普罗帕酮对离体缺血兔心肌心室间复极异质性的影响

Effects of propafenone on interventricular repolarization heterogeneity in ischemic myocardium in rabbits

目的观察普罗帕酮对离体缺血兔心肌心室间复极异质性的影响,探讨普罗帕酮对缺血心肌“致心律失常作用”的电药理学机制。方法采用全细胞膜片钳技术,观察在不同刺激频率(即基础循环周长,BCL=2000、1000、500、250ms)下,不同浓度(1、6、10μmol/L)的普罗帕酮对缺血心肌左右心室心内膜心肌细胞动作电位时程(APD)的影响。结果普罗帕酮由低浓度(1μmol/L)至超治疗浓度(10μmol/L)均增大室间离散;左右心室心内膜心肌细胞APD(n=10)在不同浓度的普罗帕酮干预下仍具有慢频率依赖性特点(P<0.05),且对普罗帕酮呈非浓度依赖性,但室间离散的慢频率依赖性特点消失。结论普罗帕酮可增大缺血心肌左右心室间的复极离散,并使其慢频率依赖性特点消失,这可能是普罗帕酮对缺血心肌“致心律失常作用”的电药理学机制之一。

AIM： To observe the effects of propafenone on interventricular repolarization heterogeneity between two ventricles in isolated ischemic myocardium in rabbits, and with the action potential duration （APD）, to approach the electropharmacologic mechanism of arrhythmogenic of propafenone in patients with myocardium ischemia in clinical practice. METHODS： To observe the effect of propafenone, we gave various concentration gradient （1, 6, 10 μmol/L） on the APD of endocardium myocytes in ischemic state with whole cell patch-clamp through alterring frequency of stimulation. RESULTS： Propafenone could enlarge the interventricular repolarization dispersion when the concentration of propafenone from 1 to 10 μmol/L. The endocardium APD characterized dependence on slow frequency when given various gradients of propafenone （ P 〈 0.05） and this characteristic was independent on the gradients of propafenone. But the slowfrequency dependence of interventricular dispersion was not observed in same condition. CONCLUSION： Propafenone can significantly increase the interventricular repolarization heterogeneity in ischemic myocardium and make the slow-frequency dependence of interventricular dispersion disappear. It may be one of the electropharmacological mechanism of arrhythmogenic of propafenone in ischemic myocardium.