An In Vitro Model for Identifying Cardiac Side Effects of Anesthetics

Anesth Analg. 2020 Jan;130(1):e1-e4. doi: 10.1213/ANE.0000000000003757.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adult
  • Anesthetics, Intravenous / toxicity*
  • Cardiotoxicity
  • Cell Line
  • Etomidate / toxicity*
  • Female
  • Heart Diseases / chemically induced*
  • Heart Diseases / pathology
  • Heart Diseases / physiopathology
  • Heart Rate / drug effects*
  • Humans
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / pathology
  • Male
  • Middle Aged
  • Myocardial Contraction / drug effects*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / pathology
  • Proof of Concept Study
  • Propofol / toxicity*
  • Risk Assessment
  • Time Factors
  • Young Adult

Substances

  • Anesthetics, Intravenous
  • Propofol
  • Etomidate