Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/article/doi/10.1590/S0034-70942007000100008
Brazilian Journal of Anesthesiology
Scientific Article

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

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

Thalita Duque Martins; Yolanda Christina S. Loyola; Angélica de Fátima de Assunção Braga

http://dx.doi.org/10.1590/S0034-70942007000100008 Braz J Anesthesiol, vol.57, n1, p.74-82, 2007
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Resumo

JUSTIFICATIVA E OBJETIVOS: A potencialização da procainamida sobre o bloqueio neuromuscular produzido pela d-tubocurarina já está comprovada, porém o mecanismo é controverso. O objetivo do estudo foi avaliar a influência da procainamida no bloqueio neuromuscular produzido pelo rocurônio e investigar os mecanismos desta interação. MÉTODO: Foram utilizados 15 ratos (250 a 300 g) em preparação descrita por Bülbring. Formaram-se os seguintes grupos (n = 5 cada): procainamida - 20 µg.mL-1 (Grupo I); rocurônio - 4 µg.mL-1 (Grupo II) e rocurônio - 4 µg.mL-1 e procainamida - 20 µg.mL-1 (Grupo III). Avaliaram-se: 1) a amplitude das contrações musculares sob estimulação indireta em cada grupo, antes e após a adição dos fármacos; 2) os potenciais de placa terminal em miniatura (PPTM); 3) a eficácia da 4-aminopiridina na reversão do bloqueio neuromuscular. O mecanismo da interação foi estudado em Biventer cervicis (n = 5) e diafragma de rato desnervado (n = 5), observando-se a influência da procainamida na resposta à acetilcolina antes e após a adição da procainamida. RESULTADOS: A procainamida isoladamente não alterou as respostas neuromusculares. O bloqueio produzido com o Grupo III foi de 68,6% ± 7,1%, com diferença significativa (p = 0,0067) em relação ao Grupo II (10,4% ± 4,5%), revertido pela 4-aminopiridina. A procainamida ocasionou aumento na freqüência dos PPTM, seguido de bloqueio revertido pela 4-aminopiridina. Em Biventer cervicis a procainamida aumentou a resposta à ação de contração da acetilcolina, resultado não observado com o diafragma desnervado. CONCLUSÕES: A procainamida potencializou o bloqueio produzido pelo rocurônio. As alterações observadas com PPTM e Biventer cervicis identificaram ação pré-sináptica. O antagonismo da 4-aminopiridina sobre o bloqueio dos PPTM sugeriu dessensibilização dos receptores pela procainamida.

Palavras-chave

ANIMAL, ANTIARRÍTMICOS, BLOQUEADORES NEUROMUSCULARES, Não-despolarizantes, DROGAS

Abstract

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 µg.mL-1 (Group I); rocuronium - 4 µg.mL-1 (Group II); and rocuronium - 4 µg.mL-1 and procainamide - 20 µg.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.

Keywords

ANIMAL, ANTI-ARRHYTHMICS, DRUGS, NEUROMUSCULAR BLOCKERS, Nondepolarizing

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