Hemodynamic effects of teratogenic agents on cardiovasculat function during early developmental stage of morphogenesis

致畸剂对形态发生早期发育阶段心血管功能的血流动力学影响

基本信息

批准号：
61570474
负责人：
NAKAZAWA Makoto
金额：
$ 1.34万
依托单位：
Tokyo Women's Mecical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

Hemodynamic alteration during early stage of development id known to influence cardiovascular morphogenesis. We have investigated the effect of cardioactive agents, whish has also known to be teratogenic in the chick, on the catdiovascular function in the stage 21 check embryo. It was found that isoproterenol and carreine brought about the hemodynamic alteration, which could be positively related to the abnormal morphogenesis of these agents. The eddect of acetylcholine, however, was not found to have a major role in its cardiovascular teratogenesis. We developed a new method to measure the blood pressure and flow parameter(which would estimate cardiac output) in the rat embrto, and obtained"normal" data at 11 to 15 days of gestation. It is reported that caffeine induces different type of cardiovascular anomalies between rat and chick embryos. The effects of caffeine in the rat embryo was different from those in chick embryo, suggesting that the different hemodynamic alteration has a significant role in their different morphogenesis. Bisdiamine is a cardivacular teratogene, which is considered to act by interfering with normal neural crest cell migration. It is reported that neural crest cell ablation affects vagel development. Thus we investigated the effect of bisdiamine, given to pregnant rats, on the hemodynamics of their embryo, and the effect of acetylcholine challenge. The hemodynamic parameters before the challenge were similar between the bisdiamine treated group and the control group. The response of heart rate to acetylcholine was less in the treated ewmbryo, suggesting that bidsiamine might have some direct effect on normal neural crest cell development in the rat model. We conclude that cardioactive agents may be classified into two groups according to the relationship between their hemodynamic effect and teratogenecity ; one brings about its teratogenecity through hemodynamic effect and another does it not by hemodynamic effect.

发育ID的早期阶段的血流动力学改变已知会影响心血管形态发生。我们已经调查了心活性剂的作用，Whish也已知在雏鸡中是致病性的，对21阶段检查胚胎中的Catdievascular功能。已经发现异丙肾上腺素和颈椎引起了血液动力学的改变，这可能与这些药物的异常形态发生呈正相关。然而，未发现乙酰胆碱的涡流在其心血管致畸作用中具有重要作用。我们开发了一种新方法来测量大鼠拥抱中的血压和流量参数（将估计心输出量），并在妊娠11至15天后获得“正常”数据。据报道，咖啡因诱导大鼠和雏鸡胚胎之间的不同类型的心血管异常。咖啡因在大鼠胚胎中的作用与雏鸡胚胎中的作用不同，这表明不同的血液动力学改变在其不同的形态发生中具有重要作用。双歧胺是一种心肌畸胎期，被认为通过干扰正常的神经rest细胞迁移来起作用。据报道，神经rest细胞消融会影响瓦格尔的发育。因此，我们研究了对怀孕大鼠，对胚胎的血液动力学的作用以及乙酰胆碱挑战的作用。在双明治疗组和对照组之间，挑战之前的血液动力学参数相似。在经过治疗的eWmbryo中，心率对乙酰胆碱的反应较少，这表明双胺可能对大鼠模型中正常的神经rest细胞发育有直接影响。我们得出的结论是，根据其血液动力学作用与伤亡性的关系，可以将心活性剂分为两组。一个人通过血流动力学效应带来了其致病性，而另一种不是通过血流动力学作用。