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, NMD5, NMD50 and NMD500 group, n = 10, respectively) according to the nimodipine concentration, and three groups (control, NMD2D and NMD7D, 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 ED5, ED50, ED90, and ED95 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 NMD500 group, and significantly shifted to the right in NMD7D group (P < 0.05). In NMD500 group, ED50, ED90, and ED95 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.