氟哌啶醇对钾异常时兔浦肯野细胞动作电位的影响

Effects of haloperidol on action potentials of rabbit cardiac Purkinje fibers under abnormal potassium concentrations

目的:观察氟哌啶醇对胞外钾离子浓度异常状态下兔浦肯野纤维细胞动作电位的影响。方法:采用标准微电极技术,观察不同浓度氟哌啶醇对高钾台氏液及低钾台氏液灌流的离体兔浦肯野纤维标本动作电位各电生理参数0期去极化幅值(APA)、最大除极速率(Vmax)、90%动作电位时程(APD90)及有效不应期(ERP)的影响。结果:(1)不同浓度氟哌啶醇对高钾台氏液([K+]=5.4 mmol/L)灌流的心肌传导纤维的APA呈进行性缩短趋势;ERP值较正常值也有缩短,但趋势不明显,至10μmol/L时方有统计学差异;APD90变化相对复杂,0.1、0.3μmol/L两个浓度时较正常值(P<0.05),此后,表现为轻微上升趋势,但仍低于给药前;Vmax值随浓度的增加呈明显浓度依赖性缩短趋势。(2)不同浓度的氟哌啶醇对低钾([K+]=3 mmol/L)台氏液灌流的心肌传导纤维的APA呈先增大后减小的趋势,0.1、0.3、1μmol/L时的APA较给药前略有增大,从3μmol/L时开始减小;ERP的增长较明显,Vmax值呈浓度依赖性缩短,APD90随浓度增大而延长。结论:在使用氟哌啶醇时应密切监测患者血钾浓度,氟哌啶醇可能加重低血钾时APD延长的程度,增加Q-T间期过度延长诱发Tdp的风险。

Objective： To observe the effects of haloperidol on action potentials in rabbit cardiac Purkinje fibers exposed to abnormal extracellular potassium concentrations. Methods： By standard microelectrode technique, we observe the effects of different concentrations of haloperidol （0.1, 0.3, 1,3, 10 μmol/L）on action potential parameters （APA, Vmax, APD90 and ERP） of rabbit cardiac Purkinje fibers which perfused with high K^＋ Tyrode solutions and low K^＋ Tyrode solutions. Results： （1） A progressive shortening of APA was observed in cardiac conductive tissues followed by perfusion of haloperidol with high K^＋ Tyrode solutions. ERP was also shortened compared with normal range but not prominent until the concentration reached to 10μmol/L. Comparatively the changes in APD90 were much more complex. Both haloperidol at 0.1 and 0.3 μmol/L shortened APDg0 significantly compared with normal range and then showed a slight increase but APD90 was still lower before the treatment. Vmax was shortened concentration dependently. （2） In cardiac conductive tissues perfused with low K^＋ Tyrode solutions, different concentrations of haloperidol first increased APA then decreased. When haloperidol were 0.1, 0.3, 1 μmol/L, APA was slightly higher than before treatment and started decreased at 3 μmol/L. ERP was increased significantly and Vmax was shortened in a concentration-dependent manner. APD90 was also increased in a concentfation-dependent manner. Conclusion： A careful monitoring of potassium levels is needed when using haloperidolbecause it might exacerbate APD prolongation induced hypokalemia and increases the risk of Torsades de points （Tdp） induced by Q-T interval excess prolongation.