Background

Sympathetic activation in ischemic heart disease can cause lethal arrhythmias. These often are preceded by premature ventricular complexes (PVCs), which at the cellular level could result from delayed afterdepolarizations.

Objective

The purpose of this study was to identify and map vulnerable areas for arrhythmia initiation after myocardial infarction (MI) and to explore the link between PVCs and cellular events.

Methods

Anterior–septal wall MI was induced by 120 minutes of coronary occlusion followed by reperfusion (27 MI and 16 sham pigs). After 4 weeks, EnSite™ electroanatomic mapping combined with imaging was performed to precisely locate PVC sites of origin and subsequently record monophasic action potentials. Cardiomyocytes were isolated from different regions to study regional cellular remodeling. Isoproterenol was used as a surrogate for adrenergic stimulation both in vivo and in cardiomyocytes.

Results

PVCs originated from the MI border zone (BZ) and occurred at discrete areas with clusters of PVCs within the BZ. At these sites, frequent delayed afterdepolarizations and occasional associated spontaneous action potentials translating to a PVC were present. Cardiomyocytes isolated from the MI BZ exhibited more spontaneous action potentials than cardiomyocytes from remote regions. Sensitivity to adrenergic stimulation was increased in MI, in vivo and in cardiomyocytes. In awake, freely moving MI animals, frequent PVCs, ventricular arrhythmia, and sudden cardiac death occurred spontaneously at moderately elevated heart rates.

Conclusion

Post-MI, arrhythmias initiate from discrete vulnerable areas within the BZ, where delayed afterdepolarizations, related to increased adrenergic response of BZ cardiomyocytes, can generate PVCs.

中文翻译：

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频繁的室性早搏的离散位点聚集在梗死边界区内，与肾上腺素能刺激下的高频率延迟后除极一致

背景

缺血性心脏病中的交感神经激活可导致致命的心律失常。这些通常先于室性早搏 (PVC)，这在细胞水平上可能是由延迟的后除极引起的。

客观的

本研究的目的是识别和绘制心肌梗死 (MI) 后心律失常启动的易损区域，并探索 PVC 与细胞事件之间的联系。

方法

前间隔壁心肌梗死是由 120 分钟的冠状动脉闭塞然后再灌注（27 只心肌梗死和 16 只假猪）诱发的。4 周后，EnSite™ 电解剖标测与成像相结合，以精确定位 PVC 起源部位并随后记录单相动作电位。从不同区域分离心肌细胞以研究区域细胞重塑。异丙肾上腺素被用作体内和心肌细胞中肾上腺素能刺激的替代物。

结果

PVC 起源于 MI 边界区 (BZ)，发生在 BZ 内具有 PVC 集群的离散区域。在这些部位，存在频繁的延迟后去极化和偶尔相关的自发动作电位转化为 PVC。从 MI BZ 分离的心肌细胞比来自偏远地区的心肌细胞表现出更多的自发动作电位。MI、体内和心肌细胞对肾上腺素能刺激的敏感性增加。在清醒、自由活动的 MI 动物中，频繁的 PVC、室性心律失常和心源性猝死在心率适度升高时自发发生。

结论

MI 后，心律失常从 BZ 内的离散易损区域开始，其中延迟的后去极化与 BZ 心肌细胞的肾上腺素能反应增加有关，可产生 PVC。