Revista Brasileira de Anestesiologia
Print version ISSN 0034-7094
MARTINS, Thalita Duque; LOYOLA, Yolanda Christina S. and BRAGA, Angélica de Fátima de Assunção. Influence of procainamide on the neuromuscular blockade caused by rocuronium and investigation on the mechanism of action of procainamide on the neuromuscular junction. Rev. Bras. Anestesiol. [online]. 2007, vol.57, n.1, pp. 74-82. ISSN 0034-7094. http://dx.doi.org/10.1590/S0034-70942007000100008.
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 [rat]; ANTI-ARRHYTHMICS [procainamide]; DRUGS [interaction]; NEUROMUSCULAR BLOCKERS, Nondepolarizing [rocuronium].