Consortional main: In vitro (molecular, ion channel and cellular) and in vivo investigations for the elucidation of antiarrhythmic and proarrhythmic mechanisms: the role of the repolarization reserve  Page description

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Details of project

 
Identifier
104331
Type NK
Principal investigator Varró, András
Title in Hungarian Konzorcium, fő p.: In vitro (molekuláris, ion-csatorna és sejtszintű) és in vivo szintű vizsgálatok antiaritmiás és proaritmiás mechanizmusok tisztázására: a repolarizációs rezerv szerepe
Title in English Consortional main: In vitro (molecular, ion channel and cellular) and in vivo investigations for the elucidation of antiarrhythmic and proarrhythmic mechanisms: the role of the repolarization reserve
Keywords in Hungarian celluláris elektrofiziológia, repolarizáció, proaritmia, gyógyszerbiztonság
Keywords in English cellular electrophysiology, repolarization, proarrhythmia, safety pharmacology
Discipline
Analysis, modelling and simulation of biological systems (Council of Medical and Biological Sciences)75 %
Experimental pharmacology, drug discovery and design (Council of Medical and Biological Sciences)20 %
Animal biotechnology (Council of Complex Environmental Sciences)5 %
Panel Physiology, Pathophysiology, Pharmacology and Endocrinology
Department or equivalent Department of Pharmacology and Pharmacotherapy (University of Szeged)
Participants Bányász, Tamás
Hegyi, Bence
Horváth, András
Horváth, Balázs
Husti, Zoltán
Koncz, István
Kovács, Mária
Leprán, István
Márton, Zoltán
Morvay, Nikolett
Nagy, Norbert
Nagy, Zsófia
Nánási, Péter Pál
Ördög, Balázs
Orosz, Andrea
Ruzsnavszky, Ferenc
Szél, Tamás
Szepesi, Judit
Tóth, András
Váczi, Krisztina
Virág, László
Starting date 2012-10-01
Closing date 2017-03-31
Funding (in million HUF) 87.834
FTE (full time equivalent) 28.15
state running project





 

Final report

 
Results in Hungarian
A hirtelen szívhalál kialakulásban szerepet játszanak a különböző repolarizációs zavarok talaján kialakuló szívritmuszavarok, amelyeket számos olyan tényező befolyásol, mint az élsport okozta remodelling, gyógyszeres kezelések proaritmiás mellékhatásai, különböző betegségek, iszkémiás eredetű zavarok a Ca2+-háztartásban. A projekt során 6 altémában végeztünk kísérletes munkát, amely során jelentős eredményeket értünk el. 1) Egy saját kifejlesztésű hatékony telemetriás alapú eljárás segítségével sporttevékenység közben is monitoroztuk a sportolókat, és humán és állatkísérletes modellekben kimutattuk, hogy az extrém fizikai tevékenység következtében alakul ki a sportszív, amely megváltoztathatja a repolarizációt befolyásoló áramokat, és aritmiára hajlamosítják a szívet. 2) Új hatékony eljárást dolgoztunk ki, amely segítségével in vitro, ex vivo és in vivo körülmények között sokkal megbízhatóbban vizsgálni tudjuk a különböző szerek proaritmiás hatásait. 3) Kidolgoztunk és szabadalmaztattunk egy új transzgenikus LQT5 nyúlmodellt. 4) Megvizsgáltuk a nátrium-kalcium cseremechanizmus (NCX) élet és kórtani szerepét. Új saját fejlesztésű és szabadalmaztatott NCX gátlók segítségével kimutattuk, hogy az NCX gátlása jelentős antiaritmiás hatással rendelkezik. A projekthez kapcsolódó kísérletes munkát 45 tudományos dolgozatban publikáltuk (kumulatív impakt faktor 145). A projekt során 2 MTA doktori és 15 PhD doktori értekezés és védés történt a kiterjedt kooperációs munka eredményeképpen.
Results in English
In the developing of the sudden cardiac death may play role the cardiac arrhythmias provoked by repolarization abnormalities, influenced by different factors as remodelling caused by professional sport, proarrhythmic effects of drugs, several diseases, ischaemic disorders in Ca 2+-homeostasis. We have performed our research divided in 6 subtasks, and we have obtained significant results. 1) By applying a self-developed novel telemetric monitoring system, we demonstrated that the athlete’s heart - caused by the extreme physical training- may alter the repolarizing currents and increase the arrhythmogenesis of the heart. 2. We have developed a novel and reliable method, which make possible the in vitro, ex vivo or in vivo investigation of the proarrhythmic effect of drugs. 3) We developed and patented a novel transgenic LQT5 rabbit model. 4) We have investigated the physiological and pathophysiological role of the sodium- calcium exchanger (NCX). By applying some newly patented drug developed by our group we demonstrated that the NCX-blocking effect has significant antiarrhythmic effect. The results obtained by implementing the present project have been published in 45 research papers having the cumulative impact factor of 145. During implementing the project 2 colleagues obtained their DSc degree, and 15 PhD student defended their PhD degree by presenting the research connected to this project.
Full text https://www.otka-palyazat.hu/download.php?type=zarobeszamolo&projektid=104331
Decision
Yes





 

List of publications

 
Magyar J, Kistamás K, Váczi K, Hegyi B, Horváth B, Bányász T, Nánási PP, Szentandrássy N: Concept of relative variability of cardiac action potential duration and its test under various experimental conditions, Gen Physiol Biophys 35:55-62, 2016
Horváth B, Váczi K, Hegyi B, Gönczi M, Dienes B, Kistamás K, Bányász T, Magyar J, Baczkó I, Varró A, Seprényi Gy, Csernoch L, Nánási PP, Szentandrássy N: Sarcolemmal Ca2+-entry through L-type Ca2+ channels controls the profile of Ca2+-activated Cl- current in canine ventricular myocytes, J Mol Cell Cardiol 97:125-139, 2016
Pueyo E, Dangerfield CE, Britton OJ, Virág L, Kistamas K, Szentandrassy N, Jost N, Varró A, Nanasi PP, Burrage K, Rodriguez B: Experimentally-based computational investigation into beat-to-beat variability in ventricular repolarisation and its response to ionic current inhibition, PLoS One 28;11(3):e0151461, 2016
Szentandrássy N, Horváth B, Váczi K, Kistamás K, Masuda L, Magyar J, Bányász T, Papp Z, Nánási PP: Dose-dependent electrophysiological effects of the myosin activator omecamtiv mecarbil in canine ventricular cardiomyocytes, J Physiol Pharmacol; 67:483-489, 2016
Kohajda Zs, Farkas-Morvay N, Jost N, Nagy N, Geramipour A, Horváth A, Varga RS, Hornyik T, Corici C, Acsai K, Horváth B, Prorok J, Ördög B, Déri S, Tóth D, Levijoki J, Pollesello P, Koskelainen T, Otsomaa L, Tóth A, Baczkó I, Leprán I, Nánási PP, Papp JGy, Varró A, Virág L: The effect of a novel highly selective inhibitor of the sodium/calcium exchanger (NCX) on cardiac arrhythmias in in vitro and in vivo experiments, PLoS One; 11(11):e0166041. doi: 10.1371/journal.pone.0166041, 2016
Major P, Baczkó I, Hiripi L, Odening KE, Juhász V, Kohajda Z, Horváth A, Seprényi G, Kovács M, Virág L, Jost N, Prorok J, Ördög B, Doleschall Z, Nattel S, Varró A, Bősze Z: A novel transgenic rabbit model with reduced repolarization reserve: long QT syndrome caused by a dominant-negative mutation of KCNE1 gene, Br J Pharmacol, 73(12):2046-61, 2016
Geramipour A, Kohajda Zs, Corici C, Prorok J, Szakonyi Zs, Oravecz K, Márton Z, Nagy N, Tóth A, Acsai K, Virág L, Varró A, Jost N: The investigation of the cellular electrophysiological and antiarrhythmic effects of a novel selective sodium-calcium exchanger inhibitor GYKB-6635 in canine and guinea pig hearts, Can J Physiol Pharmacol, 94(10), 1090-1101, 2016
Baczkó I, Jost N, Virág L, Bősze Zs, Varró A: Rabbit models as tools for preclinical cardiac electrophysiological safety testing: importance of repolarization reserve, Prog Biophys Mol Biol. 121(2):157-68, 2016
Bősze Z, Major P, Baczkó I, Odening KE, Bodrogi L, Hiripi L, Varró A: The potential impact of new generation transgenic methods on creating rabbit models of cardiac diseases., Prog Biophys Mol Biol. 21(2):123-30, 2016
Papp H, Sarusi A, Farkas AS, Takacs H, Kui P, Vincze D, Ivany E, Varro A, Papp JG, Forster T, Farkas A: Hyperventilation assists proarrhythmia development during delayed repolarization in clofilium-treated, anaesthetized, mechanically ventilated rabbits, J Physiol Pharmacol. 67(5):731-737., 2016
Kui P, Orosz S, Takács H, Sarusi A, Csík N, Rárosi F, Csekő C, Varró A, Papp JG, Forster T, Farkas AS, Farkas A: New in vitro model for proarrhythmia safety screening: IKs inhibition potentiates the QTc prolonging effect of IKr inhibitors in isolated guinea pig hearts, J Pharmacol Toxicol Methods. 80:26-34, 2016
Szentmiklósi AJ, Szentandrássy N, Hegyi B, Horváth B, Magyar J, Bányász T, Nánási PP: Chemistry, physiology, and pharmacology of β-adrenergic mechanisms in the heart. Why are β-blocker antiarrhythmics superior?, Curr Pharm Design, 21(8):1030-1041, 2015
Szentandrassy N, Nagy D, Hegyi B, Magyar J, Bányász T, Nánási PP: Class IV antiarrhythmic agents: new compounds using an old strategy, Curr Pharm Design, 21(8):977-1010, 2015
Magyar J, Bányász T, Szentandrássy N, Kistamás K, Nánási PP, Satin J: Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias., Curr Pharm Design, 21(8):1042-1052, 2015
Váczi K, Hegyi B, Ruzsnavszky F, Kistamás K, Horváth B, Bányász T, Nánási PP, Szentandrássy N, Magyar J: 9-anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential, Naunyn Schmiedeberg's Arch Pharmacol, 388(1):87-100, 2015
Szentandrássy N, Kistamás K, Hegyi B, Horváth B, Ruzsnavszky F, Váczi K, Magyar J, Bányász T, Varró A, Nánási PP: Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes, Pflugers Arch., Eur J Physiol, 467(7):1431-1443, 2015
Szentmiklosi AJ, Galajda Z, Cseppento Á, Gesztelyi R, Susán Z, Hegyi B, Nánási PP: The Janus face of adenosine: antiarrhythmic and proarrhythmic actions, Curr Pharm Design, 21(8):965-976, 2015
Kistamás K, Hegyi B, Váczi K, Horváth B, Bányász T, Magyar J, Szentandrássy N, Nánási PP.: Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration., Can J Physiol Pharmacol. 93(7):563-568, 2015
Horváth B, Hegyi B, Kistamás K, Váczi K, Bányász T, Magyar J, Szentandrássy N, Nánási PP: Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes., Can J Physiol Pharmacol. 93(7):527-534, 2015
Kistamas K, Szentandrassy N, Hegyi B, Vaczi K, Ruzsnavszky F, Horvath B, Banyasz T, Nanasi PP, Magyar J.: Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes., J Physiol Pharmacol. 66(1):73-81, 2015
Orvos P, Virág L, Tálosi L, Hajdú Z, Csupor D, Jedlinszki N, Szél T, Varró A, Hohmann J: Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential - a safety approach, Fitoterapia. 100:156-165, 2015
Szepesi J, Acsai K, Sebok Z, Prorok J, Pollesello P, Levijoki J, Papp JG, Varro A, Toth A: Comparison of the efficiency of Na+/Ca2+ exchanger or Na+/H+ exchanger inhibition and their combination in reducing coronary reperfusion-induced arrhythmias, J Physiol Pharmacol, 66(2):215-226., 2015
Orosz A, Csajbók É, Czékus C, Gavallér H, Magony S, Valkusz Z, Várkonyi TT, Nemes A, Baczkó I, Forster T, Wittmann T, Papp JG, Varró A, Lengyel: Increased short-term beat-to-beat variability of QT interval in patients with acromegaly, PLoS One. 10(4):e0125639. doi: 10.1371/journal.pone.0125639., 2015
Ördög B, Hategan L, Kovács M, Seprényi G, Kohajda Z, Nagy I, Hegedűs Z, Környei L, Jost N, Katona M, Szekeres M, Forster T, Papp JG, Varró A, Sepp R: Identification and functional characterisation of a novel KCNJ2 mutation, Val302del, causing Andersen-Tawil syndrome, Can J Physiol Pharmacol, 93(7):569-575, 2015
Nagy N, Szél T, Jost N, Tóth A, Gy Papp J, Varró A: Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart, Can J Physiol Pharmacol, 93(9):803-810, 2015
Morvay N, Baczkó I, Sztojkov-Ivanov A, Falkay G, Papp JG, Varró A, Leprán I: Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats, Can J Physiol Pharmacol, 93(9):773-777, 2015
Jost N, Kohajda Zs, Corici C, Horvath A, Bitay M, Bogats G, Papp JGy, Varro A, Virag L: The comparative study of rapid and slow delayed rectifier currents in undiseased human, dog, rabbit and guinea pig ventricular myocytes., Europace, 15 (suppl 2): ii1-ii9, doi: 10.1093/europace/eut170, 2013
Kohajda Zs, A Horvath, J Levijoki, P Pollesello, T Koskelainen, L Otsomaa, AP Koivisto, JGy Papp, A Varró, L Virág: Cellular electrophysiological and antiarrhythmic efficacy of new sodium/calcium exchanger inhibitors in the canine heart., Europace, 15 (suppl 2): ii1-ii9, doi: 10.1093/europace/eut170, 2013
Kristóf A, Husti Z, Koncz I, Kohajda Z, Szél T, Juhász V, Biliczki P, Jost N, Baczkó I, Papp JGy, Varró A, Virág L: Diclofenac prolongs repolarization in ventricular muscle with impaired repolarization reserve, PLoS ONE 7(12): e53255. doi:10.1371/journal.pone.0053255, 2013
Corici C, Kohajda Z, Kristóf A, Horváth A,Virág L, Szél T, Nagy N, Szakonyi Zs, Fülöp F, Muntean DM, Varró A, Jost N: R-L3 enantiomers have adverse modulating effects on IKs in rabbit ventricular myocytes., Canadian Journal of Physiology and Pharmacology, 91(8), 586-592, 2013
Szűts V, Ménesi Z, Varga-Orvos Z, Zvara A, Houshmand N, Bitay M, Bogáts G, Virág L, Baczkó I, Szalontai B, Geramipoor A, Cotella D, Wettwer E, Ravens U, Deák F, Puskás LG, Papp, JG, Kiss I, Varró A, Jost N: Altered expression of genes for Kir ion channels in dilated cardiomyopathy., Canadian Journal of Physiology and Pharmacology, 91(8), 648-656, 2013
Jost N, Nagy N, Corici C, Kohajda Z, Horváth A, Acsai K, Biliczki P, Levijoki J, Pollesello P, Koskelainen T, Otsomaa L, Toth A, Papp JGy, Varró A, Virág L: ORM-10103, a novel specific inhibitor of the sodium/calcium exchanger, decreases early and delayed afterdepolarization in the canine heart, British Journal of Pharmacology, 170, 768-778, 2013
Jost N, Virág L, Comtois P, Ördög B, Szűts V, Seprényi Gy, Bitay M, Kohajda Zs, Koncz I, Nagy N, Szél T, Magyar J, Kovács M, Puskás LG, Lengyel Cs, Wettwer E, Ravens U, Nanasi PP, Papp JGy, Varró A, Nattel S: Ionic mechanisms limiting cardiac repolarization-reserve in humans compared to dogs, Journal of Physiology, 591 (17), 4189–4206, 2013
Nagy N, Acsai K, Kormos A, Sebők Zs, Farkas AS, Jost N, Nánási PP, Papp JGy, Varró A, Tóth A: [Ca2+]i-induced augmentation of the inward rectifier potassium current (IK1) in canine and human ventricular myocardium., Pflügers Archiv - European Journal of Physiology, 465, 1621–1635, 2013
Hegyi B, Komáromi I, Kistamás K, Ruzsnavszky F, Váczi K, Horváth B, Magyar J, Bányász T, Nánási PP, Szentandrássy N.: Tetrodotoxin blockade on canine cardiac L-type Ca²⁺ channels depends on pH and redox potential., Marine Drugs, 11(6), 2140-2153, 2013
Katter K, Geurts AM, Hoffmann O, Mátés L, Landa V, Hiripi L, Moreno C, Lazar J, Bashir S, Zidek V, Popova E, Jerchow B, Becker K, Devaraj A, Walter I, Grzybowksi M, Corbett M, Filho AR, Hodges MR, Bader M, Ivics Z, Jacob HJ, Pravenec M, Bosze Z, Rülicke T, Izsvák Z: Transposon-mediated transgenesis, transgenic rescue, and tissue-specific gene expression in rodents and rabbits, FASEB J, 27(3):930-934, 2013
Szentandrássy N, Papp F, Hegyi B, Krasznai Z, Nánási PP: Tetrodotoxin blocks native cardiac L-type Ca2+ channels but not Cav1.2 channels expressed in HEK cells, J Physiol Pharmacol, 64:807-810, 2014
Ruzsnavszky F, Hegyi B, Kistamás K, Váczi K, Horváth B, Szentandrássy N, Bányász T, Nánási PP, Magyar J: Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes., Naunyn Schmiedeberg's Arch Pharmacol , 387:457-467, 2014
Szentandrássy N, Kistamás K, Hegyi B, Horváth B, Ruzsnavszky F, Váczi K, Magyar J, Bányász T, Varró A, Nánási PP:: Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes, Pflügers Archiv Eur J Physiol, epub, 2014
Szentmiklósi AJ, Szentandrássy N, Hegyi B, Horváth B, Magyar J, Bányász T, Nánási PP: Chemistry, physiology, and pharmacology of β-adrenergic mechanisms in the heart. Why are β-blocker antiarrhythmics superior?, Curr Pharm Design, epub, 2014
Szentandrassy N, Nagy D, Hegyi B, Magyar J, Bányász T, Nánási PP: Class IV antiarrhythmic agents: new compounds using an old strategy, Curr Pharm Design, epub, 2014
Magyar J, Bányász T, Szentandrássy N, Kistamás K, Nánási PP, Satin J: Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias., Curr Pharm Design, epub,, 2014
Váczi K, Hegyi B, Ruzsnavszky F, Kistamás K, Horváth B, Bányász T, Nánási PP, Szentandrássy N, Magyar J: 9-anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential., Naunyn Schmiedeberg's Arch Pharmacol, 387:457-467, 2014
Baczko I, Liknes D, Yang W, Hamming KC, Searle G, Jaeger K, Husti Z, Juhasz V, Klausz G, Pap R, Saghy L, Varro A, Dolinsky V, Wang S, Rauniyar V, Hall D, Dyck JR, Light PE: Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation., Br J Pharmacol., 171(1):92-106, 2014
Kormos A, Nagy N, Acsai K, Váczi K, Ágoston S, Pollesello P, Levijoki J, Szentandrássy N, Papp JG, Varró A, Tóth A.: Efficacy of selective NCX inhibition by ORM-10103 during simulated ischemia/reperfusion., Eur J Pharmacol. 5;740:539-551, 2014
Orosz S, Sarusi A, Csík N, Papp JG, Varró A, Farkas S, Forster T, Farkas AS, Farkas A.: Assessment of efficacy of proarrhythmia biomarkers in isolated rabbit hearts with attenuated repolarization reserve., J Cardiovascular Pharmacol, 64(3):266-276, 2014
Sarusi A, Rárosi F, Szűcs M, Csík N, Farkas AS, Papp JG, Varró A, Forster T, Curtis MJ, Farkas A.: Absolute beat-to-beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia-induced ventricular fibrillation., Br J Pharmacol. 171(7):1772-82, 2014
Szentandrássy N, Kistamás K, Hegyi B, Horváth B, Ruzsnavszky F, Váczi K, Magyar J, Bányász T, Varró A, Nánási PP.: Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes., Pflugers Arch., Eur J Physiol, epub, 2014
Ivics Z, Hiripi L, Hoffmann OI, Mátés L, Yau TY, Bashir S, Zidek V, Landa V, Geurts A, Pravenec M, Rülicke T, Bösze Z, Izsvák Z.: Germline transgenesis in rabbits by pronuclear microinjection of Sleeping Beauty transposons., Nat Protoc. 9(4):794-809, 2014
Szentandrássy N, Papp F, Hegyi B, Krasznai Z, Nánási PP: Tetrodotoxin blocks native cardiac L-type Ca2+ channels but not Cav1.2 channels expressed in HEK cells, J Physiol Pharmacol, 64:807-810, 2014
Ruzsnavszky F, Hegyi B, Kistamás K, Váczi K, Horváth B, Szentandrássy N, Bányász T, Nánási PP, Magyar J: Asynchronous activation of calcium and potassium currents by isoproterenol in canine ventricular myocytes., Naunyn Schmiedeberg's Arch Pharmacol , 387:457-467, 2014
Szentandrássy N, Kistamás K, Hegyi B, Horváth B, Ruzsnavszky F, Váczi K, Magyar J, Bányász T, Varró A, Nánási PP:: Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes, Pflügers Archiv Eur J Physiol, 467(7):1431-1443, 2014
Szentmiklósi AJ, Szentandrássy N, Hegyi B, Horváth B, Magyar J, Bányász T, Nánási PP: Chemistry, physiology, and pharmacology of β-adrenergic mechanisms in the heart. Why are β-blocker antiarrhythmics superior?, Curr Pharm Design, 21(8):1030-1041, 2015
Szentandrassy N, Nagy D, Hegyi B, Magyar J, Bányász T, Nánási PP: Class IV antiarrhythmic agents: new compounds using an old strategy, Curr Pharm Design, 21(8):977-1010, 2015
Magyar J, Bányász T, Szentandrássy N, Kistamás K, Nánási PP, Satin J: Role of gap junction channel in the development of beat-to-beat action potential repolarization variability and arrhythmias., Curr Pharm Design, 21(8):1042-1052, 2015
Váczi K, Hegyi B, Ruzsnavszky F, Kistamás K, Horváth B, Bányász T, Nánási PP, Szentandrássy N, Magyar J: 9-anthracene carboxylic acid is more suitable than DIDS for characterization of calcium-activated chloride current during canine ventricular action potential., Naunyn Schmiedeberg's Arch Pharmacol, 387:457-467, 2014
Baczko I, Liknes D, Yang W, Hamming KC, Searle G, Jaeger K, Husti Z, Juhasz V, Klausz G, Pap R, Saghy L, Varro A, Dolinsky V, Wang S, Rauniyar V, Hall D, Dyck JR, Light PE: Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation., Br J Pharmacol., 171(1):92-106, 2014
Kormos A, Nagy N, Acsai K, Váczi K, Ágoston S, Pollesello P, Levijoki J, Szentandrássy N, Papp JG, Varró A, Tóth A.: Efficacy of selective NCX inhibition by ORM-10103 during simulated ischemia/reperfusion., Eur J Pharmacol. 5;740:539-551, 2014
Orosz S, Sarusi A, Csík N, Papp JG, Varró A, Farkas S, Forster T, Farkas AS, Farkas A.: Assessment of efficacy of proarrhythmia biomarkers in isolated rabbit hearts with attenuated repolarization reserve., J Cardiovascular Pharmacol, 64(3):266-276, 2014
Sarusi A, Rárosi F, Szűcs M, Csík N, Farkas AS, Papp JG, Varró A, Forster T, Curtis MJ, Farkas A.: Absolute beat-to-beat variability and instability parameters of ECG intervals: biomarkers for predicting ischaemia-induced ventricular fibrillation., Br J Pharmacol. 171(7):1772-82, 2014
Szentandrássy N, Kistamás K, Hegyi B, Horváth B, Ruzsnavszky F, Váczi K, Magyar J, Bányász T, Varró A, Nánási PP.: Contribution of ion currents to beat-to-beat variability of action potential duration in canine ventricular myocytes., Pflugers Arch., Eur J Physiol, 467(7):1431-1443, 2015
Ivics Z, Hiripi L, Hoffmann OI, Mátés L, Yau TY, Bashir S, Zidek V, Landa V, Geurts A, Pravenec M, Rülicke T, Bösze Z, Izsvák Z.: Germline transgenesis in rabbits by pronuclear microinjection of Sleeping Beauty transposons., Nat Protoc. 9(4):794-809, 2014
Szentmiklosi AJ, Galajda Z, Cseppento Á, Gesztelyi R, Susán Z, Hegyi B, Nánási PP.: The Janus face of adenosine: antiarrhythmic and proarrhythmic actions., Curr Pharm Design, 21(8):965-976, 2015
Kistamás K, Hegyi B, Váczi K, Horváth B, Bányász T, Magyar J, Szentandrássy N, Nánási PP.: Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration., Can J Physiol Pharmacol. 93(7):563-568, 2015
Horváth B, Hegyi B, Kistamás K, Váczi K, Bányász T, Magyar J, Szentandrássy N, Nánási PP: Cytosolic calcium changes affect the incidence of early afterdepolarizations in canine ventricular myocytes., Can J Physiol Pharmacol. 93(7):527-534, 2015
Kistamas K, Szentandrassy N, Hegyi B, Vaczi K, Ruzsnavszky F, Horvath B, Banyasz T, Nanasi PP, Magyar J.: Changes in intracellular calcium concentration influence beat-to-beat variability of action potential duration in canine ventricular myocytes., J Physiol Pharmacol. 66(1):73-81, 2015
Nagy N, Kormos A, Kohajda Z, Szebeni Á, Szepesi J, Pollesello P, Levijoki J, Acsai K, Virág L, Nánási PP, Papp JG, Varró A, Tóth A.: Selective Na(+) /Ca(2+) exchanger inhibition prevents Ca(2+) overload-induced triggered arrhythmias., Br J Pharmacol, 171(24):5665-81, 2014
Orvos P, Virág L, Tálosi L, Hajdú Z, Csupor D, Jedlinszki N, Szél T, Varró A, Hohmann J.: Effects of Chelidonium majus extracts and major alkaloids on hERG potassium channels and on dog cardiac action potential - a safety approach., Fitoterapia. 100:156-165, 2015
Szepesi J, Acsai K, Sebok Z, Prorok J, Pollesello P, Levijoki J, Papp JG, Varro A, Toth A.: Comparison of the efficiency of Na+/Ca2+ exchanger or Na+/H+ exchanger inhibition and their combination in reducing coronary reperfusion-induced arrhythmias., J Physiol Pharmacol, 66(2):215-226., 2015
Orosz A, Csajbók É, Czékus C, Gavallér H, Magony S, Valkusz Z, Várkonyi TT, Nemes A, Baczkó I, Forster T, Wittmann T, Papp JG, Varró A, Lengyel C.: Increased Short-Term Beat-To-Beat Variability of QT Interval in Patients with Acromegaly., PLoS One. 10(4):e0125639. doi: 10.1371/journal.pone.0125639., 2015
Husti Z, Tábori K, Juhász V, Hornyik T, Varró A, Baczkó I.: Combined inhibition of key potassium currents has different effects on cardiac repolarization reserve and arrhythmia susceptibility in dogs and rabbits., Can J Physiol Pharmacol, 93(7):535-544, 2015
Ördög B, Hategan L, Kovács M, Seprényi G, Kohajda Z, Nagy I, Hegedűs Z, Környei L, Jost N, Katona M, Szekeres M, Forster T, Papp JG, Varró A, Sepp R.: Identification and functional characterisation of a novel KCNJ2 mutation, Val302del, causing Andersen-Tawil syndrome., Can J Physiol Pharmacol, 93(7):569-575, 2015
Orosz A, Baczkó I, Nagy V, Gavallér H, Csanády M, Forster T, Papp JG, Varró A, Lengyel C, Sepp R: Short-term beat-to-beat variability of the QT interval is increased and correlates with parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyo, Can J Physiol Pharmacol, 93(9):765-772, 2015
Nagy N, Szél T, Jost N, Tóth A, Gy Papp J, Varró A.: Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart., Can J Physiol Pharmacol, 93(9):803-810, 2015
Morvay N, Baczkó I, Sztojkov-Ivanov A, Falkay G, Papp JG, Varró A, Leprán I.: Long-term pretreatment with desethylamiodarone (DEA) or amiodarone (AMIO) protects against coronary artery occlusion induced ventricular arrhythmias in conscious rats., Can J Physiol Pharmacol, 93(9):773-777, 2015




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