Yolanda Christina S. Loyola

Influence of Local Anesthetics on the Neuromuscular Blockade Produced by Rocuronium. Effects of Lidocaine and 50% Enantiomeric Excess Bupivacaine on the Neuromuscular Junction

BACKGROUND AND OBJECTIVES The effects of local anesthetics (LA) on neuromuscular transmission and their influence on the neuromuscular blockade produced by competitive neuromuscular blockers have not been fully investigated. The objective of this study was to evaluate, in vitro, the effects of lidocaine and 50% enantiomeric excess bupivacaine (S75-R25) on the neuromuscular blockade produced by rocuronium. METHODS The rats were divided in five groups (n = 5) according to the drug used: isolated lidocaine, bupivacaine (S75-R25), or rocuronium (groups I, II, and II); and rocuronium in preparations previously exposed to LAs (groups IV and V). The concentrations used were as follows: 20 microg x mL(-1), 5 microg x mL(-1), and 4 microg x mL(-1) of lidocaine, bupivacaine (S75-R25), and rocuronium, respectively. The following parameters were evaluated: 1) the strength of muscular contraction of the diaphragm to indirect electrical stimulations, before and 60 minutes after the isolated addition of the LAs and rocuronium, and the association AL-rocuronium; and 2) the effects of LAs on membrane potential (MP) and miniature end-plate potentials (MEPP). The effect of LAs on muscle contraction in response to acetylcholine was evaluated in chick biventer cervicis preparations. RESULTS Isolated lidocaine and bupivacaine (S75-R25) did not change the muscular response and the levels of MPs. In preparations exposed to LAs, rocuroniuminduced blockade was significantly greater than that produced by rocuronium alone. In chick biventer cervicis preparations, lidocaine and bupivacaine (S75R25) decreased contraction in response to acetylcholine. Lidocaine increased the frequency of MEPPs, which was followed by the blockade; bupivacaine (S75R25) caused a reduction in MEPPs followed by blockade. CONCLUSIONS Local anesthetics caused a potentiation of the neuromuscular blockade produced by rocuronium. The results showed pre- and post-synaptic effects.

Influência de anestésicos locais sobre o bloqueio neuromuscular produzido pelo rocurônio: ação da lidocaína e da mistura enantiomérica em excesso de 50% de bupivacaína na junção neuromuscular

JUSTIFICATIVA Y OBJETIVOS: Los efectos de los anestesicos locales (AL), en la transmision neuromuscular y su influencia en el bloqueo neuromuscular producido por bloqueadores neuromusculares competitivos, todavia no se ha investigado lo suficiente. El objetivo del estudio, fue evaluar in vitro los efectos de la lidocaina y de la mezcla enantiomerica en exceso de 50% de bupivacaina (S75-R25) en el bloqueo neuromuscular producido por el rocuronio. METODOS: Algunos ratones se distribuyeron en cinco grupos (n = 5) de acuerdo con el farmaco estudiado: lidocaina, bupivacaina (S75-R25), rocuronio, aisladamente (Grupos I, II, III); rocuronio en preparaciones previamente expuestas a los AL (Grupos IV, V). Las concentraciones utilizadas fueron: 20 µg.mL-1, 5 µg.mL-1 y 4 µg.mL-1, para lidocaina, bupivacaina (S75-R25), y rocuronio, respectivamente. Se evaluo: 1) la fuerza de contraccion muscular del diafragma a la estimulacion electrica indirecta, antes y 60 minutos despues de la adicion de los AL y rocuronio aisladamente, y la asociacion AL - rocuronio; 2) efectos de los AL sobre el potencial de la membrana (PM) y potenciales de placa terminal en miniatura (PPTM). En una preparacion biventer cervicis de pollito, se evaluo el efecto de los AL en la respuesta de contraccion a la acetilcolina. RESULTADOS: La lidocaina y la bupivacaina (S75-R25) aisladamente, no alteraron las respuestas musculares y los valores del PM. En las preparaciones expuestas a los AL, el bloqueo por el rocuronio fue significativamente mayor con relacion al producido por el rocuronio aisladamente. En una preparacion biventer cervicis de pollito, la lidocaina y la bupivacaina (S75-R25), redujeron la respuesta de contraccion a la acetilcolina. La lidocaina aumento la frecuencia de los PPTM, seguido de bloqueo; la bupivacaina (S75-R25) genero una disminucion seguida de bloqueo. CONCLUSIONES: Los anestesicos locales potenciaron el bloqueo neuromuscular causado por el rocuronio. Los resultados mostraron una accion presinaptica y postsinaptica.

Influence of lidocaine on the neuromuscular block produced by rocuronium: study in rat phrenic-diaphragmatic nerve preparation

BACKGROUND AND OBJECTIVES: The action mechanism of local anesthetics (LA) on neuromuscular junction motivated several studies. When administered at low doses, they do not interfere on neuromuscular transmission. But high doses may compromise neuromuscular transmission and increase the effects of neuromuscular blockers. The objective of this study was to evaluate lidocaine interaction with rocuronium on rat diaphragm through its influence on neuromuscular block degree. METHODS: Rats, weighing between 250 and 300 g, were used. Preparation was set according to the technique described by Bulbring. Groups were formed (n = 5) according to the drug being studied: lidocaine - 20 µg.mL-1 (Group I); rocuronium - 4 µg.mL-1 (Group II), and rocuronium - 4 µg.mL-1 with lidocaine - 20 µg.mL-1 (Group III). The following items were assessed: 1) the extent of diaphragm muscle responses to indirect stimulation, both before and 60 minutes after adding lidocaine and a neuromuscular blocker; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP); 3) the effectiveness of neostigmine, and 4) aminopyridine on neuromuscular blockage reversal. RESULTS: When administered separately, lidocaine did not alter the extent of muscular responses. With the previous use of lidocaine, rocuronium neuromuscular blockage was 82.8% ± 1.91%, with a significant difference (p = 0.0079) when compared to the group with isolated rocuronium (57.8% ± 1.9%). Blockage was both partially and fully reverted by neostigmine and 4-aminopyridine, respectively. Lidocaine did not alter membrane potential and caused an initial increase on MEPP, followed by a blockage. CONCLUSIONS: Lidocaine increases the neuromuscular blocking produced by rocuronium. MEPP modifications identify a presynaptic action. The complete antagonism of 4-aminopyridine indicates a presynaptic component. This idea is supported by the partial antagonism through neostigmine.BACKGROUND AND OBJECTIVES The action mechanism of local anesthetics (LA) on neuromuscular junction motivated several studies. When administered at low doses, they do not interfere on neuromuscular transmission. But high doses may compromise neuromuscular transmission and increase the effects of neuromuscular blockers. The objective of this study was to evaluate lidocaine interaction with rocuronium on rat diaphragm through its influence on neuromuscular block degree. METHODS Rats, weighing between 250 and 300 g, were used. Preparation was set according to the technique described by Bulbring. Groups were formed (n = 5) according to the drug being studied: lidocaine - 20 microg.mL-1 (Group I); rocuronium - 4 microg.mL-1 (Group II), and rocuronium - 4 microg.mL-1 with lidocaine - 20 microg.mL-1 (Group III). The following items were assessed: 1) the extent of diaphragm muscle responses to indirect stimulation, both before and 60 minutes after adding lidocaine and a neuromuscular blocker; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP); 3) the effectiveness of neostigmine, and 4) aminopyridine on neuromuscular blockage reversal. RESULTS When administered separately, lidocaine did not alter the extent of muscular responses. With the previous use of lidocaine, rocuronium neuromuscular blockage was 82.8% +/- 1.91%, with a significant difference (p = 0.0079) when compared to the group with isolated rocuronium (57.8% +/- 1.9%). Blockage was both partially and fully reverted by neostigmine and 4-aminopyridine, respectively. Lidocaine did not alter membrane potential and caused an initial increase on MEPP, followed by a blockage. CONCLUSIONS Lidocaine increases the neuromuscular blocking produced by rocuronium. MEPP modifications identify a presynaptic action. The complete antagonism of 4-aminopyridine indicates a presynaptic component. This idea is supported by the partial antagonism through neostigmine.

Influência da procainamida sobre o bloqueio neuromuscular produzido pelo rocurônio e investigação sobre o mecanismo de ação da procainamida na junção neuromuscular

BACKGROUND AND OBJECTIVES It has already been proved that procainamide potentiates the neuromuscular blockade of d-tubocurarine; however, the mechanism of this potentiation is controversial. The aim of this study was to assess the influence of procainamide on the neuromuscular blockade produced by rocuronium and investigate the mechanisms of this interaction. METHODS Fifteen rats (250 to 300 g) were used in the preparation described by Bülbring. They were divided in three groups (n = 5 each): procainamide - 20 microg mL(-1) (Group I); rocuronium - 4 microg mL(-1) (Group II); and rocuronium - 4 microg mL(-1) and procainamide - 20 microg mL(-1) (Group III). The following parameters were evaluated: 1) amplitude of muscle contractions under indirect stimulation, before and after the administration of the drugs; 2) miniature end plate potentials (MEPPs); and 3) the efficacy of 4-aminopyridine in reverting the muscular blockade. The mechanism of the interaction was studied in Biventer cervicis (n = 5) and in the denervated rat diaphragm (n = 5), observing the influence of procainamide in the response to acetylcholine. RESULTS Procainamide alone did not change the neuromuscular responses. Group III presented a 68.6% +/- 7.1% blockade, which represented a statistically significant difference (p = 0.0067) when compared with Group II (10.4% +/- 4.5%), which was reverted by 4-aminopiridine. Procainamide increased the frequency of the MEPP, followed by a blockade that was reverted by 4-aminopiridine. In Biventer cervicis, procainamide increased the contraction in response to acetylcholine, which was not observed in the denervated diaphragm. CONCLUSIONS Procainamide potentiated the blockade caused by rocuronium. The changes observed with MEPP and Biventer cervicis identified pre-synaptic action. The antagonism of 4-aminopiridine on the blockade of the MEPP suggested receptor desensitization by procainamide.JUSTIFICATIVA Y OBJETIVOS: La potenciacion de la procainamida sobre el bloqueo neuromuscular producido por la d-tubocurarina ya esta comprobada, pero sin embargo el mecanismo es controvertido. El objetivo del estudio fue el de evaluar la influencia de la procainamida en el bloqueo neuromuscular producido por el rocuronio e investigar los mecanismos de esa interaccion. METODO: Se utilizaron 15 ratones (250 a 300 g) en preparacion descrita por Bulbring. Se formaron los siguientes grupos (n = 5 cada): procainamida - 20 µg.mL-1 (Grupo I); rocuronio - 4 µg.mL-1 (Grupo II) y rocuronio - 4µg.mL-1 y procainamida - 20µg.mL-1 (Grupo III). Se evaluo: 1) la amplitud de las contracciones musculares bajo la estimulacion indirecta en cada grupo, antes y despues de la adicion de los farmacos; 2) los potenciales de placa terminal en miniatura (PPTM); 3) la eficacia de la 4-aminopiridina en la reversion del bloqueo neuromuscular. El mecanismo de la interaccion se estudio en Biventer cervicis (n = 5) y diafragma de raton desnervado (n = 5), observandose la influencia de la procainamida en la respuesta a la acetilcolina antes y despues de la adicion de la procainamida. RESULTADOS: De forma aislada, la procainamida no altero las respuestas neuromusculares. El bloqueo producido con el Grupo III fue de 68,6% ± 7,1%, con una diferencia significativa (p = 0,0067) con relacion al Grupo II (10,4% ± 4,5%), revertido por la 4-aminopiridina. La procainamida ocasiono un aumento en la frecuencia de los PPTM, seguido de bloqueo revertido por la 4-aminopiridina. En Biventer cervicis, la procainamida aumento la respuesta a la accion de contraccion de la acetilcolina, resultado no observado con el diafragma desnervado. CONCLUSIONES: La procainamida potencio el bloqueo producido por el rocuronio. Las alteraciones observadas con PPTM y Biventer cervicis identificaron una accion presinaptica. El antagonismo de la 4-aminopiridina sobre el bloqueo de los PPTMs sugirio la desensibilizacion de los receptores por la procainamida.

Influence of nifedipine on the neuromuscular block produced by atracurium and cistracurium: study in rat phrenic-diaphragmatic nerve preparation

BACKGROUND AND OBJECTIVES Calcium channel blockers may interact with neuromuscular blockers, increasing its effects. Research studies about this interaction display controversial results. In some studies these drugs produced neuromuscular blockage, or contracture, or no effect at all was proved over skeletal neuromuscular response. This study assessed the nifedipine effects over muscular responses and its possible interaction with neuromuscular blockers in rat diaphragm. METHODS A number of 25 rats were used, weighing between 250 and 300 g and sacrificed under anesthesia with intraperitoneal pentobarbital (40 mg.kg-1). Preparation was mounted according to the technique described by Bulbring. Diaphragm was kept under tension, connected to an isometric transducer and subjected to an indirect stimulation of 0.1 Hz frequency. Diaphragm contractions were registered on a physiograph. In order to evaluate the effect of these drugs on neuromuscular transmission, they were added separately or associated to the preparation, on the following concentrations: nifedipine (4 microg.mL-1); atracurium (20 microg.mL-1); cistracurium (3 microg.mL-1). On phrenic-nerve preparation, the assessed items were: 1) the extent of diaphragm muscle response to indirect stimulation, before and 45 minutes after adding nifedipine and neuromuscular blockers separately and after the association of both drugs; 2) nifedipine effects on membrane potentials (MP) and miniature end-plate potentials (MEPP). RESULTS Employed separately, nifedipine did not alter the extent of muscular responses, but it did significantly increase the neuromuscular blocking activity of atracurium and cistracurium. Nifedipine did not alter the membrane potential and caused an initial increase on MEPP frequencies, followed by a blockage. CONCLUSIONS Nifedipine, on the employed concentration, increased the neuromuscular blockage produced by atracurium and cistracurium. Electrophysiological studies demonstrate the existence of presynaptic action and absence of depolarizing action over the muscle fiber.

Influência do lítio no bloqueio neuromuscular produzido pelo atracúrio e pelo cisatracúrio: estudo em preparações nervo frênico-diafragma de rato

JUSTIFICATIVA Y OBJETIVOS: El litio, farmaco ampliamente utilizado en los disturbios bipolares, puede interactuar con los bloqueadores neuromusculares. Los mecanismos para explicar sus efectos en la transmision neuromuscular y en la interaccion con bloqueadores neuromusculares son controvertidos. El objetivo de este trabajo fue evaluar, en diafragma de raton, los efectos del litio sobre la respuesta muscular al estimulo indirecto y la posible interaccion con los bloqueadores neuromusculares. METODO: Se utilizaron ratones con peso entre 250 y 300 g, sacrificados bajo anestesia con uretana. La preparacion nervio frenico-diafragma se monto de acuerdo con la tecnica de Bulbring. El diafragma se mantuvo bajo tension, ligado a un transductor isometrico y sometido a la estimulacion indirecta de 0,1 Hz de frecuencia. Las contracciones del diafragma fueron registradas en un fisiografo. Del analisis de la amplitud de las respuestas musculares se evaluaron los efectos de los farmacos: litio (1,5 mg.mL-1); atracurio (20 µg.mL-1) y cisatracurio (3 µg.mL-1) empleados aisladamente; de la asociacion litio-bloqueadores neuromusculares; y del litio en el bloqueo neuromuscular producido por el atracurio (35 µg.mL-1) y cisatracurio (5 µg.mL-1). Los efectos se evaluaron antes y 45 minutos despues de la adicion de los farmacos. Tambien se estudiaron los efectos del litio en los potenciales de membrana (PM) y potenciales de placa terminal en miniatura (PPTM). RESULTADOS: El litio aisladamente no altero la amplitud de las respuestas musculares, pero si que redujo significativamente el bloqueo neuromuscular producido por el atracurio y el cisatracurio. No altero el PM y ocasiono un aumento inicial de la frecuencia de los PPTM. CONCLUSIONES: El litio empleado aisladamente no comprometio la transmision neuromuscular y aumento la resistencia al efecto del atracurio y del cisatracurio. No mostro accion sobre la fibra muscular, siendo que las alteraciones en los potenciales de placa terminal en miniatura mostraron una accion presinaptica.BACKGROUND AND OBJECTIVES Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL-1); atracurium (20 microg.mL-1), and cisatracurium (3 microg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 microg.mL-1) and cisatracurium (5 microg.mL-1). The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP) and miniature end-plate potentials (MEPP) were also evaluated. RESULTS Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials indicated pre-synaptic action.

Influence of lithium on the neuromuscular blockade produced by atracurium and cisatracurium: study on rat phrenic nerve-diaphragm preparations

JUSTIFICATIVA Y OBJETIVOS: El litio, farmaco ampliamente utilizado en los disturbios bipolares, puede interactuar con los bloqueadores neuromusculares. Los mecanismos para explicar sus efectos en la transmision neuromuscular y en la interaccion con bloqueadores neuromusculares son controvertidos. El objetivo de este trabajo fue evaluar, en diafragma de raton, los efectos del litio sobre la respuesta muscular al estimulo indirecto y la posible interaccion con los bloqueadores neuromusculares. METODO: Se utilizaron ratones con peso entre 250 y 300 g, sacrificados bajo anestesia con uretana. La preparacion nervio frenico-diafragma se monto de acuerdo con la tecnica de Bulbring. El diafragma se mantuvo bajo tension, ligado a un transductor isometrico y sometido a la estimulacion indirecta de 0,1 Hz de frecuencia. Las contracciones del diafragma fueron registradas en un fisiografo. Del analisis de la amplitud de las respuestas musculares se evaluaron los efectos de los farmacos: litio (1,5 mg.mL-1); atracurio (20 µg.mL-1) y cisatracurio (3 µg.mL-1) empleados aisladamente; de la asociacion litio-bloqueadores neuromusculares; y del litio en el bloqueo neuromuscular producido por el atracurio (35 µg.mL-1) y cisatracurio (5 µg.mL-1). Los efectos se evaluaron antes y 45 minutos despues de la adicion de los farmacos. Tambien se estudiaron los efectos del litio en los potenciales de membrana (PM) y potenciales de placa terminal en miniatura (PPTM). RESULTADOS: El litio aisladamente no altero la amplitud de las respuestas musculares, pero si que redujo significativamente el bloqueo neuromuscular producido por el atracurio y el cisatracurio. No altero el PM y ocasiono un aumento inicial de la frecuencia de los PPTM. CONCLUSIONES: El litio empleado aisladamente no comprometio la transmision neuromuscular y aumento la resistencia al efecto del atracurio y del cisatracurio. No mostro accion sobre la fibra muscular, siendo que las alteraciones en los potenciales de placa terminal en miniatura mostraron una accion presinaptica.BACKGROUND AND OBJECTIVES Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL-1); atracurium (20 microg.mL-1), and cisatracurium (3 microg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 microg.mL-1) and cisatracurium (5 microg.mL-1). The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP) and miniature end-plate potentials (MEPP) were also evaluated. RESULTS Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials indicated pre-synaptic action.

Influence of procainamide on the neuromuscular blockade caused by rocuronium and investigation on the mechanism of action of procainamide on the neuromuscular junction

BACKGROUND AND OBJECTIVES It has already been proved that procainamide potentiates the neuromuscular blockade of d-tubocurarine; however, the mechanism of this potentiation is controversial. The aim of this study was to assess the influence of procainamide on the neuromuscular blockade produced by rocuronium and investigate the mechanisms of this interaction. METHODS Fifteen rats (250 to 300 g) were used in the preparation described by Bülbring. They were divided in three groups (n = 5 each): procainamide - 20 microg mL(-1) (Group I); rocuronium - 4 microg mL(-1) (Group II); and rocuronium - 4 microg mL(-1) and procainamide - 20 microg mL(-1) (Group III). The following parameters were evaluated: 1) amplitude of muscle contractions under indirect stimulation, before and after the administration of the drugs; 2) miniature end plate potentials (MEPPs); and 3) the efficacy of 4-aminopyridine in reverting the muscular blockade. The mechanism of the interaction was studied in Biventer cervicis (n = 5) and in the denervated rat diaphragm (n = 5), observing the influence of procainamide in the response to acetylcholine. RESULTS Procainamide alone did not change the neuromuscular responses. Group III presented a 68.6% +/- 7.1% blockade, which represented a statistically significant difference (p = 0.0067) when compared with Group II (10.4% +/- 4.5%), which was reverted by 4-aminopiridine. Procainamide increased the frequency of the MEPP, followed by a blockade that was reverted by 4-aminopiridine. In Biventer cervicis, procainamide increased the contraction in response to acetylcholine, which was not observed in the denervated diaphragm. CONCLUSIONS Procainamide potentiated the blockade caused by rocuronium. The changes observed with MEPP and Biventer cervicis identified pre-synaptic action. The antagonism of 4-aminopiridine on the blockade of the MEPP suggested receptor desensitization by procainamide.JUSTIFICATIVA Y OBJETIVOS: La potenciacion de la procainamida sobre el bloqueo neuromuscular producido por la d-tubocurarina ya esta comprobada, pero sin embargo el mecanismo es controvertido. El objetivo del estudio fue el de evaluar la influencia de la procainamida en el bloqueo neuromuscular producido por el rocuronio e investigar los mecanismos de esa interaccion. METODO: Se utilizaron 15 ratones (250 a 300 g) en preparacion descrita por Bulbring. Se formaron los siguientes grupos (n = 5 cada): procainamida - 20 µg.mL-1 (Grupo I); rocuronio - 4 µg.mL-1 (Grupo II) y rocuronio - 4µg.mL-1 y procainamida - 20µg.mL-1 (Grupo III). Se evaluo: 1) la amplitud de las contracciones musculares bajo la estimulacion indirecta en cada grupo, antes y despues de la adicion de los farmacos; 2) los potenciales de placa terminal en miniatura (PPTM); 3) la eficacia de la 4-aminopiridina en la reversion del bloqueo neuromuscular. El mecanismo de la interaccion se estudio en Biventer cervicis (n = 5) y diafragma de raton desnervado (n = 5), observandose la influencia de la procainamida en la respuesta a la acetilcolina antes y despues de la adicion de la procainamida. RESULTADOS: De forma aislada, la procainamida no altero las respuestas neuromusculares. El bloqueo producido con el Grupo III fue de 68,6% ± 7,1%, con una diferencia significativa (p = 0,0067) con relacion al Grupo II (10,4% ± 4,5%), revertido por la 4-aminopiridina. La procainamida ocasiono un aumento en la frecuencia de los PPTM, seguido de bloqueo revertido por la 4-aminopiridina. En Biventer cervicis, la procainamida aumento la respuesta a la accion de contraccion de la acetilcolina, resultado no observado con el diafragma desnervado. CONCLUSIONES: La procainamida potencio el bloqueo producido por el rocuronio. Las alteraciones observadas con PPTM y Biventer cervicis identificaron una accion presinaptica. El antagonismo de la 4-aminopiridina sobre el bloqueo de los PPTMs sugirio la desensibilizacion de los receptores por la procainamida.

Influencia del litio en el bloqueo neuromuscular producido por el atracurio y por el cisatracurio: estudio en preparo nervio frénico-diafragma del ratón

JUSTIFICATIVA Y OBJETIVOS: El litio, farmaco ampliamente utilizado en los disturbios bipolares, puede interactuar con los bloqueadores neuromusculares. Los mecanismos para explicar sus efectos en la transmision neuromuscular y en la interaccion con bloqueadores neuromusculares son controvertidos. El objetivo de este trabajo fue evaluar, en diafragma de raton, los efectos del litio sobre la respuesta muscular al estimulo indirecto y la posible interaccion con los bloqueadores neuromusculares. METODO: Se utilizaron ratones con peso entre 250 y 300 g, sacrificados bajo anestesia con uretana. La preparacion nervio frenico-diafragma se monto de acuerdo con la tecnica de Bulbring. El diafragma se mantuvo bajo tension, ligado a un transductor isometrico y sometido a la estimulacion indirecta de 0,1 Hz de frecuencia. Las contracciones del diafragma fueron registradas en un fisiografo. Del analisis de la amplitud de las respuestas musculares se evaluaron los efectos de los farmacos: litio (1,5 mg.mL-1); atracurio (20 µg.mL-1) y cisatracurio (3 µg.mL-1) empleados aisladamente; de la asociacion litio-bloqueadores neuromusculares; y del litio en el bloqueo neuromuscular producido por el atracurio (35 µg.mL-1) y cisatracurio (5 µg.mL-1). Los efectos se evaluaron antes y 45 minutos despues de la adicion de los farmacos. Tambien se estudiaron los efectos del litio en los potenciales de membrana (PM) y potenciales de placa terminal en miniatura (PPTM). RESULTADOS: El litio aisladamente no altero la amplitud de las respuestas musculares, pero si que redujo significativamente el bloqueo neuromuscular producido por el atracurio y el cisatracurio. No altero el PM y ocasiono un aumento inicial de la frecuencia de los PPTM. CONCLUSIONES: El litio empleado aisladamente no comprometio la transmision neuromuscular y aumento la resistencia al efecto del atracurio y del cisatracurio. No mostro accion sobre la fibra muscular, siendo que las alteraciones en los potenciales de placa terminal en miniatura mostraron una accion presinaptica.BACKGROUND AND OBJECTIVES Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL-1); atracurium (20 microg.mL-1), and cisatracurium (3 microg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 microg.mL-1) and cisatracurium (5 microg.mL-1). The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP) and miniature end-plate potentials (MEPP) were also evaluated. RESULTS Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials indicated pre-synaptic action.

Influencia de la procainamida sobre el bloqueo neuromuscular producido por el rocuronio e investigación sobre el mecanismo de acción de la procainamida en la junción neuromuscular

BACKGROUND AND OBJECTIVES It has already been proved that procainamide potentiates the neuromuscular blockade of d-tubocurarine; however, the mechanism of this potentiation is controversial. The aim of this study was to assess the influence of procainamide on the neuromuscular blockade produced by rocuronium and investigate the mechanisms of this interaction. METHODS Fifteen rats (250 to 300 g) were used in the preparation described by Bülbring. They were divided in three groups (n = 5 each): procainamide - 20 microg mL(-1) (Group I); rocuronium - 4 microg mL(-1) (Group II); and rocuronium - 4 microg mL(-1) and procainamide - 20 microg mL(-1) (Group III). The following parameters were evaluated: 1) amplitude of muscle contractions under indirect stimulation, before and after the administration of the drugs; 2) miniature end plate potentials (MEPPs); and 3) the efficacy of 4-aminopyridine in reverting the muscular blockade. The mechanism of the interaction was studied in Biventer cervicis (n = 5) and in the denervated rat diaphragm (n = 5), observing the influence of procainamide in the response to acetylcholine. RESULTS Procainamide alone did not change the neuromuscular responses. Group III presented a 68.6% +/- 7.1% blockade, which represented a statistically significant difference (p = 0.0067) when compared with Group II (10.4% +/- 4.5%), which was reverted by 4-aminopiridine. Procainamide increased the frequency of the MEPP, followed by a blockade that was reverted by 4-aminopiridine. In Biventer cervicis, procainamide increased the contraction in response to acetylcholine, which was not observed in the denervated diaphragm. CONCLUSIONS Procainamide potentiated the blockade caused by rocuronium. The changes observed with MEPP and Biventer cervicis identified pre-synaptic action. The antagonism of 4-aminopiridine on the blockade of the MEPP suggested receptor desensitization by procainamide.JUSTIFICATIVA Y OBJETIVOS: La potenciacion de la procainamida sobre el bloqueo neuromuscular producido por la d-tubocurarina ya esta comprobada, pero sin embargo el mecanismo es controvertido. El objetivo del estudio fue el de evaluar la influencia de la procainamida en el bloqueo neuromuscular producido por el rocuronio e investigar los mecanismos de esa interaccion. METODO: Se utilizaron 15 ratones (250 a 300 g) en preparacion descrita por Bulbring. Se formaron los siguientes grupos (n = 5 cada): procainamida - 20 µg.mL-1 (Grupo I); rocuronio - 4 µg.mL-1 (Grupo II) y rocuronio - 4µg.mL-1 y procainamida - 20µg.mL-1 (Grupo III). Se evaluo: 1) la amplitud de las contracciones musculares bajo la estimulacion indirecta en cada grupo, antes y despues de la adicion de los farmacos; 2) los potenciales de placa terminal en miniatura (PPTM); 3) la eficacia de la 4-aminopiridina en la reversion del bloqueo neuromuscular. El mecanismo de la interaccion se estudio en Biventer cervicis (n = 5) y diafragma de raton desnervado (n = 5), observandose la influencia de la procainamida en la respuesta a la acetilcolina antes y despues de la adicion de la procainamida. RESULTADOS: De forma aislada, la procainamida no altero las respuestas neuromusculares. El bloqueo producido con el Grupo III fue de 68,6% ± 7,1%, con una diferencia significativa (p = 0,0067) con relacion al Grupo II (10,4% ± 4,5%), revertido por la 4-aminopiridina. La procainamida ocasiono un aumento en la frecuencia de los PPTM, seguido de bloqueo revertido por la 4-aminopiridina. En Biventer cervicis, la procainamida aumento la respuesta a la accion de contraccion de la acetilcolina, resultado no observado con el diafragma desnervado. CONCLUSIONES: La procainamida potencio el bloqueo producido por el rocuronio. Las alteraciones observadas con PPTM y Biventer cervicis identificaron una accion presinaptica. El antagonismo de la 4-aminopiridina sobre el bloqueo de los PPTMs sugirio la desensibilizacion de los receptores por la procainamida.