Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

ORANGE FLAVONOID HESPERETIN PROLONGED ACTION POTENTIAL DURATION AND INHIBITS THE SLOW DELAYED RECTIFIER POTASSIUM CURRENT (IKs) IN DOG AND RABBIT CARDIAC VENTRICULAR MUSCLE PREPARATIONS AND ISOLATED MYOCYTES A. S. A. Mohammed 1 , M. Naveed 1 , L. Topal 1 , G. Mohácsi 2 , J. Prorok 1 , I. Baczkó 1 , L. Virág 1 , N. Jost 1,3 , A. Varró 1,3 1 University of Szeged Albert Szent- Györgyi Faculty of Medicine, Department of Pharmacology and Pharmacotherapy, Szeged, Hungary; 2 University of Szeged, Hungary; 3 ELKH-SZTE Research Group of Cardiovascular Pharmacology, Szeged, Hungary Background: Hesperetin is the main flavonoid in oranges and can be found in orange juice at concentrations up to 720 mmol/L. It was stated that a high intake of dietary flavonoids, which are abundant in fruits, tea ,vegetables, and wine, is known to reduce cardiovascular mortality, however, the effects of flavonoids on cardiac electrophysiology may have both antiarrhythmic and proarrhythmic consequences as they can attenuate the repolarization reserve. Aim: The combined effect of Hesperetin and IKr-blocking antiarrhythmic drugs on action potential duration (APD) has not been studied. Therefore, the present work aimed to study the additive inhibitory effect of Hesperetin on the repolarization of the action potential in dog and rabbit ventricular preparations with normal and attenuated repolarization reserve. The effects of the drug on transmembrane slow delayed rectifier K + currents (IKs) were also investigated. Method: Action potentials were recorded in right ventricular trabecular and papillary muscle preparations obtained from dog and rabbit hearts using conventional microelectrode techniques. The repolarization reserve was attenuated using the IKr blocker Dofetilide and the late Na + channel activator Veratrine. Transmembrane (IKs) were measured using the whole-cell configuration of the patch-clamp technique at 37℃. Results and discussion: This study is the first to evaluate the combined effect of Hesperetin with IKr - blocking antiarrhythmic drugs on ventricle APD. Hesperetin 10 µM alone has no notable effect on APD, however, applying 10µM hesperetin after attenuating the repolarization reserve by using Dofetilide 100nM and Veratrine 50 µg caused significant prolongation of the steady APD (from 466±18 ms to 512±23 ms (n=10)). In agreement with action potential duration data, a moderate but statistically significant effect of 10 and 30 µM was observed in the magnitude of tran smembrane IKs. Conclusion: Hesperetin alone has no or negligible effect on action potential duration, therefore the risk of arrhythmia is low for healthy people. However; if the repolarization reserve has been attenuated due to some pathological conditions such as heart failure or some variable abnormalities such as adverse effects, genetic mutations and polymorphisms, electrophysiological remodeling, and changes in serum ion concentrations; a high amount of orange juice consumption might lead to ventricular arrhythmia due to the inhibition of Iks and prolongation in the action potential duration. Funding:This work was funded by the National Research Development and Innovation Office (NKFIH K-119992, K-128851 and GINOP-2.3.2-15-2016-00006), the Ministry of Human Capacities Hungary (20391- 3/2018/FEKUSTRAT, EFOP-3.6.2-16-2017-00006-LIVE LONGER and EFOP 3.6.3-VEKOP-16-2017- 00009) and by the Hungarian Academy of Sciences. The GINOP and EFOP projects are co-financed by the European Union and the European Regional Development Fund Keywords: hesperetin , APD, IKs, repolarization reserve

97