The Effect of Pefloxacin on Rocuronium-Induced Neuromuscular Blockade in Rat Phrenic Nerve-Hemidiaphragm Preparations

Lee, Soo il; Lee, Jong Hwan; Shin, Hoon sik

Abstract

BACKGROUND: At the neuromuscular junction, pefloxacin (P) may exacerbate myasthenia gravis and reduce the tau of MEPC. So here we investigated the effect of P on the neuromuscular blocking action of rocuronium (R).
METHODS
Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). Preparations were bathed in Kreb's solution (in (mM): NaCl 118, KCl 5, CaCl2 2.5, NaHCO3 30, KH2PO4 1, MgCl2 1 and glucose 11), maintained at 32oC and then aerated with a mixture of 95% O2 and 5% CO2. Isometric forces generated in response to 0.1 Hz, and, 50 Hz for 19 seconds with supramaximal electrical stimulation(0.2 msec, rectangular) to the phrenic nerve, were measured with a force transducer. Single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % reduction versus the control, and tetanic fade (TF), as a % increase. Each preparation was exposed to one of 4 P concentrations of Krebs' solution (0, 0.25, 0.5, 1.0 mM), and enough R solution was added to the tissue bath to achieve the desired R concentration. The effects of P and R were allowed to stabilize before measuring tension parameters. EC5, EC25, EC50, EC75, and EC95 of R for ST, PTT and TF were calculated using a probit model. The interactions between the two drugs were drawn with Berenbaum's additive isobole at 25% isobole, 50% isobole, and 75% isobole. Differences between EC50's of R according to P concentrations were tested by one way ANOVA with Tamhane for post hoc; P <0.05 was regarded as significant.
RESULTS
The cumulative concentration-effect curves shifted to the right in ST, and to the left in TF as the concentration of P was increased. The interactions between these two drugs varied from additive to antagonistic according to the magnitude of relaxation effect, drug concentration, and the frequency of stimulation.
CONCLUSIONS
P augmented the TF of R. Our results suggest that simultaneous 0.1 Hz and 50 Hz stimulations allow the neuromuscular blocking action of a drug to be correctly evaluated.