Electrophysiological Profile of Different Antiviral Therapies in a Rabbit Whole-Heart Model

TL;DR

This study evaluates the heart risks of antiviral drugs used for COVID-19 in rabbit hearts, finding that some treatments increase arrhythmia risk.

Contribution

The study provides new electrophysiological data on the cardiotoxic effects of antiviral therapies in an isolated rabbit heart model.

Findings

Hydroxychloroquine and azithromycin significantly increased proarrhythmic potential through action potential prolongation.

Lopinavir and remdesivir caused less pronounced electrophysiological changes compared to hydroxychloroquine-based therapies.

Remdesivir significantly reduced ventricular escape rhythm rate, consistent with reported bradycardic events.

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.

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