Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/article/doi/10.1590/S0034-70942006000200007
Brazilian Journal of Anesthesiology
Scientific Article

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

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

Silmara Rodrigues de Sousa; Angélica de Fátima de Assunção Braga; Glória Maria Braga Potério; Franklin Sarmento da Silva Braga; Yolanda Christina S Loyola; Samanta Cristina Antoniassi Fernandes

http://dx.doi.org/10.1590/S0034-70942006000200007 Braz J Anesthesiol, vol.56, n2, p.157-167, 2006
PDF Português
PDF English
Downloads: 0
Views: 1097

Resumo

JUSTIFICATIVA E OBJETIVOS: Os bloqueadores de canais de cálcio podem interagir com bloqueadores neuromusculares potencializando seus efeitos. Os estudos sobre essa interação mostram resultados controversos. Em alguns estudos essas drogas produziram bloqueio neuromuscular, ou contratura, ou nenhum efeito sobre as respostas musculares esqueléticas foi evidenciado. O estudo avaliou, em diafragma de rato, os efeitos da nifedipina sobre a resposta muscular e sua possível interação com os bloqueadores neuromusculares. MÉTODO: Foram utilizados 25 ratos, com peso entre 250 e 300 g sacrificados sob anestesia com pentobarbital (40 mg.kg -1) por via intraperitonial. A preparação foi montada de acordo com a técnica descrita por Bulbring. O diafragma foi mantido sob tensão, ligado a um transdutor isométrico e submetido à estimulação indireta de 0,1 Hz de freqüência. As contrações do diafragma foram registradas em fisiógrafo. Para avaliação dos efeitos das drogas na transmissão neuromuscular, estas foram adicionadas isoladamente ou associadas à preparação, nas seguintes concentrações: nifedipina (4 µg.mL-1); atracúrio (20 µg.mL-1); cisatracúrio (3 µg.mL-1). Nas preparações nervo frênico-diafragma avaliaram-se: 1) a amplitude das respostas do músculo diafragma à estimulação indireta, antes e 45 minutos após a adição da nifedipina e dos bloqueadores neuromusculares isoladamente e após a associação das drogas; 2) os efeitos da nifedipina nos potenciais de membrana (PM) e potenciais de placa terminal em miniatura (PPTM). RESULTADOS: A nifedipina empregada isoladamente não alterou a amplitude das respostas musculares, mas aumentou significativamente a atividade bloqueadora neuromuscular do atracúrio e do cisatracúrio. Não alterou o potencial de membrana e ocasionou aumento inicial na freqüência dos PPTM, seguido de bloqueio. CONCLUSÕES: A nifedipina na concentração empregada potencializou o bloqueio neuromuscular produzido pelo atracúrio e cisatracúrio. Estudos eletrofisiológicos demonstraram ação pré-sináptica e ausência de ação despolarizante sobre a fibra muscular.

Palavras-chave

ANIMAIS, BLOQUEADORES DE CANAIS DE CÁLCIO, BLOQUEADORES NEUROMUSCULARES, Não-despolarizantes

Abstract

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 µg.mL-1); atracurium (20 µg.mL-1); cistracurium (3 µg.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.

Keywords

ANIMALS, CALCIUM CHANNEL BLOCKERS, NEUROMUSCULAR BLOCKERS, Nondepolarizing

References

Bikhazi GB, Flores C, Foldes FF. The effect of verapamil and EGTA on the rat phrenic nerve hemidiaphragm preparation. Anesth Analg. 1985;64:505-508.

Salvador A, del Pozo E, Carlos R. Differential effects of calcium channel blocking agents on pancuronium and suxamethonium-induced neuromuscular blockade. Br J Anaesth. 1988;60:495-499.

Kraynack BJ, Lawson NW, Gintautas J. Neuromuscular blocking action of verapamil in cats. Can Anaesth Soc J. 1983;30:242-247.

Kraynack BJ, Lawson NW, Gintautas J. Effects of verapamil on indirect muscle twitch responses. Anesth Analg. 1983;62:827-830.

Del Pozo E, Baeyens JM. Effects of calcium channel blockers on neuromuscular blockade induced by aminoglycoside antibiotics. Eur J Pharmacol. 1986;128:49-54.

Bondi AY. Effects of verapamil on excitation-contraction coupling in frog sartorius muscle. J Pharmacol Exp Ther. 1978;205:49-57.

Sato T, Ono H. Demonstration of slow channel activation in skeletal muscle of the dog. Eur J Pharmacol. 1982;83:177-181.

Anderson KA, Marshall RJ. Interactions between calcium entry blockers and vecuronium bromide in anaesthetized cats. Br J Anaesth. 1985;57:775-781.

Bikhazi GB, Leung I, Flores C. Potentiation of neuromuscular blocking agents by calcium channel blockers in rats. Anesth Analg. 1988;67:1-8.

Durant NN, Nguyen N, Katz RL. Potentiation of neuromuscular blockade by verapamil. Anesthesiology. 1984;60:298-303.

Zalman F, Perloff JK, Durant NN. Acute respiratory failure following intravenous verapamil in Duchenne's muscular dystrophy. Am Heart J. 1983;105:510-511.

Ilias W, Steinbereithner K. Potentiation of pancuronium induced neuromuscular blockade by calcium channel blockers in vitro. J Neural Transm. 1985;64:285-293.

Carpenter RL, Mulroy MF. Edrophonium antagonize combined lidocaine-pacuronium and verapamil- pancuronium neuromuscular blockade in cats. Anesthesiology. 1986;65:506-510.

Lawson NW, Kraynack BJ, Gintautas J. Neuromuscular and electrocardiographic responses to verapamil in dogs. Anesth Analg. 1983;62:50-54.

Reves JG, Kissin I, Lell WA. Calcium entry blockers: uses and implications for anesthesiologists. Anesthesiology. 1982;57:504-518.

Bulbring E. Observation on the isolated phrenic nerve-diaphragm preparation of the rat. Br J Pharmacol. 1946;1:38-61.

Sekerci S, Tulunay M. Interactions of calcium channel blockers with non-depolarising muscle relaxants in vitro. Anaesthesia. 1996;51:140-144.

Wali FA. Interaction of verapamil with d-tubocurarine and cholinergic agonists at the avian neuromuscular junction. Acta Anaesthesiol Scand. 1987;31:15-20.

Wali FA. Verapamil intensifies neuromuscular blockade produced by gallamine and pancuroniumat the chick neuromuscular junction. Pharmacol Res Commun. 1986;18:529-541.

Wali FA. Interaction of verapamil with gallamine and pancuronium and reversal of combined neuromuscular blockade with neostigmine and edrophonium. Eur J Anaesthesiol. 1986;3:385-393.

Jones RM, Cashman JN, Casson WR. Verapamil potentiation of neuromuscular blockade: failure of reversal with neostigmine but prompt reversal with edrophonium. Anesth Analg. 1985;64:1021-1025.

van Poorten JF, Dhasmana KM, Kuypers RS. Verapamil and reversal of vecuronium neuromuscular blockade. Anesth Analg. 1984;63:155-157.

Nayler WG. Tissue-selectivity. Calcium antagonists. 1989:113-129.

Ribeiro JA, Dominguez ML, Goncalves MJ. Purine effects at the neuromuscular junction and their modification by theophylline, imidazole and verapamil. Arch Int Pharmacodyn Ther. 1979;38:206-219.

Standaert FG, Dretchen KL. Cyclic nucleotides in neuromuscular transmission. Anesth Analg. 1981;60:91-99.

Singh BN, Ellrodt G, Peter CT. Verapamil: a review of its pharmacological properties and therapeutic use. Drugs. 1978;15:169-97.

Esau SA. Interaction of theophylline, verapamil, and diltiazem on hamster diaphragm muscle force in vitro. Am J Physiol. 1988;254:C365-C371.

Donaldson PL, Beam KG. Calcium currents in a fast-twitch skeletal muscle of the rat. J Gen Physiol. 1983;82:449-468.

Walsh KB, Bryant SH, Schwartz A. Effect of calcium antagonist drugs on calcium currents in mammalian skeletal muscle fibers. J Pharmacol Exp Ther. 1986;236:403-407.

Chiarandini DJ, Bentley PJ. The effects of verapamil on metabolism and contractility of the toad skeletal muscle. J Pharmacol Exp Ther. 1973;186:52-59.

5dd434320e88258247c63493 rba Articles
Links & Downloads
2352-2291 (Electronic) 0104-0014 (Printed)
Braz J Anesthesiol ©2024 All rights reserved.

Braz J Anesthesiol

Share this page
Page Sections