Prenatal ethanol exposure impairs the conduction delay at the atrioventricular junction in the looping heart.
Prenatal ethanol exposure impairs the conduction delay at the atrioventricular junction in the looping heart.
复制标题
产前乙醇暴露会损害循环心脏房室交界处的传导延迟。
DOI：
10.1152/ajpheart.00107.2021
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Rollins,AndrewM
中科院分区：
文献类型：
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作者：
Ling,Shan;Jenkins,MichaelW;Watanabe,Michiko;Ford,StephanieM;Rollins,AndrewM
与酒精相关的先天性心脏病的病因一直是许多研究的重点，但大多数研究集中在细胞和分子机制上。我们用光学相干断层扫描(OCT)显示，与对照组相比，酒精暴露导致逆行血流增加，房室(AV)垫变小。由于房室交界处的房室垫在房室交界处的传导延迟形成模式中起作用，因此本研究旨在探讨酒精暴露是否改变了房室交界处早期的房室交界处的传导，以及这种改变是否与房室交界处的气垫尺寸变小有关。在原肠发育时，将鹌鹑胚胎暴露在单剂量的乙醇中，并解剖Hamburger-Hamilton阶段19-20个心脏进行成像。用光学标测显微镜测量心脏传导，用OCT成像心内膜垫。我们的结果表明，与对照组相比，酒精暴露的胚胎表现出异常快的AVJ传导和减小的垫子尺寸。然而，这种传导速度(CV)的增加与坐垫体积和厚度的减少并没有严格的相关性。通过将CV图与流入心管的垫子大小图进行匹配，我们发现最慢的传导位置始终是在房室结的心房侧，那里有较薄的垫层，而不是像预期的那样在室壁的最厚的垫层位置。我们的发现表明，即使在心脏发育的早期阶段，AVJ心肌也存在地区差异。这些发现揭示了导致成熟aVJ传导异质性和复杂性的早期步骤，aVJ是引发心律失常的部位。据我们所知，这是第一项研究酒精暴露对早期心脏传导系统的影响。我们的结果表明，酒精暴露的胚胎表现出异常快速的房室传导。此外，我们在心动过速和心内膜垫厚度的测量中发现，即使在心脏发育的早期阶段，aVJ心肌也存在区域差异，这表明该部位的分化和成熟是复杂的，值得进一步研究。
The etiology of ethanol-related congenital heart defects has been the focus of much study, but most research has concentrated on cellular and molecular mechanisms. We have shown with optical coherence tomography (OCT) that ethanol exposure led to increased retrograde flow and smaller atrioventricular (AV) cushions compared with controls. Since AV cushions play a role in patterning the conduction delay at the atrioventricular junction (AVJ), this study aims to investigate whether ethanol exposure alters the AVJ conduction in early looping hearts and whether this alteration is related to the decreased cushion size. Quail embryos were exposed to a single dose of ethanol at gastrulation, and Hamburger–Hamilton stage 19–20 hearts were dissected for imaging. Cardiac conduction was measured using an optical mapping microscope and we imaged the endocardial cushions using OCT. Our results showed that, compared with controls, ethanol-exposed embryos exhibited abnormally fast AVJ conduction and reduced cushion size. However, this increased conduction velocity (CV) did not strictly correlate with decreased cushion volume and thickness. By matching the CV map to the cushion-size map along the inflow heart tube, we found that the slowest conduction location was consistently at the atrial side of the AVJ, which had the thinner cushions, not at the thickest cushion location at the ventricular side as expected. Our findings reveal regional differences in the AVJ myocardium even at this early stage in heart development. These findings reveal the early steps leading to the heterogeneity and complexity of conduction at the mature AVJ, a site where arrhythmias can be initiated.NEW & NOTEWORTHYTo the best of our knowledge, this is the first study investigating the impact of ethanol exposure on the early cardiac conduction system. Our results showed that ethanol-exposed embryos exhibited abnormally fast atrioventricular conduction. In addition, our findings, in CV measurements and endocardial cushion thickness, reveal regional differences in the AVJ myocardium even at this early stage in heart development, suggesting that the differentiation and maturation at this site are complex and warrant further studies.