An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics

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. Accepted for publication July 26, 2018. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (https://ift.tt/KegmMq). Funding: This research was supported by the Canadian Institutes of Health Research Fellowship (201411MFE-338745-169197 to A.C.Y.C.); the Baxter Foundation and National Institutes of Health (AG044815 and AR063963 to H.M.B.); and Stanford University Department of Anesthesia Field of anesthesia Investigator Departmental benefit Leverage for external research dollars (FIDL) Grant, Stanford University SPARK Drug Discovery Program, and Stanford University Children's Health Research Initiative to M.F.D. and E.J.B. Reprints will not be available from the authors. Address correspondence to Alex C. Y. Chang, PhD, Stanford University, 269 Campus Dr, CCSR Building, Room 3200, Stanford, CA 94305-5175. Address e-mail to acychang@stanford.edu; and Edward J. Bertaccini, MD, Department of Anesthesia, 112A Palo Alto Veterans Affairs Health Care System, Palo Alto Division, 3801 Miranda Ave, Palo Alto, CA 94304. Address e-mail to edward.Bertaccini@va.gov. © 2018 International Anesthesia Research Society

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