In vivo and cellular antiarrhythmic and cardiac electrophysiological effects of desethylamiodarone in dog cardiac preparations

Kohajda, Zsófia; Virág, László; Hornyik, Tibor; Husti, Zoltán; Sztojkov‐Ivanov, Anita; Nagy, Norbert; Horváth, András; Varga, Richárd; Prorok, János; Szlovák, Jozefina; Tóth, Noémi; Gazdag, Péter; Topál, Leila; Naveed, Muhammad; Árpádffy-Lovas, Tamás; Pászti, Bence; Magyar, Tibor; Koncz, István; Déri, Szilvia; Demeter-Haludka, Vivien; Aigner, Zoltán; Ördög, Balázs; Pátfalusi, M; Tálosi, László; Tiszlavicz, László; Földesi, Imre; Jost, Norbert; Baczkó, István; Varró, András

doi:10.1111/bph.15812

Cited by 2 publications

(1 citation statement)

References 40 publications

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“…In both the  and  models, we found that most of the currents were only slightly impacted by the addition of the SK current, with the exception of the rapidly activating delayed rectifier K + current (𝐼 Kr ), which showed a reduction in peak value of 15% and 10% in the  and  models, respectively, and of 𝐼 Ks , which showed a peak reduction of 35% and 31% in the  and  models, respectively. Nonetheless, the values of these two currents in the original and modified models were relatively especially compared to the wide range of physiological variability reported in experiments, up 13% for Kr and 27% 𝐼 [42] (Fig. 18S in the Material).…”

Section: Discussionmentioning

confidence: 73%

Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: A computational study

Celotto

Sánchez

Mountris

et al. 2023

Computers in Biology and Medicine

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Section: Discussionmentioning

confidence: 73%

Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: A computational study

Celotto

Sánchez

Mountris

et al. 2023

Computers in Biology and Medicine

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Amiodarone prevents wave front-tail interactions in patients with heart failure: an in silico study

Gray,

Franz

2023

American Journal of Physiology-Heart and Circulatory Physiology

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Background: Amiodarone (AM) is an anti-arrhythmic drug whose chronic use has proved effective in preventing ventricular arrhythmias in a variety of patient populations, including those with heart failure. AM has both Class III (i.e., it prolongs the action potential duration, APD, via blocking potassium channels) and Class I (i.e., it affects the rapid sodium channel) properties; however, the specific mechanism(s) by which it prevents reentry formation in HF patients remain unknown. Objective: To test the hypothesis that AM prevents reentry induction in HF during programmed electrical stimulation (PES) via its ability to induce post-repolarization refractoriness (PRR) via its Class I effects on sodium channels. Results: Here we extend our previous human action potential model to represent the effects of both HF and AM separately by calibrating to human tissue and clinical PES data respectively. We then combine these models (HF+AM) to test our hypothesis. Results from simulations in cells and cables suggest that AM acts to increase PRR and decrease the elevation of take-off potential. The ability of AM to prevent reentry was studied in-silico in two-dimensional sheets in which a variety of APD gradients (ΔAPD) were imposed. Reentrant activity was induced in all HF simulations but was prevented in 23 of 24 HF+AM models. Eliminating the AM-induced slowing of the recovery of inactivation of the sodium channel restored the ability to induce reentry. Conclusions: In-silico testing suggests that chronic AM treatment prevents reentry induction in HF patients during PES via its Class I effect to induce PRR.

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In vivo and cellular antiarrhythmic and cardiac electrophysiological effects of desethylamiodarone in dog cardiac preparations

Abstract: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Cited by 2 publications

References 40 publications

Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: A computational study

Steady-state and transient effects of SK channel block and adrenergic stimulation to counteract acetylcholine-induced arrhythmogenic effects in the human atria: A computational study

Amiodarone prevents wave front-tail interactions in patients with heart failure: an in silico study

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