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Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts

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Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts

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dc.contributor.author Mora-Fenoll, María Teresa es_ES
dc.contributor.author Gomez, Juan F. es_ES
dc.contributor.author Morley, Gregory es_ES
dc.contributor.author Ferrero De Loma-Osorio, José María es_ES
dc.contributor.author Trenor Gomis, Beatriz Ana es_ES
dc.date.accessioned 2020-06-16T03:45:30Z
dc.date.available 2020-06-16T03:45:30Z
dc.date.issued 2019-06-18 es_ES
dc.identifier.issn 1932-6203 es_ES
dc.identifier.uri http://hdl.handle.net/10251/146434
dc.description.abstract [EN] Heart failure (HF) is characterized, among other factors, by a progressive loss of contractile function and by the formation of an arrhythmogenic substrate, both aspects partially related to intracellular Ca2+ cycling disorders. In failing hearts both electrophysiological and structural remodeling, including fibroblast proliferation, contribute to changes in Ca2+ handling which promote the appearance of Ca2+ alternans (Ca-alt). Ca-alt in turn give rise to repolarization alternans, which promote dispersion of repolarization and contribute to reentrant activity. The computational analysis of the incidence of Ca2+ and/or repolarization alternans under HF conditions in the presence of fibroblasts could provide a better understanding of the mechanisms leading to HF arrhythmias and contractile function disorders. Methods and findings The goal of the present study was to investigate in silico the mechanisms leading to the formation of Ca-alt in failing human ventricular myocytes and tissues with disperse fibroblast distributions. The contribution of ionic currents variability to alternans formation at the cellular level was analyzed and the results show that in normal ventricular tissue, altered Ca2+ dynamics lead to Ca-alt, which precede APD alternans and can be aggravated by the presence of fibroblasts. Electrophysiological remodeling of failing tissue alone is sufficient to develop alternans. The incidence of alternans is reduced when fibroblasts are present in failing tissue due to significantly depressed Ca2+ transients. The analysis of the underlying ionic mechanisms suggests that Ca-alt are driven by Ca2+-handling protein and Ca2+ cycling dysfunctions in the junctional sarcoplasmic reticulum and that their contribution to alternans occurrence depends on the cardiac remodeling conditions and on myocyte-fibroblast interactions. Conclusion It can thus be concluded that fibroblasts modulate the formation of Ca-alt in human ventricular tissue subjected to heart failure-related electrophysiological remodeling. Pharmacological therapies should thus consider the extent of both the electrophysiological and structural remodeling present in the failing heart. es_ES
dc.description.sponsorship This work was partially supported by the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013 2016" from the Ministerio de Economía, Industria y Competitividad of Spain and Fondo Europeo de Desarrollo Regional (FEDER) DPI2016-75799-R (AEI/FEDER, UE), and by the Programa de Ayudas de Investigación y Desarrollo (PAID-01-17) from the Universitat Politècnica de València. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. es_ES
dc.language Inglés es_ES
dc.publisher Public Library of Science es_ES
dc.relation.ispartof PLoS ONE es_ES
dc.rights Reconocimiento (by) es_ES
dc.subject Sarcoplasmic-Reticulum Ca2+ es_ES
dc.subject Action-Potential dynamics es_ES
dc.subject Electrical alternans es_ES
dc.subject Cardiac alternans es_ES
dc.subject Ventricular myocytes es_ES
dc.subject Cellular alternans es_ES
dc.subject Conduction es_ES
dc.subject Model es_ES
dc.subject Repolarization es_ES
dc.subject Tissue es_ES
dc.subject.classification TECNOLOGIA ELECTRONICA es_ES
dc.title Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.1371/journal.pone.0217993 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/UPV//PAID-01-17/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/MINECO//DPI2016-75799-R/ES/TECNOLOGIAS COMPUTACIONALES PARA LA OPTIMIZACION DE TERAPIAS PERSONALIZADAS DE PATOLOGIAS AURICULARES Y VENTRICULARES/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Electrónica - Departament d'Enginyeria Electrònica es_ES
dc.description.bibliographicCitation Mora-Fenoll, MT.; Gomez, JF.; Morley, G.; Ferrero De Loma-Osorio, JM.; Trenor Gomis, BA. (2019). Mechanistic investigation of Ca2+ alternans in human heart failure and its modulation by fibroblasts. PLoS ONE. 14(6):1-19. https://doi.org/10.1371/journal.pone.0217993 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.1371/journal.pone.0217993 es_ES
dc.description.upvformatpinicio 1 es_ES
dc.description.upvformatpfin 19 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 14 es_ES
dc.description.issue 6 es_ES
dc.identifier.pmid 31211790 es_ES
dc.identifier.pmcid PMC6581251 es_ES
dc.relation.pasarela S\392023 es_ES
dc.contributor.funder Universitat Politècnica de València es_ES
dc.contributor.funder Ministerio de Economía y Competitividad es_ES
dc.description.references Glukhov, A. V., Fedorov, V. V., Kalish, P. W., Ravikumar, V. K., Lou, Q., Janks, D., … Efimov, I. R. (2012). Conduction Remodeling in Human End-Stage Nonischemic Left Ventricular Cardiomyopathy. Circulation, 125(15), 1835-1847. doi:10.1161/circulationaha.111.047274 es_ES
dc.description.references Lou, Q., Fedorov, V. V., Glukhov, A. V., Moazami, N., Fast, V. G., & Efimov, I. R. (2011). Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure. Circulation, 123(17), 1881-1890. doi:10.1161/circulationaha.110.989707 es_ES
dc.description.references Gomez, J. F., Cardona, K., & Trenor, B. (2015). Lessons learned from multi-scale modeling of the failing heart. Journal of Molecular and Cellular Cardiology, 89, 146-159. doi:10.1016/j.yjmcc.2015.10.016 es_ES
dc.description.references Kohl, P., & Gourdie, R. G. (2014). Fibroblast–myocyte electrotonic coupling: Does it occur in native cardiac tissue? Journal of Molecular and Cellular Cardiology, 70, 37-46. doi:10.1016/j.yjmcc.2013.12.024 es_ES
dc.description.references Gaudesius, G., Miragoli, M., Thomas, S. P., & Rohr, S. (2003). Coupling of Cardiac Electrical Activity Over Extended Distances by Fibroblasts of Cardiac Origin. Circulation Research, 93(5), 421-428. doi:10.1161/01.res.0000089258.40661.0c es_ES
dc.description.references Kohl, P., Camelliti, P., Burton, F. L., & Smith, G. L. (2005). Electrical coupling of fibroblasts and myocytes: relevance for cardiac propagation. Journal of Electrocardiology, 38(4), 45-50. doi:10.1016/j.jelectrocard.2005.06.096 es_ES
dc.description.references Camelliti, P., Green, C. R., LeGrice, I., & Kohl, P. (2004). Fibroblast Network in Rabbit Sinoatrial Node. Circulation Research, 94(6), 828-835. doi:10.1161/01.res.0000122382.19400.14 es_ES
dc.description.references Rook, M. B., van Ginneken, A. C., de Jonge, B., el Aoumari, A., Gros, D., & Jongsma, H. J. (1992). Differences in gap junction channels between cardiac myocytes, fibroblasts, and heterologous pairs. American Journal of Physiology-Cell Physiology, 263(5), C959-C977. doi:10.1152/ajpcell.1992.263.5.c959 es_ES
dc.description.references Mahoney, V. M., Mezzano, V., Mirams, G. R., Maass, K., Li, Z., Cerrone, M., … Morley, G. E. (2016). Connexin43 contributes to electrotonic conduction across scar tissue in the intact heart. Scientific Reports, 6(1). doi:10.1038/srep26744 es_ES
dc.description.references Quinn, T. A., Camelliti, P., Rog-Zielinska, E. A., Siedlecka, U., Poggioli, T., O’Toole, E. T., … Kohl, P. (2016). Electrotonic coupling of excitable and nonexcitable cells in the heart revealed by optogenetics. Proceedings of the National Academy of Sciences, 113(51), 14852-14857. doi:10.1073/pnas.1611184114 es_ES
dc.description.references Rubart, M., Tao, W., Lu, X.-L., Conway, S. J., Reuter, S. P., Lin, S.-F., & Soonpaa, M. H. (2017). Electrical coupling between ventricular myocytes and myofibroblasts in the infarcted mouse heart. Cardiovascular Research, 114(3), 389-400. doi:10.1093/cvr/cvx163 es_ES
dc.description.references Miragoli, M., Gaudesius, G., & Rohr, S. (2006). Electrotonic Modulation of Cardiac Impulse Conduction by Myofibroblasts. Circulation Research, 98(6), 801-810. doi:10.1161/01.res.0000214537.44195.a3 es_ES
dc.description.references Jacquemet, V., & Henriquez, C. S. (2008). Loading effect of fibroblast-myocyte coupling on resting potential, impulse propagation, and repolarization: insights from a microstructure model. American Journal of Physiology-Heart and Circulatory Physiology, 294(5), H2040-H2052. doi:10.1152/ajpheart.01298.2007 es_ES
dc.description.references Li, Y., Asfour, H., & Bursac, N. (2017). Age-dependent functional crosstalk between cardiac fibroblasts and cardiomyocytes in a 3D engineered cardiac tissue. Acta Biomaterialia, 55, 120-130. doi:10.1016/j.actbio.2017.04.027 es_ES
dc.description.references Zlochiver, S., Muñoz, V., Vikstrom, K. L., Taffet, S. M., Berenfeld, O., & Jalife, J. (2008). Electrotonic Myofibroblast-to-Myocyte Coupling Increases Propensity to Reentrant Arrhythmias in Two-Dimensional Cardiac Monolayers. Biophysical Journal, 95(9), 4469-4480. doi:10.1529/biophysj.108.136473 es_ES
dc.description.references Nguyen, T. P., Xie, Y., Garfinkel, A., Qu, Z., & Weiss, J. N. (2011). Arrhythmogenic consequences of myofibroblast–myocyte coupling. Cardiovascular Research, 93(2), 242-251. doi:10.1093/cvr/cvr292 es_ES
dc.description.references Greisas, A., & Zlochiver, S. (2016). The Multi-Domain Fibroblast/Myocyte Coupling in the Cardiac Tissue: A Theoretical Study. Cardiovascular Engineering and Technology, 7(3), 290-304. doi:10.1007/s13239-016-0266-x es_ES
dc.description.references Sridhar, S., Vandersickel, N., & Panfilov, A. V. (2017). Effect of myocyte-fibroblast coupling on the onset of pathological dynamics in a model of ventricular tissue. Scientific Reports, 7(1). doi:10.1038/srep40985 es_ES
dc.description.references Gomez, J. F., Cardona, K., Martinez, L., Saiz, J., & Trenor, B. (2014). Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 2D Simulation Study. PLoS ONE, 9(7), e103273. doi:10.1371/journal.pone.0103273 es_ES
dc.description.references KODAMA, M., KATO, K., HIRONO, S., OKURA, Y., HANAWA, H., YOSHIDA, T., … AIZAWA, Y. (2004). Linkage Between Mechanical and Electrical Alternans in Patients with Chronic Heart Failure. Journal of Cardiovascular Electrophysiology, 15(3), 295-299. doi:10.1046/j.1540-8167.2004.03016.x es_ES
dc.description.references Rosenbaum, D. S., Jackson, L. E., Smith, J. M., Garan, H., Ruskin, J. N., & Cohen, R. J. (1994). Electrical Alternans and Vulnerability to Ventricular Arrhythmias. New England Journal of Medicine, 330(4), 235-241. doi:10.1056/nejm199401273300402 es_ES
dc.description.references Jordan, P. N., & Christini, D. J. (2006). Action Potential Morphology Influences Intracellular Calcium Handling Stability and the Occurrence of Alternans. Biophysical Journal, 90(2), 672-680. doi:10.1529/biophysj.105.071340 es_ES
dc.description.references Cherry, E. M. (2017). Distinguishing mechanisms for alternans in cardiac cells using constant-diastolic-interval pacing. Chaos: An Interdisciplinary Journal of Nonlinear Science, 27(9), 093902. doi:10.1063/1.4999354 es_ES
dc.description.references Groenendaal, W., Ortega, F. A., Krogh-Madsen, T., & Christini, D. J. (2014). Voltage and Calcium Dynamics Both Underlie Cellular Alternans in Cardiac Myocytes. Biophysical Journal, 106(10), 2222-2232. doi:10.1016/j.bpj.2014.03.048 es_ES
dc.description.references Nolasco, J. B., & Dahlen, R. W. (1968). A graphic method for the study of alternation in cardiac action potentials. Journal of Applied Physiology, 25(2), 191-196. doi:10.1152/jappl.1968.25.2.191 es_ES
dc.description.references Picht, E., DeSantiago, J., Blatter, L. A., & Bers, D. M. (2006). Cardiac Alternans Do Not Rely on Diastolic Sarcoplasmic Reticulum Calcium Content Fluctuations. Circulation Research, 99(7), 740-748. doi:10.1161/01.res.0000244002.88813.91 es_ES
dc.description.references Díaz, M. E., O’Neill, S. C., & Eisner, D. A. (2004). Sarcoplasmic Reticulum Calcium Content Fluctuation Is the Key to Cardiac Alternans. Circulation Research, 94(5), 650-656. doi:10.1161/01.res.0000119923.64774.72 es_ES
dc.description.references Zhou, X., Bueno-Orovio, A., Orini, M., Hanson, B., Hayward, M., Taggart, P., … Rodriguez, B. (2016). In Vivo and In Silico Investigation Into Mechanisms of Frequency Dependence of Repolarization Alternans in Human Ventricular Cardiomyocytes. Circulation Research, 118(2), 266-278. doi:10.1161/circresaha.115.307836 es_ES
dc.description.references Xie, L.-H., Sato, D., Garfinkel, A., Qu, Z., & Weiss, J. N. (2008). Intracellular Ca Alternans: Coordinated Regulation by Sarcoplasmic Reticulum Release, Uptake, and Leak. Biophysical Journal, 95(6), 3100-3110. doi:10.1529/biophysj.108.130955 es_ES
dc.description.references Cutler, M. J., Wan, X., Laurita, K. R., Hajjar, R. J., & Rosenbaum, D. S. (2009). Targeted SERCA2a Gene Expression Identifies Molecular Mechanism and Therapeutic Target for Arrhythmogenic Cardiac Alternans. Circulation: Arrhythmia and Electrophysiology, 2(6), 686-694. doi:10.1161/circep.109.863118 es_ES
dc.description.references Kanaporis, G., & Blatter, L. A. (2015). The Mechanisms of Calcium Cycling and Action Potential Dynamics in Cardiac Alternans. Circulation Research, 116(5), 846-856. doi:10.1161/circresaha.116.305404 es_ES
dc.description.references Pastore, J. M., Girouard, S. D., Laurita, K. R., Akar, F. G., & Rosenbaum, D. S. (1999). Mechanism Linking T-Wave Alternans to the Genesis of Cardiac Fibrillation. Circulation, 99(10), 1385-1394. doi:10.1161/01.cir.99.10.1385 es_ES
dc.description.references O’Hara, T., Virág, L., Varró, A., & Rudy, Y. (2011). Simulation of the Undiseased Human Cardiac Ventricular Action Potential: Model Formulation and Experimental Validation. PLoS Computational Biology, 7(5), e1002061. doi:10.1371/journal.pcbi.1002061 es_ES
dc.description.references Mora, M. T., Ferrero, J. M., Romero, L., & Trenor, B. (2017). Sensitivity analysis revealing the effect of modulating ionic mechanisms on calcium dynamics in simulated human heart failure. PLOS ONE, 12(11), e0187739. doi:10.1371/journal.pone.0187739 es_ES
dc.description.references Andrew MacCannell, K., Bazzazi, H., Chilton, L., Shibukawa, Y., Clark, R. B., & Giles, W. R. (2007). A Mathematical Model of Electrotonic Interactions between Ventricular Myocytes and Fibroblasts. Biophysical Journal, 92(11), 4121-4132. doi:10.1529/biophysj.106.101410 es_ES
dc.description.references Spach, M. S., Heidlage, J. F., Dolber, P. C., & Barr, R. C. (2000). Electrophysiological Effects of Remodeling Cardiac Gap Junctions and Cell Size. Circulation Research, 86(3), 302-311. doi:10.1161/01.res.86.3.302 es_ES
dc.description.references Kieval, R. S., Spear, J. F., & Moore, E. N. (1992). Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium. Circulation Research, 71(1), 127-136. doi:10.1161/01.res.71.1.127 es_ES
dc.description.references Gomez, J. F., Cardona, K., Romero, L., Ferrero, J. M., & Trenor, B. (2014). Electrophysiological and Structural Remodeling in Heart Failure Modulate Arrhythmogenesis. 1D Simulation Study. PLoS ONE, 9(9), e106602. doi:10.1371/journal.pone.0106602 es_ES
dc.description.references Taggart, P., Sutton, P. M., Opthof, T., Coronel, R., Trimlett, R., Pugsley, W., & Kallis, P. (2000). Inhomogeneous Transmural Conduction During Early Ischaemia in Patients with Coronary Artery Disease. Journal of Molecular and Cellular Cardiology, 32(4), 621-630. doi:10.1006/jmcc.2000.1105 es_ES
dc.description.references Heidenreich E. Algoritmos para ecuaciones de reacción difusión aplicados a electrofisiología. Ph.D. Thesis. Universidad de Zaragoza. 2009. https://institutoi4.net/wp-content/uploads/2017/08/TesisEAH.pdf es_ES
dc.description.references Heidenreich, E. A., Ferrero, J. M., Doblaré, M., & Rodríguez, J. F. (2010). Adaptive Macro Finite Elements for the Numerical Solution of Monodomain Equations in Cardiac Electrophysiology. Annals of Biomedical Engineering, 38(7), 2331-2345. doi:10.1007/s10439-010-9997-2 es_ES
dc.description.references Xie, Y., Garfinkel, A., Weiss, J. N., & Qu, Z. (2009). Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models. American Journal of Physiology-Heart and Circulatory Physiology, 297(2), H775-H784. doi:10.1152/ajpheart.00341.2009 es_ES
dc.description.references Luo, C. H., & Rudy, Y. (1991). A model of the ventricular cardiac action potential. Depolarization, repolarization, and their interaction. Circulation Research, 68(6), 1501-1526. doi:10.1161/01.res.68.6.1501 es_ES
dc.description.references Pruvot, E. J., Katra, R. P., Rosenbaum, D. S., & Laurita, K. R. (2004). Role of Calcium Cycling Versus Restitution in the Mechanism of Repolarization Alternans. Circulation Research, 94(8), 1083-1090. doi:10.1161/01.res.0000125629.72053.95 es_ES
dc.description.references Kanaporis, G., & Blatter, L. A. (2017). Membrane potential determines calcium alternans through modulation of SR Ca 2+ load and L-type Ca 2+ current. Journal of Molecular and Cellular Cardiology, 105, 49-58. doi:10.1016/j.yjmcc.2017.02.004 es_ES
dc.description.references Goldhaber, J. I., Xie, L.-H., Duong, T., Motter, C., Khuu, K., & Weiss, J. N. (2005). Action Potential Duration Restitution and Alternans in Rabbit Ventricular Myocytes. Circulation Research, 96(4), 459-466. doi:10.1161/01.res.0000156891.66893.83 es_ES
dc.description.references Walmsley, J., Rodriguez, J. F., Mirams, G. R., Burrage, K., Efimov, I. R., & Rodriguez, B. (2013). mRNA Expression Levels in Failing Human Hearts Predict Cellular Electrophysiological Remodeling: A Population-Based Simulation Study. PLoS ONE, 8(2), e56359. doi:10.1371/journal.pone.0056359 es_ES
dc.description.references Narayan, S. M., Bayer, J. D., Lalani, G., & Trayanova, N. A. (2008). Action Potential Dynamics Explain Arrhythmic Vulnerability in Human Heart Failure. Journal of the American College of Cardiology, 52(22), 1782-1792. doi:10.1016/j.jacc.2008.08.037 es_ES
dc.description.references Livshitz, L. M., & Rudy, Y. (2007). Regulation of Ca2+ and electrical alternans in cardiac myocytes: role of CAMKII and repolarizing currents. American Journal of Physiology-Heart and Circulatory Physiology, 292(6), H2854-H2866. doi:10.1152/ajpheart.01347.2006 es_ES
dc.description.references WILSON, L. D., WAN, X., & ROSENBAUM, D. S. (2006). Cellular Alternans: A Mechanism Linking Calcium Cycling Proteins to Cardiac Arrhythmogenesis. Annals of the New York Academy of Sciences, 1080(1), 216-234. doi:10.1196/annals.1380.018 es_ES
dc.description.references Wilson, L. D., Jeyaraj, D., Wan, X., Hoeker, G. S., Said, T. H., Gittinger, M., … Rosenbaum, D. S. (2009). Heart failure enhances susceptibility to arrhythmogenic cardiac alternans. Heart Rhythm, 6(2), 251-259. doi:10.1016/j.hrthm.2008.11.008 es_ES
dc.description.references Cutler, M. J., Wan, X., Plummer, B. N., Liu, H., Deschenes, I., Laurita, K. R., … Rosenbaum, D. S. (2012). Targeted Sarcoplasmic Reticulum Ca 2+ ATPase 2a Gene Delivery to Restore Electrical Stability in the Failing Heart. Circulation, 126(17), 2095-2104. doi:10.1161/circulationaha.111.071480 es_ES
dc.description.references Bayer, J. D., Narayan, S. M., Lalani, G. G., & Trayanova, N. A. (2010). Rate-dependent action potential alternans in human heart failure implicates abnormal intracellular calcium handling. Heart Rhythm, 7(8), 1093-1101. doi:10.1016/j.hrthm.2010.04.008 es_ES
dc.description.references Wang, L., Myles, R. C., De Jesus, N. M., Ohlendorf, A. K. P., Bers, D. M., & Ripplinger, C. M. (2014). Optical Mapping of Sarcoplasmic Reticulum Ca 2+ in the Intact Heart. Circulation Research, 114(9), 1410-1421. doi:10.1161/circresaha.114.302505 es_ES
dc.description.references Rovetti, R., Cui, X., Garfinkel, A., Weiss, J. N., & Qu, Z. (2010). Spark-Induced Sparks As a Mechanism of Intracellular Calcium Alternans in Cardiac Myocytes. Circulation Research, 106(10), 1582-1591. doi:10.1161/circresaha.109.213975 es_ES
dc.description.references Tomek, J., Tomková, M., Zhou, X., Bub, G., & Rodriguez, B. (2018). Modulation of Cardiac Alternans by Altered Sarcoplasmic Reticulum Calcium Release: A Simulation Study. Frontiers in Physiology, 9. doi:10.3389/fphys.2018.01306 es_ES
dc.description.references Hammer, K. P., Ljubojevic, S., Ripplinger, C. M., Pieske, B. M., & Bers, D. M. (2015). Cardiac myocyte alternans in intact heart: Influence of cell–cell coupling and β-adrenergic stimulation. Journal of Molecular and Cellular Cardiology, 84, 1-9. doi:10.1016/j.yjmcc.2015.03.012 es_ES
dc.description.references Majumder, R., Engels, M. C., de Vries, A. A. F., Panfilov, A. V., & Pijnappels, D. A. (2016). Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium. Scientific Reports, 6(1). doi:10.1038/srep24334 es_ES
dc.description.references Shiferaw, Y., & Karma, A. (2006). Turing instability mediated by voltage and calcium diffusion in paced cardiac cells. Proceedings of the National Academy of Sciences, 103(15), 5670-5675. doi:10.1073/pnas.0511061103 es_ES
dc.description.references Sato, D., Shiferaw, Y., Garfinkel, A., Weiss, J. N., Qu, Z., & Karma, A. (2006). Spatially Discordant Alternans in Cardiac Tissue. Circulation Research, 99(5), 520-527. doi:10.1161/01.res.0000240542.03986.e7 es_ES


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