PDF(Pubmed)
Abstract：
Antiviral therapies for treatment of COVID-19 may be associated with significant proarrhythmic potential. In the present study, the potential cardiotoxic side effects of these therapies were evaluated using a Langendorff model of the isolated rabbit heart. 51 hearts of female rabbits were retrogradely perfused, employing a Langendorff-setup. Eight catheters were placed endo- and epicardially to perform an electrophysiology study, thus obtaining cycle length-dependent action potential duration at 90% of repolarization (APD90), QT intervals and dispersion of repolarization. After generating baseline data, the hearts were assigned to four groups: In group 1 (HXC), hearts were treated with 1 µM hydroxychloroquine. Thereafter, 3 µM hydroxychloroquine were infused additionally. Group 2 (HXC + AZI) was perfused with 3 µM hydroxychloroquine followed by 150 µM azithromycin. In group 3 (LOP) the hearts were perfused with 3 µM lopinavir followed by 5 µM and 10 µM lopinavir. Group 4 (REM) was perfused with 1 µM remdesivir followed by 5 µM and 10 µM remdesivir. Hydroxychloroquine- and azithromycin-based therapies have a significant proarrhythmic potential mediated by action potential prolongation and an increase in dispersion. Lopinavir and remdesivir showed overall significantly less pronounced changes in electrophysiology. In accordance with the reported bradycardic events under remdesivir, it significantly reduced the rate of the ventricular escape rhythm.
摘要：
用于治疗COVID-19的抗病毒疗法可能与显著的心律失常潜力有关。在本研究中,使用离体兔心脏的Langendorff模型评估了这些疗法的潜在心脏毒性副作用.对51颗雌性兔子的心脏进行了逆行灌注，采用Langendorff设置。在心内膜和心外膜放置了八根导管以进行电生理研究，从而获得90%复极化时的周期长度依赖性动作电位持续时间(APD90)，QT间期和复极化色散。生成基线数据后，将心脏分为四组：在第1组（HXC）中，心脏用1µM羟氯喹治疗。此后,另外输注3µM羟氯喹。第2组(HXC+AZI)灌注3µM羟氯喹,然后灌注150µM阿奇霉素。在第3组（LOP）中，心脏灌注3µM洛匹那韦，然后灌注5µM和10µM洛匹那韦。第4组（REM）灌注1µMremdesivir，然后灌注5µM和10µMremdesivir。基于羟氯喹和阿奇霉素的疗法具有由动作电位延长和分散度增加介导的显着心律失常潜力。洛匹那韦和remdesivir在电生理方面的总体变化明显不明显。根据remdesivir报告的心动过缓事件，它显著降低了室性逃逸心律的发生率。
