罗哌卡因和布比卡因对豚鼠心室肌细胞L-型钙电流的影响

Effects of ropivacaine and bupivacaine on L-type calcium currents in ventricular cardiomyocytes of guinea

目的观察罗哌卡因和布比卡因对豚鼠心室肌细胞L-型钙电流(ICa-L)的影响,探讨其心肌负性肌力作用的机制。方法以急性酶解法获得豚鼠的单个心室肌细胞,用标准的全细胞膜片钳技术记录ICa-L。结果100/μmol/L的罗哌卡因和布比卡因分别使豚鼠心室肌细胞ICa-L峰值降低(37±3)%和(42±5)%,两者比较差异有统计学意义(P<0.05);两种药物均使电流密度-电压曲线上移,但不改变激活ICa-L的电压和曲线的形态。罗哌卡因和布比卡因均呈浓度依赖性阻滞豚鼠心室肌细胞ICa-L,半最大抑制浓度分别为212±38、(161±20)μmol/L。结论罗哌卡因和布比卡因均呈浓度依赖性阻滞豚鼠心室肌细胞ICa-L,可能是其产生心肌负性肌力作用的主要机制。

Objective To evaluate the effect of ropivacaine and bupivacaine on L-type calcium current (ICa-L) in ventricular myocytes of guinea pigs and to identify the probable mechanism of their negative inotropic effect on myocardium. Methods Single ventricular myocytes were enzymatically isolated from adult male guinea pigs weighing 300-350 g using the enzymatic dissociation method as described by Liu et al. The whole-cell patch clamp technique was used to record ICa-L Results 100 μmol·L-1 ropivacaine and bupivacaine decreased the peak current of ICa-L by 37% ± 3% and 42% ± 5% respectively ( P < 0.05) , but did not alter the threshold potential, the peak potential and the shape of the current density voltage curve of ICa-L . Ropivacaine and bupivacaine inhibited ICa-L in a concentration dependent manner and the half-maximum inhibitory concentration (IC50) was (212 ± 38) μmol·L-1 and (161 ± 20) μmol·L-1 respectively.Conclusion Ropivacaine and bupivacaine decrease ICa-L in ventricular myocytes in concentration-dependent manner and their negative inotropic effect on myocardium may be explained by inhibition of ICa-L.