Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?
Ethanol exposure alters early cardiac function in the looping heart: a mechanism for congenital heart defects?
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DOI：
10.1152/ajpheart.00600.2013
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发表时间：
2014-02-01
影响因子：
4.8
通讯作者：
Watanabe, Michiko
中科院分区：
文献类型：
--
作者：
Karunamuni, Ganga;Gu, Shi;Watanabe, Michiko
酒精引起的先天性心脏病通常是最危及生命的疾病之一，需要对新生儿进行手术矫正。这些缺陷的病因，统称为胎儿酒精综合征，一直是许多研究的重点，特别是涉及细胞和分子机制。由于缺乏能够分析微小跳动心脏的工具，很少有研究讨论心脏功能改变在早期胚胎发生中的影响作用。为了克服我们理解中的这一差距，我们使用光学相干断层扫描（OCT），一种能够进行微米级分辨率成像的无损成像方式，在生理条件下真实的时间内快速准确地绘制心血管结构和血流动力学。在这项研究中，我们暴露于一个单一剂量的酒精/乙醇的禽胚胎原肠胚时，胚胎是敏感的诱导出生缺陷。使用标准组织学分析分析晚期心脏，重点是房室瓣。使用多普勒OCT检测早期心脏功能，并使用OCT成像进行心脏垫的结构分析。我们的结果表明，暴露于乙醇的胚胎出现晚期瓣膜间隔缺损。在早期阶段，与对照组（未注射和注射盐水的胚胎）相比，它们表现出增加的反流和较小的房室心脏垫。胚胎还表现出身体的异常屈曲/扭转。我们的证据表明，乙醇诱导的早期心脏功能改变有可能导致晚期瓣膜和间隔缺损，从而表明功能参数可以作为心脏正常和异常的早期和敏感的衡量标准。
Alcohol-induced congenital heart defects are frequently among the most life threatening and require surgical correction in newborns. The etiology of these defects, collectively known as fetal alcohol syndrome, has been the focus of much study, particularly involving cellular and molecular mechanisms. Few studies have addressed the influential role of altered cardiac function in early embryogenesis because of a lack of tools with the capability to assay tiny beating hearts. To overcome this gap in our understanding, we used optical coherence tomography (OCT), a nondestructive imaging modality capable of micrometer-scale resolution imaging, to rapidly and accurately map cardiovascular structure and hemodynamics in real time under physiological conditions. In this study, we exposed avian embryos to a single dose of alcohol/ethanol at gastrulation when the embryo is sensitive to the induction of birth defects. Late-stage hearts were analyzed using standard histological analysis with a focus on the atrio-ventricular valves. Early cardiac function was assayed using Doppler OCT, and structural analysis of the cardiac cushions was performed using OCT imaging. Our results indicated that ethanol-exposed embryos developed late-stage valvuloseptal defects. At early stages, they exhibited increased regurgitant flow and developed smaller atrio-ventricular cardiac cushions, compared with controls (uninjected and saline-injected embryos). The embryos also exhibited abnormal flexion/torsion of the body. Our evidence suggests that ethanol-induced alterations in early cardiac function have the potential to contribute to late-stage valve and septal defects, thus demonstrating that functional parameters may serve as early and sensitive gauges of cardiac normalcy and abnormalities.