An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics.
An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics.
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DOI：
10.1213/ane.0000000000003757
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发表时间：
2020-01
影响因子：
5.7
通讯作者：
Bertaccini EJ
中科院分区：
文献类型：
--
作者：
Chang ACY;Chang ACH;Nicin L;Weber GJ;Holbrook C;Davies MF;Blau HM;Bertaccini EJ
由于缺乏复杂的临床模型，麻醉剂对心脏副作用的了解一直受到阻碍。使用微模式化的人诱导多能干细胞来源的心肌细胞(HiPSC-CMS)，我们获得了异丙酚、依托咪酯和我们新鉴定的麻醉剂化合物KSEB01-S2的心肌抑制药图谱。在所测试的三种化合物中，异丙酚是最强的降压剂，表现出最大的收缩速度、抑制率和搏动频率的下降。有趣的是，KSEB01-S2的作用类似于依托咪酯，表明心脏安全状况更好。我们的结果为将hiPSC-CMS用作未来药物设计的体外平台提供了概念上的证明。
The understanding of anesthetic side-effects on the heart have been hindered by the lack of sophisticated clinical models. Using micropatterned human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs), we obtained cardiac musle depressant profiles for propofol, etomidate, and our newly identified anesthetic compound KSEB01-S2. Propofol was the strongest depressant among the three 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 hiPSC-CMs as an in vitro platform for future drug design.