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 to 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, 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.

中文翻译：

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产前乙醇暴露会损害循环心脏房室交界处的传导延迟

乙醇相关先天性心脏缺陷的病因一直是许多研究的焦点，但大多数研究都集中在细胞和分子机制上。我们通过光学相干断层扫描（OCT）显示，与对照组相比，乙醇暴露导致逆行血流增加和房室（AV）垫变小。由于 AV 垫在房室交界处 (AVJ) 的传导延迟模式中发挥作用，因此本研究旨在调查乙醇暴露是否会改变早期循环心脏中的 AVJ 传导，以及这种改变是否与垫尺寸减小有关。鹌鹑胚胎在原肠胚形成时暴露于单剂量乙醇，并解剖汉堡-汉密尔顿阶段 19 - 20 颗心脏进行成像。使用光学映射显微镜测量心脏传导，并使用 OCT 对心内膜垫进行成像。我们的结果表明，与对照组相比，暴露于乙醇的胚胎表现出异常快速的 AVJ 传导和减小的缓冲垫尺寸。然而，传导速度（CV）的增加与垫体积和厚度的减少并不严格相关。通过将 CV 图与衬垫尺寸图进行匹配，我们发现最慢的传导位置始终位于 AVJ 的心房侧，该侧具有较薄的衬垫，而不是如预期的那样位于心室侧最厚的衬垫位置。我们的研究结果揭示了 AVJ 心肌的区域差异，即使在心脏发育的早期阶段也是如此。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，而成熟 AVJ 是引发心律失常的部位。