The effects of verapamil and nimodipine on bupivacaine-induced cardiotoxicity in rats: an in vivo and in vitro study.

Abstract

The purpose of this in vivo and in vitro study was to compare the effects of verapamil or nimodipine pretreatment on bupivacaine-induced cardiotoxicity. In the in vivo study, the dose-response curve for the 50% lethal dose (LD50) of bupivacaine was determined for rats. Two separate groups of rats were pretreated with i.v. verapamil 150 microg/kg (n = 35) or i.v. nimodipine 200 microg/kg (n = 35). Each pretreatment group was then subdivided into four groups of at least four rats each. Three minutes after pretreatment, bupivacaine was administered to each of four groups in doses of 2.5, 3.0, 3.25, and 3.5 mg/kg, respectively. Both verapamil and nimodipine pretreatment increased the LD50 and 95% confidence intervals for bupivacaine and increased survival. In the in vitro study, the effects of verapamil or nimodipine perfusion on bupivacaine cardiotoxicity (negative chronotropic, negative inotropic, and arrhythmogenic effects) and coronary perfusion pressure (CPP) were investigated in isolated, perfused rat heart preparations. Depression of heart rate, contractile force, and CPP, and the incidence of arrhythmias caused by bupivacaine alone were similar to those caused by bupivacaine after verapamil pretreatment. In contrast, bupivacaine induced less negative chronotropic effects (P < 0.05, paired t-test) and arrhythmias (P < 0.05, chi2 analysis) after nimodipine pretreatment. The results of this study demonstrate that both verapamil and nimodipine pretreatment decrease bupivacaine-induced cardiotoxicity in vivo, whereas only nimodipine pretreatment decreased bupivacaine-induced cardiotoxicity and arrhythmias in vitro. In this experimental study consisting of two stages (in vivo and in vitro), we compared the effects of two calcium channel-blocking drugs (verapamil and nimodipine) on bupivacaine toxicity. Bupivacaine is a local anesthetic frequently used in clinical practice, and cardiotoxicity is one of its severe side effects. Verapamil and nimodipine were both effective in decreasing bupivacaine cardiotoxicity in this rat model.