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Anesth Analg. 2018 Sep 5. doi: 10.1213/ANE.0000000000003757. [Epub ahead of print]

An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics.

Author information

1
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.
2
Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, California.
3
Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California.
4
Division of Cardiology, University of Washington, Seattle, Washington.
5
Department of Anesthesia, Stanford University School of Medicine, Stanford, California.
6
Palo Alto Veterans Affairs Health Care System, Palo Alto, California.

Abstract

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.

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