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

在发育早期的血流动力学改变是已知的影响心血管形态发生。我们研究了心脏活性药物对21期检查胚胎心血管功能的影响，这种药物在鸡中也已知是致畸的。发现异丙肾上腺素和卡林引起血流动力学改变，这可能与这些药物的异常形态发生呈正相关。然而，乙酰胆碱的作用并没有被发现在其心血管致畸中起主要作用。我们开发了一种新的方法来测量大鼠胚胎中的血压和血流参数（可以估计心输出量），并获得了妊娠11至15天的“正常”数据。据报道，咖啡因在大鼠和鸡胚胎之间诱导不同类型的心血管异常。咖啡因对大鼠胚胎和鸡胚胎的影响不同，表明不同的血流动力学改变在它们不同的形态发生中起着重要作用。比二胺是一种心血管性致畸物，被认为是通过干扰正常的神经嵴细胞迁移而起作用。据报道，神经嵴细胞消融影响迷走神经的发育。因此，我们研究了双二胺对妊娠大鼠胚胎血流动力学的影响，以及乙酰胆碱刺激的影响。双双胺治疗组与对照组激射前血流动力学参数相似。经乙酰胆碱处理的胚胎心率对乙酰胆碱的反应较弱，提示比脲胺可能对大鼠正常神经嵴细胞发育有一定的直接影响。我们认为心脏活性药物可根据其血流动力学作用与致畸性的关系分为两类；一种是通过血流动力学作用产生致畸性，另一种不是通过血流动力学作用产生致畸性。

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.