Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study

Atrial fibrillation is the most common sustained cardiac arrhythmia. Dofetilide is an antiarrhythmic drug for the treatment of chronic AF that specifically blocks the rapid component of the delayed rectifier potassium current IKr. Dofetilide prolongs the action potential duration and QT interval in...

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Fecha de publicación:
2017
Institución:
Universidad de Medellín
Repositorio:
Repositorio UDEM
Idioma:
eng
OAI Identifier:
oai:repository.udem.edu.co:11407/4275
Acceso en línea:
http://hdl.handle.net/11407/4275
Palabra clave:
Antiarrhythmic drug
Atrial fibrillation
Dofetilide
In silico model
Biomedical engineering
Electric rectifiers
Electrophysiology
Action potential durations
Antiarrhythmic drug
Atrial fibrillation
Cardiac arrhythmia
Concentration-dependent
Dofetilide
In-silico models
Potassium currents
Diseases
Rights
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http://purl.org/coar/access_right/c_16ec
id REPOUDEM2_5d4eedccc34a47ae01a828e173723434
oai_identifier_str oai:repository.udem.edu.co:11407/4275
network_acronym_str REPOUDEM2
network_name_str Repositorio UDEM
repository_id_str
dc.title.spa.fl_str_mv Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
title Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
spellingShingle Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
Antiarrhythmic drug
Atrial fibrillation
Dofetilide
In silico model
Biomedical engineering
Electric rectifiers
Electrophysiology
Action potential durations
Antiarrhythmic drug
Atrial fibrillation
Cardiac arrhythmia
Concentration-dependent
Dofetilide
In-silico models
Potassium currents
Diseases
title_short Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
title_full Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
title_fullStr Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
title_full_unstemmed Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
title_sort Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico study
dc.contributor.affiliation.spa.fl_str_mv Tobón, C., MATBIOM, Universidad de Medellín, Medellín, Colombia
Pérez, S., Grupo de Dinámica Cardiovascular, Universidad Pontificia Bolivariana, Medellín, Colombia
Ugarte, J.P., Grupo de Dinámica Cardiovascular, Universidad Pontificia Bolivariana, Medellín, Colombia
Saiz, J., CI2B, Universitat Politècnica de València, Valencia, Spain
dc.subject.keyword.eng.fl_str_mv Antiarrhythmic drug
Atrial fibrillation
Dofetilide
In silico model
Biomedical engineering
Electric rectifiers
Electrophysiology
Action potential durations
Antiarrhythmic drug
Atrial fibrillation
Cardiac arrhythmia
Concentration-dependent
Dofetilide
In-silico models
Potassium currents
Diseases
topic Antiarrhythmic drug
Atrial fibrillation
Dofetilide
In silico model
Biomedical engineering
Electric rectifiers
Electrophysiology
Action potential durations
Antiarrhythmic drug
Atrial fibrillation
Cardiac arrhythmia
Concentration-dependent
Dofetilide
In-silico models
Potassium currents
Diseases
description Atrial fibrillation is the most common sustained cardiac arrhythmia. Dofetilide is an antiarrhythmic drug for the treatment of chronic AF that specifically blocks the rapid component of the delayed rectifier potassium current IKr. Dofetilide prolongs the action potential duration and QT interval in a concentration-dependent fashion, therefore, the risk of QT prolongation is dose related. It is important to study the electrophysiological effects of dofetilide at different concentrations in human atrial cells. For this, we simulated the effects of dofetilide on human atrial cell and studied its effect on atrial action potential under normal conditions and during cAF. We developed a model of dofetilide effects on IKrand IKACh. Our results show that dofetilide blocks both currents in a fraction greater as the concentration increases, which results in an action potential duration lengthening. To our knowledge, this is the first work that has developed mathematical models of dofetilide effects on IKrand IKAChcurrents to study its effect on human atrial action potential. © Springer Nature Singapore Pte Ltd. 2017.
publishDate 2017
dc.date.accessioned.none.fl_str_mv 2017-12-19T19:36:43Z
dc.date.available.none.fl_str_mv 2017-12-19T19:36:43Z
dc.date.created.none.fl_str_mv 2017
dc.type.eng.fl_str_mv Conference Paper
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dc.type.driver.none.fl_str_mv info:eu-repo/semantics/conferenceObject
dc.identifier.isbn.none.fl_str_mv 9789811040856
dc.identifier.issn.none.fl_str_mv 16800737
dc.identifier.uri.none.fl_str_mv http://hdl.handle.net/11407/4275
dc.identifier.doi.none.fl_str_mv 10.1007/978-981-10-4086-3_10
dc.identifier.reponame.spa.fl_str_mv reponame:Repositorio Institucional Universidad de Medellín
dc.identifier.instname.spa.fl_str_mv instname:Universidad de Medellín
identifier_str_mv 9789811040856
16800737
10.1007/978-981-10-4086-3_10
reponame:Repositorio Institucional Universidad de Medellín
instname:Universidad de Medellín
url http://hdl.handle.net/11407/4275
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.isversionof.spa.fl_str_mv https://www.scopus.com/inward/record.uri?eid=2-s2.0-85018409745&doi=10.1007%2f978-981-10-4086-3_10&partnerID=40&md5=280d9472ab3c08a89e7be6b0469e002e
dc.relation.ispartofes.spa.fl_str_mv IFMBE Proceedings
IFMBE Proceedings Volume 60, 2017, Pages 38-41
dc.relation.references.spa.fl_str_mv Aliot, E., Haissaguerre, M., & Jackman, W. (2008). Catheter Ablation of Atrial Fibrillation
Courtemanche, M., Ramirez, R. J., & Nattel, S. (1998). Ionic mechanisms underlying human atrial action potential properties: Insights from a mathematical model. American Journal of Physiology - Heart and Circulatory Physiology, 275(1 44-1), H301-H321.
Courtemanche, M., Ramirez, R. J., & Nattel, S. (1999). Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling: Insights from a mathematical model. Cardiovascular Research, 42(2), 477-489. doi:10.1016/S0008-6363(99)00034-6
Ficker, E., Jarolimek, W., Johann, K., Baumann, A., & Brown, A. M. (1998). Molecular determinants of dofetilide block of HERG K+ channels. Circulation Research, 82(3), 386-395.
Goralnick, E., & Bontempo, L. J. (2015). Atrial fibrillation. Emergency Medicine Clinics of North America, 33(3), 597-612. doi:10.1016/j.emc.2015.04.008
Jaiswal, A., & Goldbarg, S. (2014). Dofetilide induced torsade de pointes: Mechanism, risk factors and management strategies. Indian Heart Journal, 66(6), 640-648. doi:10.1016/j.ihj.2013.12.021
January, C. T., Wann, L. S., & Alpert, J. S. (2014). AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: Executive summary: A report of the american college of Cardiology/American heart association task force on practice guidelines and the heart rhythm society. J Am Coll Cardiol, 212.
Jurkiewicz, N. K., & Sanguinetti, M. C. (1993). Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent: Specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circulation Research, 72(1), 75-83.
Kneller, J., Zou, R., Vigmond, E. J., Wang, Z., Leon, L. J., & Nattel, S. (2002). Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties. Circulation Research, 90(9), E73-87.
Lauer, M. R. (2001). Dofetilide: Is the treatment worse than the disease? Journal of the American College of Cardiology, 37(4), 1106-1110. doi:10.1016/S0735-1097(01)01146-9
Ohler, A., Amos, G. J., Wettwer, E., & Ravens, U. (1994). Frequency-dependent effects of E-4031, almokalant, dofetilide and tedisamil on action potential duration: No evidence for "reverse use dependent" block. Naunyn-Schmiedeberg's Archives of Pharmacology, 349(6), 602-610. doi:10.1007/BF01258466
Saiz, J., Ferrero Jr., J. M., Monserrat, M., Gomis-Tena, J., Chorro, J., & Ferrero, A. (2003). Effects of the antiarrhythmic drug dofetilide on myocardial electrical activity: A computer modelling study. Paper presented at the Computers in Cardiology, 30 291-294.
Tande, P. M., Bjørnstad, H., Yang, T., & Refsum, H. (1990). Rate-dependent class III antiarrhythmic action, negative chronotropy, and positive inotropy of a novel IK blocking drug, UK-68,798: Potent in guinea pig but no effect in rat myocardium. Journal of Cardiovascular Pharmacology, 16(3), 401-410.
Van Wagoner, D. R. (2003). Electrophysiological remodeling in human atrial fibrillation. PACE - Pacing and Clinical Electrophysiology, 26(7 II), 1572-1575.
Voigt, N., Rozmaritsa, N., Trausch, A., Zimniak, T., Christ, T., Wettwer, E., . . . Ravens, U. (2010). Inhibition of IK,ACh current may contribute to clinical efficacy of class i and class III antiarrhythmic drugs in patients with atrial fibrillation. Naunyn-Schmiedeberg's Archives of Pharmacology, 381(3), 251-259. doi:10.1007/s00210-009-0452-6
Zimetbaum, P. (2012). Antiarrhythmic drug therapy for atrial fibrillation. Circulation, 125(2), 381-389. doi:10.1161/CIRCULATIONAHA.111.019927
Zipes, D. P., & Jalife, J. (1995). Cardiac Electrophysiology: From Cell to Bedside.
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_16ec
rights_invalid_str_mv http://purl.org/coar/access_right/c_16ec
dc.publisher.spa.fl_str_mv Springer Verlag
dc.publisher.faculty.spa.fl_str_mv Facultad de Ciencias Básicas
dc.source.spa.fl_str_mv Scopus
institution Universidad de Medellín
repository.name.fl_str_mv Repositorio Institucional Universidad de Medellin
repository.mail.fl_str_mv repositorio@udem.edu.co
_version_ 1814159163795701760
spelling 2017-12-19T19:36:43Z2017-12-19T19:36:43Z2017978981104085616800737http://hdl.handle.net/11407/427510.1007/978-981-10-4086-3_10reponame:Repositorio Institucional Universidad de Medellíninstname:Universidad de MedellínAtrial fibrillation is the most common sustained cardiac arrhythmia. Dofetilide is an antiarrhythmic drug for the treatment of chronic AF that specifically blocks the rapid component of the delayed rectifier potassium current IKr. Dofetilide prolongs the action potential duration and QT interval in a concentration-dependent fashion, therefore, the risk of QT prolongation is dose related. It is important to study the electrophysiological effects of dofetilide at different concentrations in human atrial cells. For this, we simulated the effects of dofetilide on human atrial cell and studied its effect on atrial action potential under normal conditions and during cAF. We developed a model of dofetilide effects on IKrand IKACh. Our results show that dofetilide blocks both currents in a fraction greater as the concentration increases, which results in an action potential duration lengthening. To our knowledge, this is the first work that has developed mathematical models of dofetilide effects on IKrand IKAChcurrents to study its effect on human atrial action potential. © Springer Nature Singapore Pte Ltd. 2017.engSpringer VerlagFacultad de Ciencias Básicashttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85018409745&doi=10.1007%2f978-981-10-4086-3_10&partnerID=40&md5=280d9472ab3c08a89e7be6b0469e002eIFMBE ProceedingsIFMBE Proceedings Volume 60, 2017, Pages 38-41Aliot, E., Haissaguerre, M., & Jackman, W. (2008). Catheter Ablation of Atrial FibrillationCourtemanche, M., Ramirez, R. J., & Nattel, S. (1998). Ionic mechanisms underlying human atrial action potential properties: Insights from a mathematical model. American Journal of Physiology - Heart and Circulatory Physiology, 275(1 44-1), H301-H321.Courtemanche, M., Ramirez, R. J., & Nattel, S. (1999). Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling: Insights from a mathematical model. Cardiovascular Research, 42(2), 477-489. doi:10.1016/S0008-6363(99)00034-6Ficker, E., Jarolimek, W., Johann, K., Baumann, A., & Brown, A. M. (1998). Molecular determinants of dofetilide block of HERG K+ channels. Circulation Research, 82(3), 386-395.Goralnick, E., & Bontempo, L. J. (2015). Atrial fibrillation. Emergency Medicine Clinics of North America, 33(3), 597-612. doi:10.1016/j.emc.2015.04.008Jaiswal, A., & Goldbarg, S. (2014). Dofetilide induced torsade de pointes: Mechanism, risk factors and management strategies. Indian Heart Journal, 66(6), 640-648. doi:10.1016/j.ihj.2013.12.021January, C. T., Wann, L. S., & Alpert, J. S. (2014). AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: Executive summary: A report of the american college of Cardiology/American heart association task force on practice guidelines and the heart rhythm society. J Am Coll Cardiol, 212.Jurkiewicz, N. K., & Sanguinetti, M. C. (1993). Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent: Specific block of rapidly activating delayed rectifier K+ current by dofetilide. Circulation Research, 72(1), 75-83.Kneller, J., Zou, R., Vigmond, E. J., Wang, Z., Leon, L. J., & Nattel, S. (2002). Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties. Circulation Research, 90(9), E73-87.Lauer, M. R. (2001). Dofetilide: Is the treatment worse than the disease? Journal of the American College of Cardiology, 37(4), 1106-1110. doi:10.1016/S0735-1097(01)01146-9Ohler, A., Amos, G. J., Wettwer, E., & Ravens, U. (1994). Frequency-dependent effects of E-4031, almokalant, dofetilide and tedisamil on action potential duration: No evidence for "reverse use dependent" block. Naunyn-Schmiedeberg's Archives of Pharmacology, 349(6), 602-610. doi:10.1007/BF01258466Saiz, J., Ferrero Jr., J. M., Monserrat, M., Gomis-Tena, J., Chorro, J., & Ferrero, A. (2003). Effects of the antiarrhythmic drug dofetilide on myocardial electrical activity: A computer modelling study. Paper presented at the Computers in Cardiology, 30 291-294.Tande, P. M., Bjørnstad, H., Yang, T., & Refsum, H. (1990). Rate-dependent class III antiarrhythmic action, negative chronotropy, and positive inotropy of a novel IK blocking drug, UK-68,798: Potent in guinea pig but no effect in rat myocardium. Journal of Cardiovascular Pharmacology, 16(3), 401-410.Van Wagoner, D. R. (2003). Electrophysiological remodeling in human atrial fibrillation. PACE - Pacing and Clinical Electrophysiology, 26(7 II), 1572-1575.Voigt, N., Rozmaritsa, N., Trausch, A., Zimniak, T., Christ, T., Wettwer, E., . . . Ravens, U. (2010). Inhibition of IK,ACh current may contribute to clinical efficacy of class i and class III antiarrhythmic drugs in patients with atrial fibrillation. Naunyn-Schmiedeberg's Archives of Pharmacology, 381(3), 251-259. doi:10.1007/s00210-009-0452-6Zimetbaum, P. (2012). Antiarrhythmic drug therapy for atrial fibrillation. Circulation, 125(2), 381-389. doi:10.1161/CIRCULATIONAHA.111.019927Zipes, D. P., & Jalife, J. (1995). Cardiac Electrophysiology: From Cell to Bedside.ScopusDofetilide effect on human atrial action potential under normal and atrial fibrillation conditions. In silico studyConference Paperinfo:eu-repo/semantics/conferenceObjecthttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_c94fTobón, C., MATBIOM, Universidad de Medellín, Medellín, ColombiaPérez, S., Grupo de Dinámica Cardiovascular, Universidad Pontificia Bolivariana, Medellín, ColombiaUgarte, J.P., Grupo de Dinámica Cardiovascular, Universidad Pontificia Bolivariana, Medellín, ColombiaSaiz, J., CI2B, Universitat Politècnica de València, Valencia, SpainTobón C.Pérez S.Ugarte J.P.Saiz J.MATBIOM, Universidad de Medellín, Medellín, ColombiaGrupo de Dinámica Cardiovascular, Universidad Pontificia Bolivariana, Medellín, ColombiaCI2B, Universitat Politècnica de València, Valencia, SpainAntiarrhythmic drugAtrial fibrillationDofetilideIn silico modelBiomedical engineeringElectric rectifiersElectrophysiologyAction potential durationsAntiarrhythmic drugAtrial fibrillationCardiac arrhythmiaConcentration-dependentDofetilideIn-silico modelsPotassium currentsDiseasesAtrial fibrillation is the most common sustained cardiac arrhythmia. Dofetilide is an antiarrhythmic drug for the treatment of chronic AF that specifically blocks the rapid component of the delayed rectifier potassium current IKr. Dofetilide prolongs the action potential duration and QT interval in a concentration-dependent fashion, therefore, the risk of QT prolongation is dose related. It is important to study the electrophysiological effects of dofetilide at different concentrations in human atrial cells. For this, we simulated the effects of dofetilide on human atrial cell and studied its effect on atrial action potential under normal conditions and during cAF. We developed a model of dofetilide effects on IKrand IKACh. Our results show that dofetilide blocks both currents in a fraction greater as the concentration increases, which results in an action potential duration lengthening. To our knowledge, this is the first work that has developed mathematical models of dofetilide effects on IKrand IKAChcurrents to study its effect on human atrial action potential. © Springer Nature Singapore Pte Ltd. 2017.http://purl.org/coar/access_right/c_16ec11407/4275oai:repository.udem.edu.co:11407/42752020-05-27 16:38:04.708Repositorio Institucional Universidad de Medellinrepositorio@udem.edu.co

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