晚鈉電流及其速率依賴性在急性心肌梗死后心律失常發(fā)生機(jī)制中的作用

王梁 綜述 李晶潔,2 審校

(1.哈爾濱醫(yī)科大學(xué)附屬第一醫(yī)院，黑龍江 哈爾濱 150000； 2.哈爾濱醫(yī)科大學(xué)附屬第一醫(yī)院心內(nèi)科，黑龍江 哈爾濱 150000)

室性心律失常所致的心源性猝死每年可導(dǎo)致全球4～5百萬(wàn)人的死亡，其中心肌梗死是導(dǎo)致室性心律失常的主要原因之一[1-2]。心律失常起因于動(dòng)作電位的激動(dòng)順序，傳播和恢復(fù)出現(xiàn)異常，這些步驟是通過(guò)電壓門控離子通道的打開(kāi)和關(guān)閉來(lái)完成的。急性心肌梗死(acute myocardial infarction,AMI)可導(dǎo)致心肌細(xì)胞離子電流的功能出現(xiàn)異常，最終導(dǎo)致細(xì)胞內(nèi)鈣超載，進(jìn)而對(duì)心肌細(xì)胞造成結(jié)構(gòu)性和功能性的損傷[3]。

1 晚鈉電流

1.1 晚鈉電流的定義及生理功能

1.2 INaL在AMI后的病理學(xué)改變

利用細(xì)胞膜片鉗技術(shù)發(fā)現(xiàn)，在AMI后心肌的代謝產(chǎn)物、過(guò)氧化氫、缺氧可導(dǎo)致INaL幅度明顯增加[5-7]，Na+內(nèi)流顯著增加引起的胞內(nèi)鈉超載，能夠激活鈉鈣交換體，繼而導(dǎo)致鈣內(nèi)流增加，引發(fā)鈣超載[8-10]。因此，INaL被廣泛認(rèn)為是鈉鉀交換(Na+/K+)的核心，同時(shí)影響鈉鈣交換體(Na+/Ca2+exchanger,NCX)及鈉氫交換體(Na+/H+exchanger,NHE)，從而影響離子平衡[11-13]。

1.3 INaL在心律失常中的作用

圖1 INaL增高促進(jìn)心律失常的發(fā)生機(jī)制

圖2 INaL與動(dòng)作電位時(shí)程之間的關(guān)系

1.4 阻斷INaL對(duì)AMI后心臟的作用

2 速率依賴性

2.1 速率依賴性及其作用

哺乳動(dòng)物心室肌復(fù)極化(由體表心電圖上的QT間期表示)與心率成反比，即心率加快，動(dòng)作電位時(shí)程(action potential duration,APD)/QT間期縮短；心率減慢，APD/QT間期延長(zhǎng)[27]。也就是說(shuō)，心動(dòng)過(guò)速通常會(huì)縮短心室復(fù)極化并使其延長(zhǎng)。這種特性稱之為速率依賴性。心室動(dòng)作電位的持續(xù)時(shí)間由細(xì)胞膜中通道的向內(nèi)和向外離子電流的動(dòng)態(tài)平衡來(lái)確定。理論上，與速率相關(guān)的變化離子通道(打開(kāi)、關(guān)閉、滅活)的三種狀態(tài)中的任何一種可以影響通道的激活、失活和恢復(fù)，并且隨后轉(zhuǎn)化為APD/QT的變化。

2.2 速率依賴性與INaL之間的關(guān)系

3 結(jié)語(yǔ)與展望

在急性心肌缺血事件發(fā)生時(shí)，由于不同部位血管阻塞所致的梗死部位的差異，INaL的增強(qiáng)也相應(yīng)具有異質(zhì)性。與此同時(shí)，在由AMI導(dǎo)致的不同類型心律失常(緩慢型或快速型)情況下,INaL及其速率依賴性(即在心率加快時(shí)，表達(dá)減少；在心率減慢時(shí)，表達(dá)增多)在AMI中的作用具有差異，對(duì)臨床個(gè)體化治療也提出了更高的要求。因此，在急性心肌缺血事件所致的緩慢型心律失常與快速型心律失常的情況下，抑制INaL是否具有明顯差異？是否依然可以促進(jìn)缺血的心肌獲益？這仍是需探討解決的。

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