & controle , Animais , Intervalos de Confiança , Feminino , Técnicas In Vitro , Masculino , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Bloqueadores Neuromusculares/farmacologia , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/fisiologia , Ratos , Ratos Wistar , Espasmo/fisiopatologia , Espasmo/prevenção & controle , Tetania/fisiopatologiaRESUMO
In the present work a comparative quantitative evaluation of the differential effects of neuromuscular blockers on twitches and tetani was performed, encompassing atracurium, cisatracurium, mivacurium, pancuronium, rocuronium and vecuronium. The sciatic nerve-extensor digitorum longus muscle of the rat was used, in vitro. Twitches were evoked at 0.1 Hz and tetani at 50 Hz. The differential effects of the studied compounds on twitches and tetani were statistically compared using simultaneous confidence intervals for the ratios between mean IC(50) for the block of twitches and mean IC(50) for the block of tetani. The results of ratios of mean IC(50) together with their corresponding 95% simultaneous confidence intervals were vecuronium 2.5 (1.8-3.5); mivacurium 3.8 (3.0-4.9); pancuronium 3.9 (2.0-7.6); rocuronium 6.1 (3.8-9.9); atracurium 9.0 (6.4-12.6); cisatracurium 13.1 (6.0-28.4). Using the criteria that neuromuscular blockers displaying disjunct confidence intervals for the ratios of mean IC(50) differ statistically with regard to differential effects on twitches and tetani, significant differences in ratios of IC(50) were detected in the following cases vecuronium vs. rocuronium, vs. atracurium and vs. cisatracurium and mivacurium vs cisatracurium and vs. atracurium. The results show that the magnitude of the differential effects of neuromuscular blockers on twitches and tetani, as evaluated in the present work in the form of ratios of mean IC(50), does not depend on the chemical structure (comparing steroidal and isoquinolinic compounds), but seems to depend on differential pre- and post-synaptic effects of the compounds. It is also suggested that the greater the ability of a compound to block twitches and tetani in a differential manner, the safer is the compound from the clinical anesthesiology viewpoint.
Assuntos
Animais , Masculino , Feminino , Ratos , Espasmo , Tetania/prevenção & controle , Técnicas In Vitro , Intervalos de Confiança , Ratos Wistar , Músculo Esquelético , Contração Muscular , Bloqueadores Neuromusculares , Junção NeuromuscularRESUMO
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.