Mechanisms Underlying the Vecuronium‐Induced Tetanic Fade in the Isolated Rat Muscle

Oliveira, Mário J. de; Oliveira, A. C. B. de

doi:10.1111/j.1600-0773.1999.tb02023.x

Cited by 10 publications

(17 citation statements)

References 33 publications

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“…The descending tension is termed TF. Possible mechanisms of TF include depressing ACh mobilization during tetanic stimulation [11], reducing the mean length of time that the AChR-ion channel complex is open by blocking the open ion channels [2,15], and decreasing the available AChRs by occlusion and desensitization [16]. …”

Section: Discussionmentioning

confidence: 99%

Do bupivacaine, clindamycin, and gentamicin at their clinical concentrations enhance rocuronium-induced neuromuscular block?

Lee

Park

et al. 2013

Korean J Anesthesiol

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BackgroundBupivacaine, clindamycin, and gentamicin inhibit neuromuscular (NM) conduction. When they are combined, they may synergistically reduce the effective concentration of each to the therapeutic concentration in augmenting rocuronium-induced NM block. Thus, the aim of this study was to investigate whether combinations of the three drugs, at around their therapeutic concentrations, potentiate rocuronium-induced NM block.MethodsFifty-seven left-phrenic nerve hemidiaphragms (Male S-D rats, 150-250 g) were hung in a 20-ml organ bath filled with Krebs solution. Three consecutive single-twitch tensions (0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained. A Krebs solution was premixed with concentration sets of bupivacaine and clindamycin, bupivacaine and gentamicin, or bupivacaine, clindamycin and gentamicin. Then, the concentration of rocuronium was cumulatively increased in the Krebs solution (1, 3, 5, 7, 9, 12, 14, 16, 18, and 20 µM) until an 80% to 90% reduction in single twitch was attained. The effective concentrations for each experiment were determined with the probit model.ResultsThe combinations of bupivacaine, clindamycin, and gentamicin enhanced rocuronium-induced NM block. When the three drugs were applied simultaneously, their concentrations were reduced to near-therapeutic levels in potentiating the action of rocuronium.ConclusionsBupivacaine, clindamycin, and gentamicin blocked NM conduction, and when all three drugs were applied together, they augmented rocuronium-induced NM block at their near-therapeutic concentrations. Clinicians should be aware of the cooperability in NM block between drugs that interrupt NM conduction.

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Section: Discussionmentioning

confidence: 99%

Do bupivacaine, clindamycin, and gentamicin at their clinical concentrations enhance rocuronium-induced neuromuscular block?

Lee

Park

et al. 2013

Korean J Anesthesiol

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“…At this point, it is interesting to compare these atracurium data with those corresponding to other neuromuscular blockers previously studied in this laboratory: hexamethonium (Gallacci & Oliveira 1990), pancuronium (Gallacci & Oliveira 1994) and vecuronium (de Oliveira & Oliveira 1999). All of them induced fade of tetanic contraction via a summation of pre‐ and postsynaptic effects.…”

Section: Discussionmentioning

confidence: 99%

“…This permitted us to compare atracurium, with regard to cellular mechanisms underlying the fade of the tetanic contraction, with a number of different blockers of neuromuscular transmission which have been previously studied in this laboratory: hexamethonium (Gallacci & Oliveira 1990), pancuronium(Gallacci & Oliveira 1994) and vecuronium(de Oliveira & Oliveira 1999). This comparison is important since we have demonstrated that the cellular mechanisms underlying the effect of these agents on the tetanic contraction differ from compound to compound(Gallacci & Oliveira 1990 & 1994; de Oliveira & Oliveira 1999). In the case of hexamethonium a postsynaptic blocking effect was the main cause of the tetanic fade (Gallacci & Oliveira 1990) while regarding pancuronium (Gallacci & Oliveira 1994) and vecuronium (de Oliveira & Oliveira 1999) both induced fade of tetanic contraction via a summation of pre‐ and postsynaptic blocking effects that were not as different in potency, as they were in the case of hexamethonium (Gallacci & Oliveira 1990).…”

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confidence: 99%

“…This comparison is important since we have demonstrated that the cellular mechanisms underlying the effect of these agents on the tetanic contraction differ from compound to compound(Gallacci & Oliveira 1990 & 1994; de Oliveira & Oliveira 1999). In the case of hexamethonium a postsynaptic blocking effect was the main cause of the tetanic fade (Gallacci & Oliveira 1990) while regarding pancuronium (Gallacci & Oliveira 1994) and vecuronium (de Oliveira & Oliveira 1999) both induced fade of tetanic contraction via a summation of pre‐ and postsynaptic blocking effects that were not as different in potency, as they were in the case of hexamethonium (Gallacci & Oliveira 1990).…”

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confidence: 99%

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Cellular Mechanisms of Atracurium‐Induced Tetanic Fade in the Isolated Rat Muscle

Nascimento

Serra

Oliveira

2004

Basic Clin Pharma Tox

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Although atracurium is a widely used neuromuscular blocker, we still lack knowledge regarding some of its cellular mechanisms of action. Thus, similar to other clinically used blockers atracurium induces, both in vivo and in vitro, fade of the tetanic contraction. However, the cellular mechanisms underlying this tetanic fade have never been systematically studied. In the present work these mechanisms were investigated in vitro. A sciatic nerve extensor digitorum longus muscle preparation of the rat was used. A combination of myographical and electrophysiological techniques was employed. Indirect twitches were evoked at 0.1 Hz and tetanic contractions at 50 Hz. Trains of end-plate potentials were evoked at a frequency of 50 Hz. The electrophysiological variables used in the analysis of the trains of end-plate potentials were: peak amplitude of the first end-plate potential in the train, peak amplitude of plateau end-plate potentials in the train, tetanic run-down of the end-plate potentials' train, quantal content of first and plateau end-plate potentials in the train, quantal size. In the myographical study atracurium, at a concentration of 2.4 mM, induced a complete fade of the tetanic contraction while only slightly affected the twitch. In the electrophysiological study atracurium, at the same 2.4 mM concentration, significantly decreased the amplitude of both first end-plate potentials in the train (control: 14.4 mV; atracurium: 3.2 mV) and plateau end-plate potentials (control: 10.8 mV; atracurium: 2.4 mV) and reinforced the tetanic run-down of the train of end-plate potentials, evaluated as the percent loss in amplitude of plateau end-plate potentials compared to first end-plate potentials in the trains (control: 25.2%; atracurium: 33.2%). Atracurium also significantly decreased the quantal content of first end-plate potentials in the train (control: 231; atracurium: 68), the quantal content of plateau end-plate potentials (control: 159; atracurium: 42) and the quantal size (control: 0.119 mV; atracurium: 0.075 mV). In relative terms the decrease in quantal content was about twice as large as the decrease in quantal size. This indicates that the fade of the tetanic contraction induced by atracurium (2.4 mM) is due to both pre-and postsynaptic blocking effects, the presynaptic one being stronger.

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“…These two compounds had their cellular effects scrutinized, in this laboratory, using electrophysiological techniques and were found to display differential effects at the neuromuscular junction [14,15]. These two compounds had their cellular effects scrutinized, in this laboratory, using electrophysiological techniques and were found to display differential effects at the neuromuscular junction [14,15].…”

Section: Discussionmentioning

confidence: 99%

Differential effects of neuromuscular blockers on twitches and tetani in the isolated rat muscle: a multiple comparison study using simultaneous confidence intervals

Ching

Serra

Nascimento

et al. 2008

Fundamemntal Clinical Pharma

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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.

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Mechanisms Underlying the Vecuronium‐Induced Tetanic Fade in the Isolated Rat Muscle

Cited by 10 publications

References 33 publications

Do bupivacaine, clindamycin, and gentamicin at their clinical concentrations enhance rocuronium-induced neuromuscular block?

Do bupivacaine, clindamycin, and gentamicin at their clinical concentrations enhance rocuronium-induced neuromuscular block?

Cellular Mechanisms of Atracurium‐Induced Tetanic Fade in the Isolated Rat Muscle

Differential effects of neuromuscular blockers on twitches and tetani in the isolated rat muscle: a multiple comparison study using simultaneous confidence intervals

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