Readhead Carol, Mahler Simon, Dong Zhenyu, Sato Yuki, Yang Changhuei, Bronner Marianne E
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Department of Electrical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Dev Biol. 2025 Mar;519:46-54. doi: 10.1016/j.ydbio.2024.12.005. Epub 2024 Dec 13.
Using our recently developed laser speckle contrast imaging (LSCI) to visualize blood vessels and monitor blood flow noninvasively, we test the utility of the developing chick heart as a functional model for drug screening. To this end, we examined the effects of antihypertensive agents Nifedipine and Amlodipine, belonging to the L-type calcium channel antagonist family, on blood flow visualized noninvasively through the intact shell. Guided by the live view mode, the drugs were injected through the shell and ventral to HH16-19 chick embryos. Our results show a significant reduction in the chick's heart rate, blood flow, and vascular size within 5-20 min after Nifedipine or Amlodipine injection. For moderate Nifedipine concentrations, these parameters returned to initial values within 2-3 h. Nifedipine showed a rapid reduction in heart rate and blood flow dynamics at a concentration ten times lower than Amlodipine. These findings show that our LSCI system can monitor and distinguish the chick heart's response to injected drugs from the same family. This serves as proof-of-concept, paving the way for a rapid, cost-effective, and quantitative test system for screening drugs that affect the cardiovascular system of live chick embryos. Live noninvasive imaging may also provide insights into the development and functioning of the vertebrate heart.
我们使用最近开发的激光散斑对比成像(LSCI)来可视化血管并无创监测血流,以此测试发育中的鸡胚心脏作为药物筛选功能模型的效用。为此,我们研究了属于L型钙通道拮抗剂家族的降压药硝苯地平和氨氯地平,对通过完整蛋壳无创可视化的血流的影响。在实时观察模式的引导下,将药物通过蛋壳注射到HH16 - 19期鸡胚的腹部。我们的结果显示,注射硝苯地平或氨氯地平后5 - 20分钟内,鸡胚的心率、血流和血管大小显著降低。对于中等浓度的硝苯地平,这些参数在2 - 3小时内恢复到初始值。硝苯地平在浓度比氨氯地平低十倍时,心率和血流动力学就迅速降低。这些发现表明,我们的LSCI系统可以监测并区分鸡胚心脏对同一药物家族注射的反应。这作为概念验证,为快速、经济高效且定量的药物筛选测试系统铺平了道路,该系统用于筛选影响活鸡胚心血管系统的药物。实时无创成像也可能为脊椎动物心脏的发育和功能提供见解。