延迟整流钾通道阻断药物与维拉帕米联合应用对豚鼠心室乳头肌动作电位的影响

目的:研究IKs特异性阻断剂Chromanol 293B、IKr特异性阻断剂多非利特与L-型钙通道阻断剂维拉帕米联合应用对豚鼠心室乳头肌动作电位的作用,探讨Ⅲ类和Ⅳ类抗心律失常药物相互作用的机制。方法:用标准玻璃微电极技术记录豚鼠乳头肌的动作电位,观察不同刺激频率(0.2,0.5,1,1.25,2 Hz)对动作电位各参数的影响。结果:(1)Chromanol 293B(1,5,10μmol.L-1)能剂量依赖性的延长APD,在不同刺激频率下,Chromanol 293B 10μmol.L-1延长APD不具有频率依赖性;(2)Chromanol293B 10μmol.L-1能延长APD90,当加入多非利特0.1μmol.L-1后,显著延长APD90,增强了在低频率时的作用,表现为负性频率依赖性。(3)在结果(2)的基础上加入维拉帕米(0.1、1、2.5μmol.L-1),使APD90有一定程度的缩短,减弱了慢心率时APD90的延长作用。结论:Chromanol 293B是选择性作用于IKs的Ⅲ类抗心律失常药物,非频率依赖性的延长APD:Chromanol 293B与多非利特联合应用明显增强了延长APD的作用,表现为明显的负性频率依赖性。钙通道阻断剂维拉帕米改善了Ⅲ类抗心律失常药物的作用特性,钾和钙通道阻断剂的联合应用减弱了纯Ⅲ类抗心律失常药物导致的负性作用。

Effects of combined use selective blockers of the delayed rectifier potassium current and verapamil on the action potential of papillary muscle in guinea pigs

Objective： To investigate the effect of selective IKs-blocking drug Chromanol 293B and specific IKr-blocking drug dofetilide combined with verapamil on the action potential of papillary muscles in guinea pigs and analyze the interactional mechanism between Class Ⅲ and Ⅳ antiarrhythmic drugs.Methods： The conventional glass microelectrode technique was used to record the action potential of papillary muscle in guinea pigs.The action potential profile was recorded under different stimulation frequencies（0.2,0.5,1.0,1.25,2Hz）.Results： Chromanol 293B（1,5,10μmol·L^-1 lengthen action potential duration APD（APD50,APD90） in a dose-dependent manner（n=6,1Hz）,prolonged APD in independent of stimulation frequency（n=6）;when treated with dofetilide（0.1μmol·L^-1in the presence of Chromanol 293B（10μmol·L^-1,it shows a significant prolonged APD in reversed rate-dependent effect;under the treated with 293B（10μmol·L^-1 and dofetilide（0.1μmol·L^-1,verapamil dose-dependently（0.1,1,2.5,5μmol·L^-1 abbreviated APD.Conclusion： Chromanol 293B is selective IKs blocking agent in independent of stimulation frequency.Combined use Chromanol 293B and dofetilide induced a significant prolonged APD in reversed rate-dependent effects.L-type calcium channel blocking agent verapamil improves the Class Ⅲ antiarrhythmic profile.Potassium and calcium antagonistic activities may exhibit less adverse effects than purely selective Class Ⅲ antiarrhythmic agents.