The Effect of Nicorandil on the Pharmacodynamics of Rocuronium

Abstract

Background: Some investigators have shown that nicorandil, a KATP channel opener, depresses the neuromuscular transmission contraction of the skeletal muscle. However, others have reported that it improves the recovery of vecuronium relaxation and the myotonic activity of muscle. This study investigated the effect of nicorandil on rocuronium relaxation. Methods: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). The preparations were bathed in Krebs' solution containing in (mM): NaCl 118, KCl 5, 2.5, 30, 1, 1 and glucose 11. The preparations were, then maintained at 32 and aerated with a mixture of 95% and 5% . Isometric forces that were 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 single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % inhibition of the control, and the tetanic fade (TF), as % increase in the PTT. Each preparation was exposed to one of the 6 nicorandil concentrations (0.0, 0.625, 1.25, 2.5, 5, 10), and the adequate volume of the rocuronium solution was cumulatively added to the tissue bath for a desired rocuronium concentration until there was an 80-90% decrease in the ST. The effect of rocuronium at each concentration was allowed to reach a steady state before the tension parameters were measured. The , , 0, , and of rocuronium for the ST, PTT and TF were calculated using a probit model. The differences between the 0 of rocuronium according to the nicorandil concentrations were tested using a t-test and a Bonferroni's correction. Results: 1.25 and 2.5 nicorandil shifted the cumulative concentration-response curves for the TF of rocuronium to the right. 5 and 10 nicorandil shifted the cumulative concentration-response curves for the ST of rocuronium to the left. Conclusions: Lower concentration of nicorandil may help maintain the tetanic contraction during rocuronium relaxation