Prof Arun Holden

BA, Oxford; PhD 1971, Alberta.
Emeritus Professor of Computational Biology
School of Biomedical Sciences

Background: BA (Oxford, UK); PhD (Alberta, Canada) has been at Leeds since 1971, and retired in 2012. He continues to supervise undergraduate project, and postgraduate research students in applications of computational electrophysiology to cardiac and uterine physiology, and in the analysis of clinical electrophysiological recordings and magnetic resonance imaging data. Current research is mostly focused on ante-natal and adult cardiac arrhythmia.

Contact: Garstang 7.60, +44(0) 113 34 34251, email address for  

You can read more about Prof Holden's interests here:
https://www.ncbi.nlm.nih.gov/pubmed/?term=holden+AV

Research Interests

Computational Biology

(a) The Computational Biology laboratory constructs detailed computer models of muscular organs - the beating heart, and the pregnant uterus - that are based on data from membrane, cell and tissue experiments, and from clinical data. These models are validated by their prediction of normal organ behaviour, and abnormal behaviours seen in disease. They are applied to dissect, in space and time, physiological and pathological mechanism, to prescreen drugs, and to contribute to the drug design and discovery process, and the design of physical interventions.

(b) Most of our research has been in the construction of cardiac virtual tissues, and these are now being applied to biomedical problems. Application areas include the normal pacemaking of the heart and its pharmacological control; the genetic engineering of pacemaking activity in the ventricles, as an alternative to implanted electronic pacemakers; the initiation and control of re-entrant arrhythmias in the atria and ventricles; the effects of drugs on propagation phenomena within the heart; and the effects of electrical and very large magnetic fields on the behaviour of the in situ heart. The same methodology, of developing and applying virtual tissues, is being applied to model uterine activity and possible mechanisms in premature and normal labour.

(c) An important new development has been the extraction of structural data, (geometry, cell orientation) from diffusion tensor magnetic resonance imaging of tissues; this allows the reconstruction of a 3-D detailed digital map of an organ in a few days, rather than the months-years necessary for histological reconstruction.

Funding Computational Biology Leeds is funded by project, programme and network grants from the BBSRC, EPSRC, MRC, BHF, EU and Sun Microsystems 

 

Current Projects

  • Regional differences in the electrical activity of SAN tissue (BHF) and acidotic ventricular tissue (BHF)
  • Engineering virtual cardiac tissue (EPSRC, MRC)
  • Reentrant arrhythmias and fibrillation (EPSRC)
 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Visualisation of cardiac motion; interpretation of electrical activity during ventricular fibrillation

Postgraduate studentship areas:

  • Computational modelling of normal & abnormal heart function.

See also:

Biktasheva IV, Anderson RA, Holden AV, Pervolaraki E, Wen FC Cardiac re-entry dynamics and self-termination in DT-MRI based model of human fetal heart Frontiers in Physics 5, 2018
DOI:10.3389/fphy.2018.00015
View abstract

Begg GA, Karim R, Oesterlein T, Graham LN, Hogarth AJ, Page SP, Pepper CB, Rhode K, Lip GYH, Holden AV, Plein S, Tayebjee MH Left atrial voltage, circulating biomarkers of fibrosis, and atrial fibrillation ablation. A prospective cohort study PLoS ONE 13, 2018
DOI:10.1371/journal.pone.0189936
View abstract

Begg GA, Karim R, Oesterlein T, Graham LN, Hogarth AJ, Page SP, Pepper CB, Rhode K, Lip GYH, Holden AV, Plein S, Tayebjee MH Intra-cardiac and peripheral levels of biochemical markers of fibrosis in patients undergoing catheter ablation for atrial fibrillation Europace 19 1944-1950, 2017
DOI:10.1093/europace/euw315
View abstract

Pervolaraki E, Dachtler J, Anderson RA, Holden AV Ventricular myocardium development and the role of connexins in the human fetal heart Scientific Reports 7, 2017
DOI:10.1038/s41598-017-11129-9
View abstract

Martsinkevich R, Stegemann B, Holden AV, Tayebjee MH Differences in right and left atrial structure and electrophysiology in ARVD, 2017
DOI:10.1093/europace/eux283.084

Colman MA, Perez Alday EA, Holden AV, Benson AP Trigger vs. substrate: Multi-dimensional modulation of QT-prolongation associated arrhythmic dynamics by a hERG channel activator Frontiers in Physiology 8, 2017
DOI:10.3389/fphys.2017.00757
View abstract

Marcinkevics R, O'Neill J, Law H, Pervolaraki E, Hogarth A, Russell C, Stegemann B, Holden AV, Tayebjee MH Multichannel electrocardiogram diagnostics for the diagnosis of arrhythmogenic right ventricular dysplasia. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of, 2017
DOI:10.1093/europace/eux124
View abstract

Begg GA, Lip GYH, Plein S, Tayebjee MH Circulating biomarkers of fibrosis and cardioversion of atrial fibrillation: A prospective, controlled cohort study Clinical Biochemistry 50 11-15, 2017
DOI:10.1016/j.clinbiochem.2016.09.008
View abstract

Begg GA, Holden AV, Lip GYH, Plein S, Tayebjee MH Assessment of atrial fibrosis for the rhythm control of atrial fibrillation International Journal of Cardiology 220 155-161, 2016
DOI:10.1016/j.ijcard.2016.06.144
View abstract

Testrow CP, Whittaker DG, Holden AV, Zhang H Modelling the effects of nifedipine on ventricular and myometrial cells of pregnant rats, 2016
View abstract

Atkinson L, Basharat A, Benson AP, Colman MA, Holden AV, Kagugube GW, Pervolaraki E Computational modelling of cardiac electrophysiological changes in malarial fever, 2016
View abstract

Hodgson S, Holden AV, Benson AP, Pervolaraki E Congenital heart block in a one-dimensional computational model of the human fetal heart, 2015

Kharche SR, Stary T, Colman MA, Biktasheva IV, Workman AJ, Rankin AC, Holden AV, Zhang H Effects of human atrial ionic remodelling byβ-blocker therapy on mechanisms of atrial fibrillation: a computer simulation. Europace 16 1524-1533, 2014
DOI:10.1093/europace/euu084
View abstract

Pervolaraki E, Hodgson S, Holden AV, Benson AP Towards computational modelling of the human foetal electrocardiogram: normal sinus rhythm and congenital heart block. Europace 16 758-765, 2014
DOI:10.1093/europace/eut377
View abstract

Benson AP, Bleakley A, Hodgson S, Holden AV, Pelech N, Palkhi E, Pervolaraki E, Whitfield C Computational modeling of human fetal normal sinus rhythm and arrhythmia Computing in Cardiology 40 37-40, 2013
View abstract

Pervolaraki E, Holden AV Spatiotemporal patterning of uterine excitation patterns in human labour. Biosystems 112 63-72, 2013
DOI:10.1016/j.biosystems.2013.03.012
View abstract

Pervolaraki E, Anderson RA, Benson AP, Hayes-Gill B, Holden AV, Moore BJR, Paley MN, Zhang H Antenatal architecture and activity of the human heart Interface Focus 3, 2013
DOI:10.1098/rsfs.2012.0065
View abstract

Aslanidi OV, Nikolaidou T, Zhao J, Smaill BH, Gilbert SH, Holden AV, Lowe T, Withers PJ, Stephenson RS, Jarvis JC, Hancox JC, Boyett MR, Zhang H Application of micro-computed tomography with iodine staining to cardiac imaging, segmentation, and computational model development IEEE Transactions on Medical Imaging 32 8-17, 2013
DOI:10.1109/TMI.2012.2209183
View abstract

Zhang H, Butters T, Adeniran I, Higham J, Holden AV, Boyett MR, Hancox JC Modeling the chronotropic effect of isoprenaline on rabbit sinoatrial node Frontiers in Physiology 3 JUL, 2012
DOI:10.3389/fphys.2012.00241
View abstract

Aslanidi OV, Al-Owais M, Benson AP, Colman M, Garratt CJ, Gilbert SH, Greenwood JP, Holden AV, Kharche S, Kinnell E, Pervolaraki E, Plein S, Stott J, Zhang H Virtual tissue engineering of the human atrium: modelling pharmacological actions on atrial arrhythmogenesis. Eur J Pharm Sci 46 209-221, 2012
DOI:10.1016/j.ejps.2011.08.014
View abstract

Pervolaraki E, Holden AV Human uterine excitation patterns leading to labour: Synchronization or propagation? Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 7223 LNCS 162-176, 2012
DOI:10.1007/978-3-642-28792-3_21
View abstract

Gilbert SH, Benoist D, Benson AP, White E, Tanner SF, Holden AV, Dobrzynski H, Bernus O, Radjenovic A Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI. Am J Physiol Heart Circ Physiol 302 H287-H298, 2012
DOI:10.1152/ajpheart.00824.2011
View abstract

Aslanidi OV, Colman MA, Stott J, Dobrzynski H, Boyett MR, Holden AV, Zhang HG 3D virtual human atria: A computational platform for studying clinical atrial fibrillation PROG BIOPHYS MOL BIO 107 156-168, 2011
DOI:10.1016/j.pbiomolbio.2011.06.011

Colman MA, Aslanidi OV, Stott J, Holden AV, Zhang HG Correlation Between P-Wave Morphology and Origin of Atrial Focal Tachycardia-Insights From Realistic Models of the Human Atria and Torso IEEE T BIO-MED ENG 58 2952-2955, 2011
DOI:10.1109/TBME.2011.2161305

Aslanidi O, Atia J, Benson AP, van den Berg HA, Blanks AM, Choi C, Gilbert SH, Goryanin I, Hayes-Gill BR, Holden AV, Li P, Norman JE, Shmygol A, Simpson NA, Taggart MJ, Tong WC, Zhang H Towards a computational reconstruction of the electrodynamics of premature and full term human labour Prog 107 183-92. Epub 2011 Jul 13.-183-92. Epub 2011 Jul 13., 2011
View abstract

Benson AP, Al-Owais M, Holden AV Quantitative prediction of the arrhythmogenic effects of de novo hERG mutations in computational models of human ventricular tissues EUR BIOPHYS J BIOPHY 40 627-639, 2011
DOI:10.1007/s00249-010-0663-2

Tong WC, Choi CY, Karche S, Holden AV, Zhang HG, Taggart MJ A Computational Model of the Ionic Currents, Ca2+ Dynamics and Action Potentials Underlying Contraction of Isolated Uterine Smooth Muscle PLOS ONE 6, 2011
DOI:10.1371/journal.pone.0018685

Benson A, Bernus O, Dierckx H, Gilbert S, Greenwood J, Holden A, Mohee K, Plein S, Radjenovic A, Ries ME, Smith G, Sourbron S, Walton R Construction and validation of anisotropic and orthotropic ventricular geometries for quantitative predictive cardiac electrophysiology Interface Focus 1 101-116, 2011

Benson AP, Bernus O, Holden AV, Zhang H QUANTIFICATION OF SPATIAL DYNAMICS OF CARDIAC ARRHYTHMIAS, 2011
DOI:10.1136/hrt.2010.213496.17

Holden AV Development and Application of Human Virtual Excitable Tissues and Organs: From Premature Birth to Sudden Cardiac Death ATLA-ALTERN LAB ANIM 38 87-99, 2010

Li P, Wei WJ, Cai X, Soeller C, Cannell MB, Holden AV Computational modelling of the initiation and development of spontaneous intracellular Ca2+ waves in ventricular myocytes, 2010
DOI:10.1098/rsta.2010.0146

Blanks AM, Tong WC, Benson AP, Holden AV Digital Reconstruction of the Fibre Architecture of the Pregnant Human Uterus In Vivo and In Vitro by Diffusion MRI., 2010

Gilbert SH, McConnell FJ, Holden AV, Sivananthan MU, Dukes-McEwan J The potential role of MRI in veterinary clinical cardiology VET J 183 124-134, 2010
DOI:10.1016/j.tvjl.2008.11.018

Jayasinghe ID, Li P, Holden AV, Crossman DJ, Cannell MB, Soeller C Dislocations and Helicoids in Myofibrillar Z-Disks of Mammalian Ventricular Myocytes and Implications for Calcium Handling BIOPHYSICAL JOURNAL 98 360A-360A, 2010

Holden AV, Gilbert SH, Benson AP Is Geometry or Dynamics More Important in Cardiac Arrhythmogenesis?, 2010
DOI:10.1007/978-3-642-12110-4_53

Zhang H, Zhang JQ, Holden AV Positive correlation between heart rate variability and stochastic nervous modulation - A computer simulation study Computers in Cardiology 36 437-440, 2009
View abstract

Li P, Wei W, Cai X, Soeller C, Cannell MB, Holden AV Evolution of intracellular ca<sup>2∈+∈</sup>waves from about 10,000 ryr clusters: Towards solving a computationally daunting task Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 5528 11-20, 2009
DOI:10.1007/978-3-642-01932-6_2
View abstract

Zhang HG, Garratt CJ, Kharche S, Holden AV Remodelling of cellular excitation (reaction) and intercellular coupling (diffusion) by chronic atrial fibrillation represented by a reaction-diffusion system PHYSICA D 238 976-983, 2009
DOI:10.1016/j.physd.2008.06.012

Li P, Holden AV Intracellular Ca2+ nonlinear wave behaviours in a three dimensional ventricular cell model PHYSICA D 238 992-999, 2009
DOI:10.1016/j.physd.2008.12.008

Zhang JQ, Holden AV, Monfredi O, Boyett MR, Zhang H Stochastic vagal modulation of cardiac pacemaking may lead to erroneous identification of cardiac "chaos" CHAOS 19, 2009
DOI:10.1063/1.3141426

Bernus O, Holden AV, Panfilov AV Nonlinear waves in excitable media: Approaches to cardiac arrhythmias Preface PHYSICA D 238 V-VIII, 2009
DOI:10.1016/S0167-2789(09)00119-5

Soeller C, Jayasinghe ID, Li P, Holden AV, Cannell MB Three-dimensional high-resolution imaging of cardiac proteins to construct models of intracellular Ca2+ signalling in rat ventricular myocytes EXP PHYSIOL 94 496-508, 2009
DOI:10.1113/expphysiol.2008.043976

Tong WC, Choi CY, Zhang HG, Taggart M, Holden AV Construction of Models of Electrical Activity of Myometrial Cells during Different Stages of Pregnancy., 2009

Li P, Soeller C, Cannell M, Wei WJ, Cai X, Holden AV THE ROLE OF STRUCTURAL BIFURCATION OF Z-DISKS ON REGULATING SPONTANEOUS CALCIUM ACTIVITIES IN CARDIAC MYOCYTES: A THEORETICAL INVESTIGATION J PHYSIOL SCI 59 131-131, 2009

Gilbert SH, Bernus O, Holden AV, Benson AP A Quantitative Comparison of the Myocardial Fibre Orientation in the Rabbit as Determined by Histology and by Diffusion Tensor-MRI, 2009

Dierckx H, Benson AP, Gilbert SH, Ries ME, Holden AV, Verschelde H, Bernus O Intravoxel Fibre Structure of the Left Ventricular Free Wall and Posterior Left-Right Ventricular Insertion Site in Canine Myocardium Using Q-Ball Imaging, 2009

Benson AP, Al-Owais M, Tong WC, Holden AV HERG Effects on Ventricular Action Potential Duration and Tissue Vulnerability: A Computational Study, 2009

Kharche S, Garratt CJ, Boyett MR, Inada S, Holden AV, Hancox JC, Zhang HG Atrial proarrhythmia due to increased inward rectifier current (I-K1) arising from KCNJ2 mutation - A simulation study PROG BIOPHYS MOL BIO 98 186-197, 2008
DOI:10.1016/j.pbiomolbio.2008.10.010

Kharche S, Seemann G, Margetts L, Leng J, Holden AV, Zhang HG Simulation of clinical electrophysiology in 3D human atria: a high-performance computing and high-performance visualization application, 2008
DOI:10.1002/cpe.1332

Peitersen T, Grunnet M, Benson AP, Holden AV, Holstein-Rathlou NH, Olesen SP Computational analysis of the effects of the hERG channel opener NS1643 in a human ventricular cell model HEART RHYTHM 5 734-741, 2008
DOI:10.1016/j.hrthm.2008.02.026

Benson AP, Aslanidi OV, Zhang H, Holden AV The canine virtual ventricular wall: A platform for dissecting pharmacological effects on propagation and arrhythmogenesis PROG BIOPHYS MOL BIO 96 187-208, 2008
DOI:10.1016/j.pbiomolbio.2007.08.002

Benson AP, Gilbert SH, Ries ME, Aslanidi OV, Zhang H, Boyett MR, Dobrzynski H, Holden AV 0.2mm cubic voxel reconstruction of rabbit heart geometry and architecture using diffusion tensor magentic resonance imaging. Proceedings of the Physiological Society, 2008

Benson AP, Lawrenson JA, Gilbert SH, Holden AV Quantifying effects of class I anti-arrhythmic drugs in human virtual cardiac tissues LECT NOTES COMPUT SC 5104 203-208, 2008
View abstract

Benson AP, Hodgson EK, Bernus O, Holden AV Quantifying the Effects of Ischaemia on Electrophysiology and the ST Segment of the ECG in Human Virtual Ventricular Cells and Tissues, 2008

Zhang H, Kharche S, Holden AV, Hancox JC Repolarisation and vulnerability to re-entry in the human heart with short QT syndrome arising from KCNQ1 mutation - A simulation study PROG BIOPHYS MOL BIO 96 112-131, 2008
DOI:10.1016/j.pbiomolbio.2007.07.020

Benson AP, Gilbert SH, Li P, Newton SM, Holden AV Reconstruction and Quantification of Diffusion Tensor Imaging-Derived Cardiac Fibre and Sheet Structure in Ventricular Regions used in Studies of Excitation Propagation MATH MODEL NAT PHENO 3 101-130, 2008
DOI:10.1051/mmnp:2008083

Liu J, Holden AV, Zhang H Actions of an external electrical shock on human atrial excitation - A computer model study Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 4561 LNCS 659-667, 2007
View abstract

Kharche S, Garratt CJ, Holden AV, Zhang H Stability of scroll excitation waves in human atria during fibrillation: A computational study Computers in Cardiology 34 285-288, 2007
DOI:10.1109/CIC.2007.4745477
View abstract

Kharche S, Seemann G, Leng J, Holden AV, Garratt CJ, Zhang H Scroll waves in 3D virtual human atria: A computational study Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 4466 LNCS 129-138, 2007
View abstract

Gilbert SH, Benson AP, Li P, Holden AV Regional localisation of left ventricular sheet structure: integration with current models of cardiac fibre, sheet and band structure EUR J CARDIO-THORAC 32 231-249, 2007
DOI:10.1016/j.ejcts.2007.03.032

Benson AP, Halley G, Li P, Tong WC, Holden AV Virtual cell and tissue dynamics of ectopic activation of the ventricles CHAOS 17, 2007
DOI:10.1063/1.2404634

Tsyganov MA, Biktashev VN, Brindley J, Holden AV, Ivanitsky GR Waves in systems with cross-diffusion as a new class of nonlinear waves PHYS-USP+ 50 263-286, 2007
DOI:10.1070/PU2007v050n03ABEH006114

Benson AP, Ries ME, Holden AV Effects of geometry and architecture on re-entrant scroll wave dynamics in human virtual ventricular tissues LECT NOTES COMPUT SC 4466 200-209, 2007
View abstract

Zhang H, Zhao Y, Lei M, Dobrzynski H, Liu JH, Holden AV, Boyett MR Computational evaluation of the roles of Na+ current, i(Na), and cell death in cardiac pacemaking and driving American Journal of Physiology: Heart and Circulatory Physiology 292 165-174, 2007
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Benson AP, Rhodes AS, Holden AV Dynamic action potential clamp as a tool for comparing ionic mechanisms in cardiac cell models Proceedings of the Physiological Society 8 pp.30-, 2007

Gilbert SH, Benson AP, Li P, Holden AV Visualisation of Dog Myocardial Structure from Diffusion Tensor Magnetic Resonance Imaging: The Paradox of Uniformity and Variability. Lecture Notes in Computer Science 4466 403-412, 2007
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Lawrenson JA, Benson AP, Holden AV Reduced conduction velocity caused by class Ib anti-arrythmic drugs contributes to both their anti- and pro-arrythmic effects in human virtual ventricular tissues Proceedings of the Physiological Society 8 pp.9-, 2007

Benson AP, Holden AV Cardiac geomtery and architecture affect dynamics of re-entrant scroll waves in human virtual tissues None, 2007

Li P, Lancaster M, Holden AV A three dimensional ventricular E-Cell (3Dv E-Cell) with stochastic intracellular Ca2+ handling, 2007

Zhang H, Zhao Y, Lei M, Dobrzynski H, Liu JH, Holden AV, Boyett MR Computational evaluation of the roles of Na+ current, i(Na), and cell death in cardiac pacemaking and driving AM J PHYSIOL-HEART C 292 H165-H174, 2007
DOI:10.1152/ajpheart.01101.2005

Zhang H, Liu JH, Holden AV Computing the age-related dysfunction of cardiac pacemaker Computers in Cardiology 33 665-668, 2006
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Tong WC, Holden AV Engineering stable pacemaking at physiological rate in virtual ventricular myocytes Computers in Cardiology 33 781-784, 2006
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Tong WC, Holden AV Bifurcation analysis of genetically engineered pacemaking in mammalian heart J BIOL PHYS 32 169-172, 2006
DOI:10.1007/s10867-006-9004-1

Holden AV, Aslanidi OV, Benson AP, Clayton RH, Halley G, Li P, Tong WC The virtual ventricular wall: A tool for exploring cardiac propagation and arrhythmogenesis J BIOL PHYS 32 355-368, 2006
DOI:10.1007/s10867-006-9020-1

Seemann G, Hoper C, Sachse FB, Dossel O, Holden AV, Zhang HG Heterogeneous three-dimensional anatomical and electrophysiological model of human atria PHILOS T R SOC A 364 1465-1481, 2006
DOI:10.1098/rsta.2006.1781

Benson AP, Clayton RH, Holden AV, Kharche S, Tong WC Endogenous driving and synchronization in cardiac and uterine virtual tissues: bifurcations and local coupling PHILOS T R SOC A 364 1313-1327, 2006
DOI:10.1098/rsta.2006.1772

Biktasheva IV, Holden AV, Biktashev VN Localization of response functions of spiral waves in the Fitzhugh-Nagumo system INT J BIFURCAT CHAOS 16 1547-1555, 2006

Aslanidi OV, Benson AP, Holden AV, Zhang HM Quantifying the effects of class III drugs on the canine ventricular tissue Proceedings of the Physiological Society 3 pp.92-, 2006

Benson AP, Aslanidi OV, Zhang HM, Holden AV A model of canine cardiac ventricular wall electrophysiology Proceedings of the Physiological Society 3 pp.91-, 2006

Benson AP, Aslanidi OV, Zhang HM, Holden AV A three dimensional model of canine cardiac ventricular wall electrophysiology Computers in Cardiology 789-792, 2006

Aslanidi OV, Clayton RH, Lambert JL, Holden AV Dynamical and cellular electrophysiological mechanisms of ECG changes during ischaemia J THEOR BIOL 237 369-381, 2005
DOI:10.1016/j.jtbi.2005.04.022

Aslanidi OV, Biktashev VN, Biktasheva IV, Clayton RH, Holden AV 21 Towards understanding the physical basis of re-entrant cardiac arrhythmias Studies in Multidisciplinarity 3 389-410, 2005
DOI:10.1016/S1571-0831(06)80025-0

Kharche S, Holden AV, Zhang H Vulnerability in a one-dimensional transmural model of human ventricular tissue in heart failure Computers in Cardiology 32 563-566, 2005
DOI:10.1109/CIC.2005.1588163
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Zhang H, Liu JH, Garratt CJ, Holden AV Competitive interactions between ectopic foci and reentry in virtual human atrium Computers in Cardiology 32 73-76, 2005
DOI:10.1109/CIC.2005.1588037
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Zhang H, Tong WC, Garratt CJ, Holden AV Stability of genetically engineered cardiac pacemaker - Role of intracellular Ca2+ handling Computers in Cardiology 32 969-972, 2005
DOI:10.1109/CIC.2005.1588270
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Boyett MR, Li J, Inada S, Dobrzynski H, Schneider JE, Holden AV, Zhang HG Imaging the heart: computer 3-dimensional anatomic models of the heart JOURNAL OF ELECTROCARDIOLOGY 38 113-120, 2005
DOI:10.1016/j.jelectrocard.2005.06.102

Zhang H, Garratt CJ, Holden AV Functional conduction alternans facilitates the transition from rapid foci to reentry in homogeneous virtual human atrial tissue, 2005

Zhang HG, Garratt CJ, Zhu JJ, Holden AV Role of up-regulation of I-K1 in action potential shortening associated with atrial fibrillation in humans CARDIOVASC RES 66 493-502, 2005
DOI:10.1016/j.cardiores.2005.01.020

Aslanidi OV, Holden AV Transmurai heterogeneity and vulnerability to re-entry in virtual cardiac tissue, 2005

Benson AP, Holden AV Propagation of calcium-induced ectopic beats in virtual ventricular tissues, 2005

Clayton RH, Holden AV Dispersion of cardiac action potential duration and the initiation of re-entry: A computational study BioMedical Engineering Online 4, 2005
DOI:10.1186/1475-925X-4-11
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Holden AV The sensitivity of the heart to static magnetic fields PROG BIOPHYS MOL BIO 87 289-320, 2005
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Kharche S, Zhang H, Clayton RC, Holden AV Hypertrophy in rat virtual left ventricular cells and tissue FUNCTIONAL IMAGING AND MODELING OF HEART, PROCEEDINGS 3504 153-161, 2005

Tong WC, Holden AV Induced pacemaker activity in virtual mammalian ventricular cells LECT NOTES COMPUT SC 3504 226-235, 2005
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Benson AP, Li P, Hsu EW, Holden AV Reconstruction and visualisation of cardiac ventricualr geomtery and architecture from diffusion tensor magnetic resonance imaging Journal of Physiology, 2005

Aslanidi OV, Brodlie KW, Clayton RH, Handley J, Holden AV, Wood J Remote visualization and computational steering of cardiac virtual tissues using gViz, 2005
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Benson AP, Benson AP, Holden AV Calcium oscillations and ectopic beats in virtual ventricular myocytes and tissues: Bifurcations, autorhythmicity and propagation Lecture Notes in Computer Science 3504 304-313, 2005
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Aslanidi OV, Lambert JL, Srinivasan NT, Holden AV Virtual ventricular wall: Effects of pathophysiology and pharmacology on transmural propagation FUNCTIONAL IMAGING AND MODELING OF HEART, PROCEEDINGS 3504 162-171, 2005

Biktasheva IV, Biktashev VN, Holden AV Wavebreaks and self-termination of spiral waves in a model of human atrial tissue Lecture Notes in Computer Science 3504 293-303, 2005
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Zhang H, Zhu JJ, Garratt CJ, Holden AV Computational study of the relative contribution of channel and gap junction remodelling on human atrial conduction during fibrillation Computers in Cardiology 31 141-144, 2004
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Holden AV The fine-scale architecture of defibrillation CARDIOVASC RES 64 384-386, 2004
DOI:10.1016/j.cardiores.2004.09.015

Biktashev VN, Brindley J, Holden AV, Tsyganov MA Pursuit-evasion predator-prey waves in two spatial dimensions Chaos 14 988-994, 2004
DOI:10.1063/1.1793751
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Tsyganov MA, Brindley J, Holden AV, Biktashev VN Soliton-like phenomena in one-dimensional cross-diffusion systems: a predator-prey pursuit and evasion example Physica D - Nonlinear Phenomena 197 18-33, 2004
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Clayton RH, Holden AV Propagation of normal beats and re-entry in a computational model of ventricular cardiac tissue with regional differences in action potential shape and duration PROG BIOPHYS MOL BIO 85 473-499, 2004
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Rayner SM, Garratt CJ, Holden AV, Zhang H The role of intracellular CA(2+) handling in determining stability of a genetically engineered pacemaker Heart 90 pp.125-, 2004
DOI:10.1136/hrt.2002.007765
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Holden AV Neural coding by correlation? Nature 428 382-, 2004
DOI:10.1038/428382a
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Holden AV Signal processing - Neural coding by correlation? NATURE 428 382-382, 2004
DOI:10.1038/428382a

Zhang H, Holden AV Defibrillation threshold computed from normal and supernormal excitable cardiac tissue MATHEMATICAL BIOSCIENCES 188 175-190, 2004
DOI:10.1016/j.mbs.2003.10.003

Aslanidi GV, Aslanidi OV, Tsyganov MA, Holden AV, Ivanitsky GR Conditions causing wavefront instability in a growing colony of bacterial cells with chemotactic activity Doklady Biochemistry and Biophysics 394 18-20, 2004
DOI:10.1023/B:DOBI.0000017145.14319.70

Benson AP, Tong WC, Clayton RH, Holden AV Induction of autorhythmicity in virtual ventricular myocytes and tissue Journal of Physiology 561 pp.22-, 2004

Kharche S, Zhang H, Clayton R, Holden AV Simulation of hypertrophy in rat left ventricular cells, 2004
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Zhang H, Zhu JJ, Garratt CJ, Holden AV Relative role of electrical and gap junctional remodelling on atrial conduction velocity in virtual human atrial tisssue Heart Rhythm 1 pp.256-, 2004
DOI:10.1016/j.hrthm.2004.06.011

Clayton RH, Holden AV Filament behavior in a computational model of ventricular fibrillation in the canine heart IEEE T BIO-MED ENG 51 28-34, 2004
DOI:10.1109/TBME.2003.820356

Clayton RH, Holden AV Virtual tissue engineering of the heart INT J BIFURCAT CHAOS 13 3531-3534, 2003

Li Z, Holden AV, Orchard CH, Zhang H Modeling excitation and propagation of action potentials across inhomogeneous ventricular tissue, 2003

Dobrzynski H, Zhang HG, Wright SE, Holden AV, Boyett MR Structure-function relationships of the sinoatrial node, 2003
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Zhang H, Garrat CJ, Holden AV Onset and termination of reentrant excitation in homogeneous human virtual atrial tissue, 2003

Clayton RH, Holden AV, Tong WC Can endogenous, noise-triggered early after-depolarizations initiate reentry in a modified Luo-Rudy ventricular virtual tissue?, 2003

Aslanidi OV, Clayton RH, Holden AV, Phillips HK, Ward RJ Vulnerability to reentry, and drift, stability and breakdown of spiral waves in a linear gradient of G(K) in a Luo-Rudy 1 virtual ventricular tissue, 2003

Sachse FB, Seemann G, Mohr MB, Holden AV Mathematical modeling of cardiac electro-mechanics: From protein to organ, 2003
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Aslanidi OV, Holden AV A simple model for interaction of voltage and calcium dynamics in virtual ventricular tissue INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS 13 3873-3886, 2003

Zhang H, Noble D, Cannell M, Orchard CH, Lancaster M, Jones SA, Boyett MR, Holden AV, Jafri MS, Sobie EA, Lederer WJ, Demir SS, Michailova A, Delprincipe F, Egger M, Niggli E, Smith GL, Loughrey CM, MacQuaide N, Dempster J, Trafford AW Dynamics of cardiac intracellular Ca2+ handling - From experiments to virtual cells INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS 13 3535-3560, 2003

Biktasheva IV, Biktashev VN, Dawes WN, Holden AV, Saumarez RC, Savill AM Dissipation of the excitation front as a mechanism of self-terminating arrhythmias, 2003
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Clayton RH, Holden AV Dynamics and interaction of filaments during reentry and fibrillation in mammalian virtual ventricular tissue, 2003

Kremmydas GP, Holden AV Spiral wave meandering in models of ventricular tissue as an antiarrhythmic target Computers in Cardiology 30 785-788, 2003
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Zhang H, Zhu JJ, Garratt CJ, Holden AV Cellular modelling of electrical remodelling in two different models of human atrial myocytes Computers in Cardiology 30 777-780, 2003
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Tsyganov MA, Brindley J, Holden AV, Biktashev VN Quasisoliton interaction of pursuit-evasion waves in a predator-prey system Physical Review Letters 91 pp.218102-, 2003
DOI:10.1103/PhysRevLett.91.218102
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Tsyganov MA, Brindley J, Holden AV, Biktashev VN Quasisoliton Interaction of Pursuit-Evasion Waves in a Predator-Prey System Physical Review Letters 91 pp.218102-, 2003
DOI:10.1103/PhysRevLett.91.218102

Clayton RH, Holden AV Effect of regional differences in cardiac cellular electrophysiology on the stability of ventricular arrhythmias: a computational study. Phys Med Biol 48 95-111, 2003
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Clayton RH, Holden AV International Journal of Bifurication and Chaos in Applied Sciences and Engnieering: Editorial International Journal of Bifurcation and Chaos in Applied Sciences and Engineering 13 3531-3534, 2003
DOI:10.1142/S0218127403008752

Zhang H, Garrat CJ, Holden AV Onset and termination of re-entrant excitation in homogeneous human virtual atrial tissue International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3631-3644, 2003

Li Z, Zhang H, Orchard CH, Holden AV Modelling excitation and propagation of action potentials across inhomogeneous ventricular tissue International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3845-3864, 2003

Biktasheva IV, Biktashev VN, Dawes WN, Holden AV, Saumarez RC, Savill AM Dissipation of the excitation front as a mechanism of self-terminating arrhythmias International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3645-3656, 2003

Clayton RH, Holden AV, Tong WC Can endogeneous, noise-triggered early after-depolarisations initiate re-entry in a modified Luo-Rudy ventricular virtual tissue? International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3835-3844, 2003

Clayton RH, Holden AV Virtual tissue engineering of cardiac muscle: Computational aspects None 431-441, 2003

Aslanidi OV, Clayton RH, Holden AV, Phillips H, Ward R Vulnerability to re-entry, and drift, stability and breakdown of spiral waves in a linear gradient of Gk in a Luo-Rudy1 virtual ventricular tissue International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3865-3872, 2003

Clayton RH, Holden AV Dynamics and interaction of filaments during re-entry and fibrillation in mammalian virtual ventricular tissue International Journal of Bifurcations and Chaos in Applied Sciences and Engineering pp.00-, 2003

Dobrzynski H, Zhang H, Wright SE, Holden AV, Boyett MR Structure-function relationships of the sinoatrial node International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3621-3630, 2003

Zhang HG, Dobrzynski H, Holden AV, Boyett MR Heterogeneous sinoatrial node of rabbit heart - Molecular and electrical mapping and biophysical reconstruction FUNCTIONAL IMAGING AND MODELING OF THE HEART, PROCEEDINGS 2674 132-140, 2003

Chen M, Tucker JV, Clayton RH, Holden AV Constructive volume geometry applied to visualisation of cardiac anatomy and electrophysiology International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3591-3604, 2003

Sachse FB, Seeman G, Mohr MB, Holden AV Mathematical modelling of cardiac electromechanics: from protein to organ International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 13 3747-3756, 2003

Chen M, Clayton RH, Holden AV, Tucker JV Visualising cardiac anatomy using constructive volume geometry LECT NOTES COMPUT SC 2674 30-38, 2003
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Clayton RH, Holden AV Regional differences in action potential duration and stability of re-entry: insights from computational models, 2002

Biktasheva IV, Holden AV, Zhang H Stability, period and meander of spiral waves in two human virtual atrial tissues, 2002

Clayton RH, Holden AV Computational framework for simulating the mechanisms and ECG of re-entrant ventricular fibrillation. Physiol Meas 23 707-726, 2002
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Garratt CJ, Holden AV, Zhang H Cellular modelling of human atrial tissue remodelling produced by atrial fibrillation, 2002

Aslanidi O, Mornev OA, Holden AV Bidomain virtual ventricular tissue: role of the external bath in defibrillation, 2002

Aslanidi OV, Bailey A, Biktashev VN, Clayton RH, Holden AV Enhanced self-termination of re-entrant arrhythmias as a pharmacological strategy for antiarrhythmic action. Chaos 12 843-851, 2002
DOI:10.1063/1.1500496
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Elkin YE, Biktashev VN, Holden AV Waves of constant shape and the structure of the "rotors boundary" in excitable media CHAOS SOLITON FRACT 14 385-395, 2002

Clayton RH, Holden AV From excitable media to virtual cardiac tissue CHAOS SOLITON FRACT 13 1579-1580, 2002

Clayton RH, Parkinson K, Holden AV Re-entry in computational models of ischaemic myocardium CHAOS SOLITON FRACT 13 1671-1683, 2002
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Poole MJ, Holden AV, Tucker JV Hierarchical reconstructions of cardiac tissue CHAOS SOLITONS&FRACTALS 13 1581-1612, 2002

Zhang H, Holden AV, Boyett MR Computational approaches to the ionic basis of pacemaker activity - from channel kinetics to the regional differences in rhythm CHAOS SOLITONS&FRACTALS 13 1631-1642, 2002

Holden AV, Biktashev VN Computational biology of propagation in excitable media models of cardiac tissue CHAOS SOLITONS&FRACTALS 13 1643-1658, 2002

Kremmydas GP, Holden AV Spiral-wave meandering in reaction-diffusion models of ventricular muscle CHAOS SOLITON FRACT 13 1659-1669, 2002
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Clayton RH, Holden AV Dynamics and interaction of filaments in a computational model of re-entrant ventricular fibrillation PHYS MED BIOL 47 1777-1792, 2002

Zhang H, Holden AV, Noble D, Boyett MR Analysis of the chronotropic effect of acetylcholine on sinoatrial node cells. J Cardiovasc Electrophysiol 13 465-474, 2002
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Biktashev VN, Holden AV, Mironov SF, Pertsov AM, Zaitsev AV Three-dimensional organisation of re-entrant propagation during experimental ventricular fibrillation. Chaos, Solitons and Fractals 13 1713-1733, 2002
DOI:10.1016/S0960-0779(01)00164-3

Zhang H, Holden AV, Boyett MR Sustained inward current and pacemaker activity of mammalian sinoatrial node. Journal of Cardiovascular Electrophysiology 13 809-812, 2002
DOI:10.1046/j.1540-8167.2002.00809.x

Clayton RH, Holden AV Filament dynamics in a computational model of re-entrant fibrillation in anatomically detailed canine ventricular anatomy, 2002
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Aslanidi OV, Mornev OA, Holden AV Low-voltage defibrillation in bidomain virtual ventricular tissue: Effect of the bath, 2002

Clayton RH, Holden AV Simulating the ECG of ventricular tachyarrhythmias, 2002
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Clayton RH, Holden AV A method to quantify the dynamics and complexity of re-entry in computational models of ventricular fibrillation. Physics in Medicine and Biology 47 225-238, 2002
DOI:10.1088/0031-9155/47/2/304

Aslanidi OV, Biktashev VN, Clayton RH, Holden AV Differential meander of re-entrant spiral waves in mammalian virtual ventricular tissue, 2001

Zhang H, Dobrzynski H, Kodama I, Takagishi Y, Holden AV, Boyett MR How does the sinoatrial node drive the atrium?, 2001

Boyett MR, Holden AV, Zhang H Engineering virtual cardiac tissue. Briefings in Bioinformatics 2 233-244, 2001
DOI:10.1093/bib/2.3.233

Biktashev VN, Holden AV Characterisation of patterned irregularity in locally interacting, spatially extended systems: Ventricular fibrillation Chaos 11 653-664, 2001
DOI:10.1063/1.1380429
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Zhang H, Holden AV, Boyett MR Modeling the effect of beta-adrenergic stimulation on the rabbit sinoatrial node J PHYSIOL-LONDON 533 38P-39P, 2001

Zhang H, Holden AV, Boyett MR Mathematical analysis of intracellular Ca2+ regulation of the pacemaker activity of rabbit sinoatrial node J PHYSIOL-LONDON 533 30P-31P, 2001

Biktashev VN, Holden AV, Mironov SF, Pertsov AM, Zaitsev AV On two mechanisms of the domain structure of ventricular fibrillation INT J BIFURCAT CHAOS 11 1035-1051, 2001

Zhang H, Holden AV, Boyett MR Gradient model versus mosaic model of the sinoatrial node CIRCULATION 103 584-588, 2001

Biktashev VN, Holden AV, Mironov SF, Pertsov AM, Zaitsev AV On two mechanisms of the domain structure of ventricular fibrillation International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 11 1035-1052, 2001
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Boyett MR, Zhang H, Al-Garny A, Holden AV Control of pacemaker activity of the sinoatrial node by intracellular Ca(2+). Experiments and modelling Philosophical Transactions of the Royal Society of London, Series A: Mathematical, Physical and Engineering Sciences 359 1091-1110, 2001
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Zhang H, Holden AV, Boyett MR Computer modelling of the sinoatrial node Bioelectromagnetics, 2001

Aslanidi OV, Clayton RH, Holden AV Re-entry in the Luo-Rudy ventricular tissue model with different models of Ca2+ dynamics, 2001

Clayton RH, Bailey A, Biktashev VN, Holden AV Re-entrant cardiac arrhythmias in computational models of Long QT myocardium Journal of Theoretical Biology 208 215-225, 2001
DOI:10.1006/jtbi.2000.2212

Zhang H, Zhao Y, Lei M, Dobrzynski H, Liu JH, Holden AV, Boyett MR Computational evaluation of the roles of Na+ current, i(Na), and cell death in cardiac pacemaking and driving American Journal of Physiology: Heart and Circulatory Physiology 292 165-174, 2001
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Clayton RH, Holden AV Computational simulation of multiple wavelet re-entry and fibrillatory conduction shows differences in the ECG characteristics of each mechanism, 2000

Zhang H, Holden AV, Kodama I, Honjo H, Lei M, Varghese T, Boyett MR Mathematical models of action potentials in the periphery and centre of the rabbit sinoatrial node American Journal of Physiology 279 397-421, 2000

Clayton RH, Yu DJ, Small M, Biktashev VN, Harrison RG, Holden AV Linear and nonlinear characteristics of ECG signals produced by simulations of ventricular tachyarrhythmias, 1999

Biktashev VN, Biktasheva IV, Holden AV, Tsyganov MA, Brindley J, Hill NA Spatiotemporal irregularity in an axcitable medium with shear flow. Physical Review E (Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics) 60(2) 1897-1900, 1999

Biktashev VN, Holden AV, Mironov SF, Perstov AM, Zaitsev AV Three dimensional aspects of re-entry in experimental and numerial models of ventricular fibrillation International Journal of Bifurcations and Chaos in Applied Sciences and Engineering 9 695-704, 1999

Clayton RH, Bailey A, Biktashev VN, Holden AV Re-entrant arrhythmias in simulations of the Long-QT syndrome, 1999

Biktashev VN, Holden AV, Tsyganov MA, Brindley J, Hill NA Excitation Wave Breaking in Excitable Media with Linear Shear Flow Physical Review Letters 81 2815-2818, 1998
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Biktashev VN, Holden AV Deterministic Brownian motion in the hypermeander of spiral waves Physica D - Nonlinear Phenomena 116 342-354, 1998

Biktashev VN, Holden AV Re-entrant waves and their elimination in a model of mammalian ventricular tissue. Chaos 8 48-56, 1996