From the *Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California †Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California ‡Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California §Division of Cardiology, University of Washington, Seattle, Washington ‖Department of Anesthesia, Stanford University School of Medicine, Stanford, California ¶Palo Alto Veterans Affairs Health Care System, Palo Alto, California.
Anesth Analg. 2020 Jan;130(1):e1-e4. doi: 10.1213/ANE.0000000000003757.
The understanding of anesthetic side effects on the heart has been hindered by the lack of sophisticated clinical models. Using micropatterned human-induced pluripotent stem cell-derived cardiomyocytes, we obtained cardiac muscle depressant profiles for propofol, etomidate, and our newly identified anesthetic compound KSEB01-S2. Propofol was the strongest depressant among the 3 compounds tested, exhibiting the largest decrease in contraction velocity, depression rate, and beating frequency. Interestingly, KSEB01-S2 behaved similarly to etomidate, suggesting a better cardiac safety profile. Our results provide a proof-of-concept for using human-induced pluripotent stem cell-derived cardiomyocytes as an in vitro platform for future drug design.
麻醉副作用对心脏的影响一直受到缺乏复杂临床模型的阻碍。使用微图案化的人诱导多能干细胞衍生的心肌细胞，我们获得了异丙酚、依托咪酯和我们新鉴定的麻醉化合物 KSEB01-S2 的心肌抑制谱。在测试的 3 种化合物中，异丙酚是最强的抑制剂，表现出收缩速度、抑制率和跳动频率的最大降低。有趣的是，KSEB01-S2 的行为类似于依托咪酯，表明具有更好的心脏安全性。我们的结果为使用人诱导多能干细胞衍生的心肌细胞作为未来药物设计的体外平台提供了概念验证。
