晚钠电流及其速率依赖性在急性心肌梗死后心律失常发生机制中的作用

王梁 综述 李晶洁,2 审校

(1.哈尔滨医科大学附属第一医院，黑龙江 哈尔滨 150000； 2.哈尔滨医科大学附属第一医院心内科，黑龙江 哈尔滨 150000)

室性心律失常所致的心源性猝死每年可导致全球4～5百万人的死亡，其中心肌梗死是导致室性心律失常的主要原因之一[1-2]。心律失常起因于动作电位的激动顺序，传播和恢复出现异常，这些步骤是通过电压门控离子通道的打开和关闭来完成的。急性心肌梗死(acute myocardial infarction,AMI)可导致心肌细胞离子电流的功能出现异常，最终导致细胞内钙超载，进而对心肌细胞造成结构性和功能性的损伤[3]。

1 晚钠电流

1.1 晚钠电流的定义及生理功能

1.2 INaL在AMI后的病理学改变

利用细胞膜片钳技术发现，在AMI后心肌的代谢产物、过氧化氢、缺氧可导致INaL幅度明显增加[5-7]，Na+内流显著增加引起的胞内钠超载，能够激活钠钙交换体，继而导致钙内流增加，引发钙超载[8-10]。因此，INaL被广泛认为是钠钾交换(Na+/K+)的核心，同时影响钠钙交换体(Na+/Ca2+exchanger,NCX)及钠氢交换体(Na+/H+exchanger,NHE)，从而影响离子平衡[11-13]。

1.3 INaL在心律失常中的作用

图1 INaL增高促进心律失常的发生机制

图2 INaL与动作电位时程之间的关系

1.4 阻断INaL对AMI后心脏的作用

2 速率依赖性

2.1 速率依赖性及其作用

哺乳动物心室肌复极化(由体表心电图上的QT间期表示)与心率成反比，即心率加快，动作电位时程(action potential duration,APD)/QT间期缩短；心率减慢，APD/QT间期延长[27]。也就是说，心动过速通常会缩短心室复极化并使其延长。这种特性称之为速率依赖性。心室动作电位的持续时间由细胞膜中通道的向内和向外离子电流的动态平衡来确定。理论上，与速率相关的变化离子通道(打开、关闭、灭活)的三种状态中的任何一种可以影响通道的激活、失活和恢复，并且随后转化为APD/QT的变化。

2.2 速率依赖性与INaL之间的关系

3 结语与展望

在急性心肌缺血事件发生时，由于不同部位血管阻塞所致的梗死部位的差异，INaL的增强也相应具有异质性。与此同时，在由AMI导致的不同类型心律失常(缓慢型或快速型)情况下,INaL及其速率依赖性(即在心率加快时，表达减少；在心率减慢时，表达增多)在AMI中的作用具有差异，对临床个体化治疗也提出了更高的要求。因此，在急性心肌缺血事件所致的缓慢型心律失常与快速型心律失常的情况下，抑制INaL是否具有明显差异？是否依然可以促进缺血的心肌获益？这仍是需探讨解决的。

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