The Effect of Kanamycin on Rocuronium Neuromuscular Blockade in Rat Hemidiaphragm-phrenic Nerve Preparations

Lee, Soo Il; Lee, Jong Hwan; Lee, Seung Cheol; Kim, Seung Su

Abstract

BACKGROUND: Kanamycin has been shown to block neuromuscular transmission by reducing acetylcholine can release or blocking postsynaptic receptors. This study was undertaken to investigate whether kanamycin can potentiate rocuronium neuromuscular block.
METHODS
Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Kreb's solution of (mM): NaCl 118, KCl 5, CaCl2 2.5, NaHCO3 30, KH2PO4 1, MgCl2 1 and glucose 11 maintained at 32oC and aerated with a mixture of 95% O2 and 5% CO2. Isometric forces generated in response to 0.1 Hz and 50 Hz for 1.9 seconds with supramaximal electrical stimulation (0.2 msec, rectangular) to the phrenic nerve, were measured using a force transducer. The effects of drugs on single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % inhibition of control and tetanic fade (TF), as % increase. Each preparation (n = 20) was exposed to one of 4 kanamycin concentrations (0.0, 1.0, 2.0, 4.0 mM), and an adequate volume of rocuronium solution was cumulatively added to the tissue bath to achieve a 80-90% reduction in ST. An adequate volume of kanamycin solution was cumulatively added to the other 5 preparations to achieve a 80-90% reduction in ST. The effect of kanamycin or rocuronium at each concentration was allowed to reach a steady state before tension parameters were measured. EC5, EC25, EC50, EC75, and EC95 of rocuronium and kanamycin for ST, PTT and TF were calculated using a probit model. Drug interactions were drawn using Berenbaum's additive isobole at 25% isobole, 50% isobole, and 75% isobole. Differences between EC50's of rocuronium at different kanamycin concentrations were tested using one way ANOVA with Tamhane post hoc analysis, P values of < 0.05 were regarded significant.
RESULTS
Kanamycin shifted cumulative concentration-response curves to the right. The interactions of these drugs varied from additive to antagonistic or synergistic according to the magnitude of neuromuscular block, concentration of the drugs and the frequency of the stimulation.
CONCLUSIONS
Kanamycin lowered the effective concentration of rocuronium, but the interaction between rocuronium and kanamycin was variable.