Effects of Nimodipine on Dose-Response Curves of Vecuronium, Rocuronium, and Atracurium Using Phrenic Nerve-Diaphragm Preparations of Rats

Cho, In Hea; Kim, Yun Jin; Baik, Hee Jung; Kim, Jong Hak

Abstract

BACKGROUND: Interactions between nimodipine, a calcium channel blocker, used perioperatively for the treatment of subarachnoid hemorrhage, and vecuronium, rocuronium, and atracurium were studied with phrenic nerve-hemidiaphragm preparations of rats.
METHODS
Male 200-300 g Sprague-Dawley rats were randomly allocated into four groups (control, NMD(5), NMD(50) and NMD(500) group, n = 10, respectively) according to the nimodipine concentration, and three groups (control, NMD(2D) and NMD(7D), n = 10, respectively) according to the pretreatment duration. A square wave 0.1 Hz supramaximal stimuli was applied to the phrenic nerve-hemidiaphragm preparation and the twitch height response was recorded with mechanomyography. The dose-response curves were measured, and ED(5), ED(50), ED(90), and ED(95) of each vecuronium, rocuronium, and atracurium in different concentrations of nimodipine of 5, 50, and 500 ng/ml and rocuronium in pretreatment with nimodipine 2.5 mg/kg/d for 2 and 7 days were calculated using an inhibitory sigmoid Emax model.
RESULTS
The dose-response curves of rocuronium and atracurium were significantly shifted to the left in NMD(500) group, and significantly shifted to the right in NMD(7D) group (P < 0.05). In NMD(500) group, ED(50), ED(90), and ED(95) of rocuronium and atracurium were significantly reduced, and those of rocuronium in NMD7D group were significantly increased compared with the control group (P < 0.05).
CONCLUSIONS
Nimodipine 500 ng/ml in the phrenic nerve-hemidiaphragm preparation of rat increased sensitivity to rocuronium and atracurium, and the dose-response curve was significantly shifted to the left, but following pretreatment for 7 days, nimodipine decreased the potency of rocuronium, and the dose-response curve was significantly shifted to the right.