Nattel S, Elharrar V, Zipes D P, Bailey J C
Circ Res. 1981 Jan;48(1):55-61. doi: 10.1161/01.res.48.1.55.
We used standard microelectrode techniques to evaluate the effects of lidocaine and quinidine on canine Purkinje fibers at normal pH (7.3) and in the presence of acidosis (pH 6.9). Acidosis alone reduced resting potential, action potential amplitude, and Vmax, while increasing APD90 and conduction time. Lidocaine concentrations of 6 x 10(-6) to 1.5 x 10(-5) M had minimal effect on resting potential, action potential amplitude, and Vmax at pH 7.3. At pH 6.9, the same lidocaine concentrations significantly reduced resting potential (3-10%), action potential amplitude (3-8%) and Vmax (14-22%). Quinidine (6 x 10(-6) to 1.5 x 10(-5) M) reduced resting potential (3-5%), action potential amplitude (4-9%), and Vmax (19-34%) at pH 7.3. At pH 6.9, quinidine produced significantly greater reductions in resting potential (4-15%), action potential amplitude (5-18%), and Vmax (22-49%). These changes were associated with much more quinidine- and lidocaine-induced prolongation of interelectrode conduction time at acidic than at normal pH. Inexcitability occurred at pH 6.9 in four of 14 experiments with 1.5 x 10(-5) M quinidine and in two of 10 with 1.5 x 10(-5) M lidocaine, and was reversed at the same drug concentration by normalizing pH. Acidosis did not alter the Vmax-resting potential relationship in either the absence or presence of antiarrhythmic agents. Furthermore, changes in ionization did not account for the alterations in electrophysiological effects of quinidine and lidocaine produced by acidosis. Our data suggest that extracellular pH changes may modify importantly the effects of antiarrhythmic agents.
我们采用标准微电极技术，评估利多卡因和奎尼丁在正常pH值（7.3）及存在酸中毒（pH 6.9）情况下对犬浦肯野纤维的影响。单独的酸中毒会降低静息电位、动作电位幅度和Vmax，同时增加APD90和传导时间。在pH 7.3时，6×10⁻⁶至1.5×10⁻⁵ M的利多卡因浓度对静息电位、动作电位幅度和Vmax影响极小。在pH 6.9时，相同的利多卡因浓度会显著降低静息电位（3% - 10%）、动作电位幅度（3% - 8%）和Vmax（14% - 22%）。在pH 7.3时，奎尼丁（6×10⁻⁶至1.5×10⁻⁵ M）会降低静息电位（3% - 5%）、动作电位幅度（4% - 9%）和Vmax（19% - 34%）。在pH 6.9时，奎尼丁会使静息电位（4% - 15%）、动作电位幅度（5% - 18%）和Vmax（22% - 49%）出现更显著的降低。这些变化与在酸性条件下比在正常pH值时更多的奎尼丁和利多卡因诱导的电极间传导时间延长有关。在14个使用1.5×10⁻⁵ M奎尼丁的实验中有4个、10个使用1.5×10⁻⁵ M利多卡因的实验中有2个在pH 6.9时出现了兴奋性丧失，并且在相同药物浓度下通过将pH值恢复正常而得以逆转。无论是否存在抗心律失常药物，酸中毒均未改变Vmax - 静息电位关系。此外，离子化的变化并不能解释酸中毒所导致的奎尼丁和利多卡因电生理效应的改变。我们的数据表明，细胞外pH值的变化可能会显著改变抗心律失常药物的作用。
