Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study
The rotor ablation has gained favor in recent years to treat chronic atrial fibrillation (CAF). However, it may cause complications in patients and the results remain suboptimal. Besides, antiarrhythmic drugs for the management of AF are not sufficiently effective and can cause significant cardiac a...
- Autores:
- Tipo de recurso:
- Fecha de publicación:
- 2018
- Institución:
- Universidad de Medellín
- Repositorio:
- Repositorio UDEM
- Idioma:
- eng
- OAI Identifier:
- oai:repository.udem.edu.co:11407/5719
- Acceso en línea:
- http://hdl.handle.net/11407/5719
- Palabra clave:
- Cardiology
Drug interactions
Modulation
Antiarrhythmic drug
Atrial fibrillation
Atrial tissues
Computational model
Hill's equation
Non-localized
Rotor modulation
Specific distribution
Room and pillar mining
- Rights
- License
- http://purl.org/coar/access_right/c_16ec
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Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study |
| title |
Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study |
| spellingShingle |
Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study Cardiology Drug interactions Modulation Antiarrhythmic drug Atrial fibrillation Atrial tissues Computational model Hill's equation Non-localized Rotor modulation Specific distribution Room and pillar mining |
| title_short |
Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study |
| title_full |
Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study |
| title_fullStr |
Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study |
| title_full_unstemmed |
Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study |
| title_sort |
Atrial Rotor Modulation by Localized Dofetilide Application: An in Silico Study |
| dc.subject.none.fl_str_mv |
Cardiology Drug interactions Modulation Antiarrhythmic drug Atrial fibrillation Atrial tissues Computational model Hill's equation Non-localized Rotor modulation Specific distribution Room and pillar mining |
| topic |
Cardiology Drug interactions Modulation Antiarrhythmic drug Atrial fibrillation Atrial tissues Computational model Hill's equation Non-localized Rotor modulation Specific distribution Room and pillar mining |
| description |
The rotor ablation has gained favor in recent years to treat chronic atrial fibrillation (CAF). However, it may cause complications in patients and the results remain suboptimal. Besides, antiarrhythmic drugs for the management of AF are not sufficiently effective and can cause significant cardiac and extracardiac side effects. To reduce the risk and increase the effectiveness, a rotor modulation via the localized release of dofetilide is proposed through an in silico study. A computational model of two-dimensional atrial tissue was implemented using human cell model under CAF conditions. Dofetilide was modeled blocking the ionic currents IKr and IKACH using Hill's equation. A CAF episode, sustained by a rotor, was simulated. Different concentrations of dofetilide were applied in specific distributions based on the rotor tip location, detected by phase map analysis. Non-localized application of dofetilide resulted in the benefit of CAF progression. In contrast, localized dofetilide liberation terminated the CAF episode. These results could have therapeutic implications in novel treatments of CAF. © 2018 Creative Commons Attribution. |
| publishDate |
2018 |
| dc.date.accessioned.none.fl_str_mv |
2020-04-29T14:53:46Z |
| dc.date.available.none.fl_str_mv |
2020-04-29T14:53:46Z |
| dc.date.none.fl_str_mv |
2018 |
| dc.type.eng.fl_str_mv |
Conference Paper |
| dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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http://purl.org/coar/resource_type/c_2df8fbb1 |
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info:eu-repo/semantics/article |
| dc.identifier.isbn.none.fl_str_mv |
9781728109589 |
| dc.identifier.issn.none.fl_str_mv |
23258861 |
| dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/11407/5719 |
| dc.identifier.doi.none.fl_str_mv |
10.22489/CinC.2018.359 |
| identifier_str_mv |
9781728109589 23258861 10.22489/CinC.2018.359 |
| url |
http://hdl.handle.net/11407/5719 |
| dc.language.iso.none.fl_str_mv |
eng |
| language |
eng |
| dc.relation.isversionof.none.fl_str_mv |
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068790406&doi=10.22489%2fCinC.2018.359&partnerID=40&md5=3dcc390ee631638e8d87e8e20a2b1592 |
| dc.relation.citationvolume.none.fl_str_mv |
2018-September |
| dc.relation.references.none.fl_str_mv |
Lau, D.H., Linz, D., Schotten, U., Mahajan, R., Sanders, P., Kalman, J.M., Pathophysiology of paroxysmal and persistent atrial fibrillation: Rotors, foci and fibrosis (2017) Hear. Lung Circ, 9506 (17), pp. 1-7 Krummen, D.E., Swarup, V., Narayan, S.M., The role of rotors in atrial fibrillation (2015) J. Thorac. Dis, 7 (2), pp. 142-151. , Feb Parameswaran, R., Voskoboinik, A., Gorelik, A., Lee, G., Kistler, P.M., Sanders, P., Kalman, J.M., Clinical impact of rotor ablation in atrial fibrillation: A systematic review (2018) EP Eur, 20 (7), pp. 1099-1106. , Jul Ravens, U., Odening, K.E., Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers (2017) Pharmacol. Ther, 176, pp. 13-21. , Aug Tobón, C., Pérez, S., Ugarte, J.P., Saiz, J., Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions (2016) Silico Study BT-VII Latin American Congress on Biomedical Engineering CLAIB 2016, 2017, pp. 38-41. , Bucaramanga, Santander, Colombia, October 26th-28th Courtemanche, M., Ramirez, R.J., Nattel, S., Ionic mechanisms underlying human atrial action potential properties: Insights from a mathematical model (1998) Am. J. Physiol, 275 (1), pp. H301-H321. , Jul Courtemanche, M., Ramirez, R.J., Nattel, S., Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling: Insights from a mathematical model (1999) Cardiovasc. Res, 42 (2), pp. 477-489. , May Van Wagoner, D.R., Electrophysiological remodeling in human atrial fibrillation (2003) Pacing Clin. Electrophysiol, 26 (7), pp. 1572-1575 Ficker, E., Jarolimek, W., Kiehn, J., Baumann, A., Brown, A.M., (2015) Molecular Determinants of Dofetilide Block of HERG K Channels, pp. 386-395 Voigt, N., Rozmaritsa, N., Trausch, A., Zimniak, T., Christ, T., Wettwer, E., Matschke, K., Ravens, U., Inhibition of IK,ACh current may contribute to clinical efficacy of class i and class III antiarrhythmic drugs in patients with atrial fibrillation (2010) Naunyn. Schmiedebergs. Arch. Pharmacol, 381 (3), pp. 251-259 Bueno-Orovio, A., Kay, D., Burrage, K., Fourier spectral methods for fractional-in-space reaction-diffusion equations (2014) BIT Numer. Math, 54 (4), pp. 937-954 Berenfeld, O., The major role of IK1 in mechanisms of rotor drift in the atria : A computational study (2016) Clin. Med. Insights Cardiol, 10, pp. 71-79 Ugarte, J.P., Tobón, C., Orozco-Duque, A., Becerra, M.A., Bustamante, J., Effect of the electrograms density in detecting and ablating the tip of the rotor during chronic atrial fibrillation: An in silico study (2015) Europace, 17, pp. ii97-ii104 Guillem, M., Climent, A.M., Rodrigo, M., Fernandez-Aviles, F., Atienza, F., Berenfeld, O., Presence and stability of rotors in atrial fibrillation: Evidence and therapeutic implications (2016) Cardiovasc. Res, 109 (4), pp. 480-492 Singh, S., Zoble, R.G., Yellen, L., Brodsky, M.A., Feld, G.K., Berk, M., Billing, C.B., Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: The symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study (2000) Circulation, 102 (19), pp. 2385-2390 Allen, M.J., Nichols, D.J., Oliver, S.D., The pharmacokinetics and pharmacodynamics of oral dofetilide after twice daily and three times daily dosing (2000) Clin. Pharmacol, 50, pp. 247-253 Jaiswal, A., Goldbarg, S., Dofetilide induced torsade de pointes: Mechanism, risk factors and management strategies (2014) Indian Heart J, 66 (6), pp. 640-648 |
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http://purl.org/coar/access_right/c_16ec |
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http://purl.org/coar/access_right/c_16ec |
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IEEE Computer Society |
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Facultad de Ciencias Básicas |
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Facultad de Ciencias Básicas |
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IEEE Computer Society |
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Computing in Cardiology |
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Universidad de Medellín |
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Repositorio Institucional Universidad de Medellin |
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repositorio@udem.edu.co |
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1814159219518078976 |
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20182020-04-29T14:53:46Z2020-04-29T14:53:46Z978172810958923258861http://hdl.handle.net/11407/571910.22489/CinC.2018.359The rotor ablation has gained favor in recent years to treat chronic atrial fibrillation (CAF). However, it may cause complications in patients and the results remain suboptimal. Besides, antiarrhythmic drugs for the management of AF are not sufficiently effective and can cause significant cardiac and extracardiac side effects. To reduce the risk and increase the effectiveness, a rotor modulation via the localized release of dofetilide is proposed through an in silico study. A computational model of two-dimensional atrial tissue was implemented using human cell model under CAF conditions. Dofetilide was modeled blocking the ionic currents IKr and IKACH using Hill's equation. A CAF episode, sustained by a rotor, was simulated. Different concentrations of dofetilide were applied in specific distributions based on the rotor tip location, detected by phase map analysis. Non-localized application of dofetilide resulted in the benefit of CAF progression. In contrast, localized dofetilide liberation terminated the CAF episode. These results could have therapeutic implications in novel treatments of CAF. © 2018 Creative Commons Attribution.engIEEE Computer SocietyFacultad de Ciencias BásicasFacultad de Ciencias Básicashttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85068790406&doi=10.22489%2fCinC.2018.359&partnerID=40&md5=3dcc390ee631638e8d87e8e20a2b15922018-SeptemberLau, D.H., Linz, D., Schotten, U., Mahajan, R., Sanders, P., Kalman, J.M., Pathophysiology of paroxysmal and persistent atrial fibrillation: Rotors, foci and fibrosis (2017) Hear. Lung Circ, 9506 (17), pp. 1-7Krummen, D.E., Swarup, V., Narayan, S.M., The role of rotors in atrial fibrillation (2015) J. Thorac. Dis, 7 (2), pp. 142-151. , FebParameswaran, R., Voskoboinik, A., Gorelik, A., Lee, G., Kistler, P.M., Sanders, P., Kalman, J.M., Clinical impact of rotor ablation in atrial fibrillation: A systematic review (2018) EP Eur, 20 (7), pp. 1099-1106. , JulRavens, U., Odening, K.E., Atrial fibrillation: Therapeutic potential of atrial K+ channel blockers (2017) Pharmacol. Ther, 176, pp. 13-21. , AugTobón, C., Pérez, S., Ugarte, J.P., Saiz, J., Dofetilide effect on human atrial action potential under normal and atrial fibrillation conditions (2016) Silico Study BT-VII Latin American Congress on Biomedical Engineering CLAIB 2016, 2017, pp. 38-41. , Bucaramanga, Santander, Colombia, October 26th-28thCourtemanche, M., Ramirez, R.J., Nattel, S., Ionic mechanisms underlying human atrial action potential properties: Insights from a mathematical model (1998) Am. J. Physiol, 275 (1), pp. H301-H321. , JulCourtemanche, M., Ramirez, R.J., Nattel, S., Ionic targets for drug therapy and atrial fibrillation-induced electrical remodeling: Insights from a mathematical model (1999) Cardiovasc. Res, 42 (2), pp. 477-489. , MayVan Wagoner, D.R., Electrophysiological remodeling in human atrial fibrillation (2003) Pacing Clin. Electrophysiol, 26 (7), pp. 1572-1575Ficker, E., Jarolimek, W., Kiehn, J., Baumann, A., Brown, A.M., (2015) Molecular Determinants of Dofetilide Block of HERG K Channels, pp. 386-395Voigt, N., Rozmaritsa, N., Trausch, A., Zimniak, T., Christ, T., Wettwer, E., Matschke, K., Ravens, U., Inhibition of IK,ACh current may contribute to clinical efficacy of class i and class III antiarrhythmic drugs in patients with atrial fibrillation (2010) Naunyn. Schmiedebergs. Arch. Pharmacol, 381 (3), pp. 251-259Bueno-Orovio, A., Kay, D., Burrage, K., Fourier spectral methods for fractional-in-space reaction-diffusion equations (2014) BIT Numer. Math, 54 (4), pp. 937-954Berenfeld, O., The major role of IK1 in mechanisms of rotor drift in the atria : A computational study (2016) Clin. Med. Insights Cardiol, 10, pp. 71-79Ugarte, J.P., Tobón, C., Orozco-Duque, A., Becerra, M.A., Bustamante, J., Effect of the electrograms density in detecting and ablating the tip of the rotor during chronic atrial fibrillation: An in silico study (2015) Europace, 17, pp. ii97-ii104Guillem, M., Climent, A.M., Rodrigo, M., Fernandez-Aviles, F., Atienza, F., Berenfeld, O., Presence and stability of rotors in atrial fibrillation: Evidence and therapeutic implications (2016) Cardiovasc. Res, 109 (4), pp. 480-492Singh, S., Zoble, R.G., Yellen, L., Brodsky, M.A., Feld, G.K., Berk, M., Billing, C.B., Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: The symptomatic atrial fibrillation investigative research on dofetilide (SAFIRE-D) study (2000) Circulation, 102 (19), pp. 2385-2390Allen, M.J., Nichols, D.J., Oliver, S.D., The pharmacokinetics and pharmacodynamics of oral dofetilide after twice daily and three times daily dosing (2000) Clin. Pharmacol, 50, pp. 247-253Jaiswal, A., Goldbarg, S., Dofetilide induced torsade de pointes: Mechanism, risk factors and management strategies (2014) Indian Heart J, 66 (6), pp. 640-648Computing in CardiologyCardiologyDrug interactionsModulationAntiarrhythmic drugAtrial fibrillationAtrial tissuesComputational modelHill's equationNon-localizedRotor modulationSpecific distributionRoom and pillar miningAtrial Rotor Modulation by Localized Dofetilide Application: An in Silico StudyConference Paperinfo:eu-repo/semantics/articlehttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_2df8fbb1Perez-Buitrago, S., GI2B, Instituto Tecnológico Metropolitano, Calle 73 No. 76A - 354, Medellìn, 050034, Colombia; Ugarte, J.P., GIMSC, Universidad de San Buenaventura, Medellín, Colombia; Tobon, C., MATBIOM, Universidad de Medellín, Medellín, Colombiahttp://purl.org/coar/access_right/c_16ecPerez-Buitrago S.Ugarte J.P.Tobon C.11407/5719oai:repository.udem.edu.co:11407/57192020-05-27 18:30:56.347Repositorio Institucional Universidad de Medellinrepositorio@udem.edu.co |