Heterogeneous repolarization creates ventricular tachycardia circuits in healed myocardial infarction scar.
Heterogeneous repolarization creates ventricular tachycardia circuits in healed myocardial infarction scar.
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DOI：
10.1038/s41467-022-28418-1
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发表时间：
2022-02-11
影响因子：
16.6
通讯作者：
Donahue JK
中科院分区：
文献类型：
--
作者：
Kelemen K;Greener ID;Wan X;Parajuli S;Donahue JK
起源于瘢痕心室心肌的心律失常是死亡的主要原因，但允许这些节律存在的潜在机制尚不清楚。这种知识差距严重限制了识别高危患者和治疗一旦心律失常变得明显。在这里，我们发现钾电压门控通道亚家族E调节亚基3和4 （KCNE3, KCNE4）在瘢痕心肌的心律失常部位是唯一上调的。室性心律失常发生在具有独特心肌细胞复极模式的区域，复极时间短的心肌细胞束与复极时间长的心肌细胞束相连。我们只在室性心律失常回路中发现了这种独特的复极化异质性模式。相反，瘢痕内普遍存在传导异常。这些复极化非均质性与KCNE3和KCNE4对慢延迟整流钾电流的功能效应一致。我们使用传统的心脏电生理技术观察到复极化异质性，这可能会转化为识别高危患者。复极化异质性的中和可能是消除室性心律失常回路的一种潜在策略。心脏病发作后的室性心律失常是导致死亡的主要原因。作者在猪模型中表明，KCNE3和KCNE4上调以及疤痕中独特的复极化异质性模式促进了再入性室性心动过速。
Arrhythmias originating in scarred ventricular myocardium are a major cause of death, but the underlying mechanism allowing these rhythms to exist remains unknown. This gap in knowledge critically limits identification of at-risk patients and treatment once arrhythmias become manifest. Here we show that potassium voltage-gated channel subfamily E regulatory subunits 3 and 4 (KCNE3, KCNE4) are uniquely upregulated at arrhythmia sites within scarred myocardium. Ventricular arrhythmias occur in areas with a distinctive cardiomyocyte repolarization pattern, where myocyte tracts with short repolarization times connect to myocytes tracts with long repolarization times. We found this unique pattern of repolarization heterogeneity only in ventricular arrhythmia circuits. In contrast, conduction abnormalities were ubiquitous within scar. These repolarization heterogeneities are consistent with known functional effects of KCNE3 and KCNE4 on the slow delayed-rectifier potassium current. We observed repolarization heterogeneity using conventional cardiac electrophysiologic techniques that could potentially translate to identification of at-risk patients. The neutralization of the repolarization heterogeneities could represent a potential strategy for the elimination of ventricular arrhythmia circuits. Ventricular arrhythmias after heart attack are a leading cause of death. Here the authors show, in a porcine model, that KCNE3 and KCNE4 upregulation and a unique pattern of repolarization heterogeneity in the scar facilitate reentrant ventricular tachycardia.
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影响因子：
37.8
作者：
Igarashi T;Finet JE;Takeuchi A;Fujino Y;Strom M;Greener ID;Rosenbaum DS;Donahue JK
通讯作者：
Donahue JK
DOI：
10.1073/pnas.1718211115
发表时间：
2018-03-27
影响因子：
11.1
作者：
Hegyi, Bence;Bossuyt, Julie;Chen-Izu, Ye
通讯作者：
Chen-Izu, Ye
影响因子：
37.8
作者：
Myerburg, Robert J.;Junttila, M. Juhani
通讯作者：
Junttila, M. Juhani
影响因子：
10.8
作者：
Bendahhou, S;Marionneau, C;Barhanin, J
通讯作者：
Barhanin, J
影响因子：
4.8
作者：
Anantharam, A;Lewis, A;Abbott, GW
通讯作者：
Abbott, GW