Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia.
Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia.
复制标题
DOI：
10.1161/01.cir.95.4.988
复制
发表时间：
1997-02
期刊：
影响因子：
37.8
通讯作者：
N. Peters;J. Coromilas;N. Severs;A. L. Wit
中科院分区：
文献类型：
--
作者：
N. Peters;J. Coromilas;N. Severs;A. L. Wit
背景：梗塞相关心肌的缝隙连接偶联异常引起的缓慢、不均匀传导被认为是致心律失常底物的一个组成部分。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Cx43(Cx43)的免疫定位相关联，验证了犬心梗愈合过程中心外膜交界区(EBZ)缝隙连接分布的变化决定了折返性室性心动过速(VT)回路的位置的假设。方法与结果用高分辨率电极阵列对3只VT可诱导性和3只非诱导性VT犬4d龄前脑梗死灶上方的EBZ进行了标测，并用标准组织学和Cx43的免疫共聚焦定位进行了系统研究。室速为(538+/-257微米)的心脏EBZ厚度显著小于无室速(840+/-132微米；P<；0.05)的心脏。在与坏死细胞的交界处，EBZ心肌显示明显的缝隙连接分布中断，Cx43标记的标记沿细胞的外侧表面异常地纵向排列。在所有心脏的EBZ，被破坏的Cx43标记延伸到心外膜表面的一部分，最浅的心外膜肌细胞具有正常的横向定位模式。只有在有诱导性室速的心脏中，在与8字形折返性室速回路的中央共同通路的位置相关的部位，这种紊乱才会延伸到整个存活层的厚度。结论缝隙连接分布改变是心肌梗死后早期重构的一部分，通过确定折返性室速回路共同中心通路的位置，它可能是室速易感性的决定因素。
BACKGROUND 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). METHODS AND RESULTS 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. CONCLUSIONS 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.