Divergent Electrophysiological Effects of Loperamide and Naloxone in a Sensitive Whole-Heart Model

Wolfes, Julian; Ellermann, Christian; Burde, Sophie; Leitz, Patrick; Bögeholz, Nils; Willy, Kevin; Fehr, Michael; Reinke, Florian; Eckardt, Lars; Frommeyer, Gerrit

doi:10.1007/s12012-020-09616-z

Cited by 5 publications

(2 citation statements)

References 22 publications

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“…In this study, different or opposing effects on APD 90 and QT interval were observed in several groups, which may seem counterintuitive at first glance. However, this was observed more frequently by our [ 42 ] and other groups [ 43 ], as changes in dispersion or conduction velocity can cause QT time prolongation even with unchanged APD. Overall, other groups have already shown that isolated APD and QT interval are an insufficient parameters to assess drug-induced proarrhythmia [ 44 ].…”

Section: Electrophysiological Safety Of Remdesivirmentioning

confidence: 58%

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

Wolfes,

Kirchner,

Doldi

et al. 2024

Cardiovasc Toxicol

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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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Section: Electrophysiological Safety Of Remdesivirmentioning

confidence: 58%

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

Wolfes,

Kirchner,

Doldi

et al. 2024

Cardiovasc Toxicol

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“…Due to the large number of loperamide users and the increasing number of cases of loperamide poisoning, loperamide poisoning can now be treated with naloxone. However, naloxone may not effectively suppress loperamide-induced QT interval , and it has even been reported to further prolong the QT interval in patients [ 68 ]. Therefore, the current priority is to strictly control the use of loperamide and avoid drug overdose as much as possible.…”

Section: Low-addictive Opioids Also Carry Arrhythmia Riskmentioning

confidence: 99%

Opioids-Induced Long QT Syndrome: A Challenge to Cardiac Health

Hu,

Song,

Huang

et al. 2024

Cardiovasc Toxicol

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The challenge posed by opioid overdose has become a significant concern for health systems due to the complexities associated with drug prohibition, widespread clinical use, and potential abuse. In response, healthcare professionals have primarily concentrated on mitigating the hallucinogenic and respiratory depressant consequences of opioid overdose to minimize associated risks. However, it is crucial to acknowledge that most opioids possess the capacity to prolong the QT interval, particularly in cases of overdose, thereby potentially resulting in severe ventricular arrhythmias and even sudden death if timely intervention is not implemented. Consequently, alongside addressing the typical adverse effects of opioids, it is imperative to consider their cardiotoxicity. To enhance comprehension of the correlation between opioids and arrhythmias, identify potential targets for prompt intervention, and mitigate the hazards associated with clinical utilization, an exploration of the interaction between drugs and ion channels, as well as their underlying mechanisms, becomes indispensable. This review primarily concentrates on elucidating the impact of opioid drugs on diverse ion channels, investigating recent advancements in this domain, and attaining a deeper understanding of the mechanisms underlying the prolongation of the QT interval by opioid drugs, along with potential interventions.

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