Department of Pharmacology, University of California-Davis, Davis, California, USA.
Department of Pharmacology, University of California-Davis, Davis, California, USA.
JACC Clin Electrophysiol. 2023 Dec;9(12):2642-2648. doi: 10.1016/j.jacep.2023.08.016. Epub 2023 Sep 27.
Despite evidence that women are at higher risk of drug-induced torsade de pointes and sudden cardiac death, female sex is vastly underrepresented in cardiovascular research, thus limiting our fundamental understanding of sex-specific arrhythmia mechanisms and our ability to predict arrhythmia propensity. To address this urgent clinical and preclinical need, we developed a quantitative tool that predicts the electrophysiological response to drug administration in female cardiomyocytes starting from data collected in males. We demonstrate the suitability of our translator for sex-specific cardiac safety assessment and include proof-of-concept application of our translator to in vitro and in vivo data.
尽管有证据表明女性发生药物诱导的尖端扭转型室性心动过速和心脏性猝死的风险更高，但女性在心血管研究中的代表性严重不足，这限制了我们对性别特异性心律失常机制的基本理解，也限制了我们预测心律失常倾向的能力。为了解决这一紧迫的临床前和临床需求，我们开发了一种定量工具，该工具可以根据从男性收集的数据来预测女性心肌细胞对药物给药的电生理反应。我们证明了我们的翻译器在性别特异性心脏安全性评估中的适用性，并包括我们的翻译器在体外和体内数据中的概念验证应用。
