Peters N S, Coromilas J, Severs N J, Wit A L
Department of Cardiology, St Mary's Hospital, London, UK.
Circulation. 1997 Feb 18;95(4):988-96. doi: 10.1161/01.cir.95.4.988.
Slow, nonuniform conduction caused by abnormal gap-junctional coupling of infarct-related myocardium is thought to be a component of the arrhythmogenic substrate. The hypothesis that changes in gap-junctional distribution in the epicardial border zone (EBZ) of healing canine infarcts define the locations of reentrant ventricular tachycardia (VT) circuits was tested by correlating activation maps of the surviving subepicardial myocardial layer with immunolocalization of the principal gap-junctional protein, connexin43 (Cx43).
The EBZ overlying 4-day-old anterior infarcts in three dogs with inducible VT and three noninducible dogs was mapped with a high-resolution electrode array and systematically examined by standard histology and confocal immunolocalization of Cx43. The thickness of the EBZ was significantly less in the hearts with (538 +/- 257 microns) than without (840 +/- 132 microns; P < .05) VT. At the interface with the underlying necrotic cells, the EBZ myocardium showed a marked disruption of gap-junctional distribution, with Cx43 labeling abnormally arrayed longitudinally along the lateral surfaces of the cells. In the EBZ of all hearts, the disrupted Cx43 labeling extended part of the way to the epicardial surface, with the most superficial epicardial myocytes having the normal transversely orientated pattern. Only in the hearts with inducible VT did the disorganization extend through the full thickness of the surviving layer at sites correlating with the location of the central common pathways of the figure-of-8 reentrant VT circuits.
Altered gap-junctional distribution is part of the early remodeling of myocardium after infarction, and by defining the location of the common central pathway of the reentrant VT circuits, it may be a determinant of VT susceptibility.
梗死相关心肌的异常缝隙连接耦联导致的缓慢、不均一传导被认为是致心律失常基质的一个组成部分。通过将存活的心外膜下心肌层的激活图与主要缝隙连接蛋白连接蛋白43（Cx43）的免疫定位相关联，对愈合的犬梗死灶心外膜边界区（EBZ）缝隙连接分布变化确定折返性室性心动过速（VT）环路位置的假说进行了验证。
对3只可诱导VT的犬和3只不可诱导VT的犬，用高分辨率电极阵列对覆盖4日龄前壁梗死灶的EBZ进行标测，并通过标准组织学和Cx43的共聚焦免疫定位进行系统检查。有VT的心脏EBZ厚度（538±257微米）显著小于无VT的心脏（840±132微米；P<.05）。在与下层坏死细胞的界面处，EBZ心肌显示缝隙连接分布明显破坏，Cx43标记沿细胞侧面纵向异常排列。在所有心脏的EBZ中，Cx43标记破坏部分延伸至心外膜表面，最表层的心外膜心肌细胞具有正常的横向排列模式。仅在可诱导VT的心脏中，紊乱在与8字形折返VT环路中央共同通路位置相关的部位贯穿存活层的全层。
缝隙连接分布改变是梗死后心肌早期重塑的一部分，通过确定折返VT环路中央共同通路的位置，它可能是VT易感性的一个决定因素。
