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

Publisher: Humana Press Country of Publication: United States NLM ID: 101135818 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0259 (Electronic) Linking ISSN: 15307905 NLM ISO Abbreviation: Cardiovasc Toxicol Subsets: MEDLINE

Original Publication: Totowa, NJ : Humana Press, c2001-

Antiviral Agents*/pharmacology ; Antiviral Agents*/toxicity ; Isolated Heart Preparation* ; Action Potentials*/drug effects; Animals ; Rabbits ; Female ; COVID-19 Drug Treatment ; Hydroxychloroquine/toxicity ; Hydroxychloroquine/pharmacology ; Arrhythmias, Cardiac/chemically induced ; Arrhythmias, Cardiac/physiopathology ; Cardiotoxicity ; Alanine/analogs & derivatives ; Alanine/pharmacology ; Heart Rate/drug effects ; Adenosine Monophosphate/analogs & derivatives ; Adenosine Monophosphate/toxicity ; Adenosine Monophosphate/pharmacology ; Heart/drug effects

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 (APD 90 ), 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.
(© 2024. The Author(s).)

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Keywords: Anitviral; Arrhythmia; Azithromycin; Hydroxychloroquine; Long QT syndrome; Lopinavir; Remdesivir; Sudden cardiac death

0 (Antiviral Agents)
4QWG6N8QKH (Hydroxychloroquine)
OF5P57N2ZX (Alanine)
415SHH325A (Adenosine Monophosphate)
3QKI37EEHE (remdesivir)

Date Created: 20240608 Date Completed: 20240627 Latest Revision: 20241211

20241211

PMC11211193

10.1007/s12012-024-09872-3

38851664