Faculty of Biological Sciences

Dr Al Benson

BSc, PhD, Leeds
Lecturer in Cardiovascular Science
School of Biomedical Sciences

Contact:  Garstang 7.56a, +44(0) 113 34 32557, email address for  

Research Interests

Computational modelling of cardiovascular physiology

My research interests are in the use of computational models, combined with magnetic resonance and other experimental techniques, to study cardiovascular physiology in health and disease. A particular focus has been the study of cardiac arrhythmias and exercise intolerance in heart failure.

This work is carried out as part of the Cardiovascular, Sports and Exercise Sciences research group.

Cardiac arrhythmias

Cardiac arrhythmias are a major cause of mortality and morbidity. Ventricular fibrillation is an often fatal arrhythmia in which the heart’s normal rhythm is disturbed when multiple electrical wavefronts continually re-excite the same tissue (re-entry); synchronous contraction of the ventricles is lost, circulation of the blood ceases and death occurs. Individuals with heart failure have a significantly increased risk of developing such arrhythmias.

Computational cardiac models provide tools for examining the mechanisms underlying the onset of such arrhythmias, and interventions aimed at either preventing this onset or restoring normal sinus rhythm, as the data they provide can be dissected in time and space, and by parameters. We develop biophysically-detailed computational models of the heart (at the sub-cellular, cellular, tissue and organ levels), and use these models to examine the roles that the structural (anatomical) and functional (electrophysiological and mechanical) changes seen in heart failure have on the initiation, maintenance and termination of cardiac arrhythmias such as ventricular fibrillation.

To facilitate this, we have recently developed, in collaboration with Professor Ed White and Dr Olivier Bernus, an experimental “pipeline” where physiological measurements, optical mapping, novel diffusion tensor magnetic resonance imaging (DT-MRI) measurements and computational simulations can all be linked to study mechanisms leading to the initiation of cardiac arrhythmias.

 


Top: Electrocardiogram (ECG) showing degeneration from normal sinus rhythm (NSR) to ventricular tachycardia (VT) then ventricular fibrillation (VF). Middle: Two-dimensional models can be used to examine the underlying electrical wave propagation and the functional mechanisms that cause transitions between the different states: plane waves for NSR, a single re-entrant spiral wave for VT, and multiple re-entrant waves for VF (red is excited tissue, blue is resting tissue). Action potentials recorded from sites indicated by asterisks are shown below. Bottom: Structural influences on wave behaviour can be examined by incorporating DT-MRI data into the models, in this case a human left ventricular wedge preparation. See Benson et al. (Interface Focus 1, 101-116, 2011) for details.

 

Exercise intolerance

The ability to sustain muscular exercise is a key determinant of health, quality of life, and mortality. Poor exercise tolerance contributes to a downward spiral of inactivity, which is an “actual cause” of chronic disease, and the cardinal symptom of heart failure is a significant exercise intolerance which limits heart failure patients to a relatively sedentary lifestyle. However, the mechanisms limiting exercise tolerance remain poorly understood. Individuals capable of high rates of oxidative phosphorylation are able to tolerate sustained exercise at high levels. Achieving these high rates depends upon the effective integration of the physiological systems involved in O2 delivery and utilisation, clearance of CO2, and buffering of acid-producing reactions. However, because most conditions of physical activity are nonsteady-state, it is the integrated dynamics of these physiological systems that are most strongly related to exercise tolerance and longevity. Computational models allow us to study the intricately integrated (and therefore non-intuitive) relationships that exist between the different components of such a complex physiological system.

Working closely with Dr Harry Rossiter and Dr Carrie Ferguson, we examine how the pulmonary, circulatory and muscular systems integrate during dynamic activity across the continuum of biological function, from elite athletes to heart failure patients. Experimental data – obtained using cardiopulmonary exercise testing (CPX), near-infrared spectroscopy (NIRS), magnetic resonance spectroscopy (MRS) and other techniques – are used to develop novel computational models integrating physiological systems dynamics. The data generated by these experiments and computational models help us understand how systems dynamics conflate to produce the rapid O2 uptake (VO2) kinetics that are a major determinant of exercise tolerance, and thereby contribute to improving exercise performance, health, quality of life, and longevity.

 

 

We have recently developed, optimised and validated a computational model integrating O2 exchange and transport in the pulmonary, circulatory, and muscular systems in healthy adults during moderate-intensity exercise. The model pulmonary O2 uptake (VO2P; red line, left) accurately predicts experimental CPX VO2P measurements (squares, left), and allows the difference between muscle and pulmonary VO2 kinetics (described by time constants; τ) to be quantified for a range of circulatory dynamics (right). See Benson, Grassi & Rossiter (Journal of Applied Physiology 115, 743-755, 2013) for details.

 

Faculty Research and Innovation

Modules managed

BMSC2229 - Experimental Skills in Medical Sciences

Modules taught

BMSC1103 - Basic Laboratory and Scientific Skills
BMSC1213 - Basic Laboratory and Scientific Skills 2
BMSC2120 - Scientific Skills
BMSC2229 - Experimental Skills in Medical Sciences
BMSC3138 - Cellular Cardiology
BMSC3233/34/35/36 - Advanced topics for BMS students II
BMSC3301 - Research Project in Biomedical Sciences
MEDI2201 - Control and Movement

Centre membership: The Multidisciplinary Cardiovascular Research Centre (MCRC)

Dr Eleftheria Pervolaraki  (Visiting Research Fellow)

Bioimaging and modelling of human cardiac foetal and neonatal development; enabling early diagnosis of disorders and evaluation of their treatment. 

Dr Kathleen Wright  (Senior Scientific Officer in Cardiovascular Science)

Providing laboratory research support for multiple PIs, training new staff and laboratory/office management 


Postgraduates

Sophie Hampson (Primary supervisor) 50% FTE
Harley Stevenson-Cocks (Primary supervisor) 50% FTE
Matthew Chadwick (Co-supervisor) 30% FTE
Matthew Davies (Co-supervisor) 30% FTE

Benson AP, Bowen TS, Ferguson C, Murgatroyd SR, Rossiter HB Data collection, handling and fitting strategies to optimize accuracy and precision of oxygen uptake kinetics estimation from breath-by-breath measurements. Journal of Applied Physiology -,
DOI:10.1152/japplphysiol.00988.2016
View abstract

Davies MJ, Benson AP, Cannon DT, Marwood S, Kemp GJ, Rossiter HB, Ferguson C Dissociating external power from intramuscular exercise intensity during intermittent bilateral knee-extension in humans. J Physiol -, 2017
DOI:10.1113/JP274589
View abstract

Whittaker DG, Ni H, Benson AP, Hancox JC, Zhang H Modelling the effects of disopyramide on short QT syndrome variant 1 in the human ventricles, 2017
DOI:10.22489/CinC.2016.003-435
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

Keir DA, Benson AP, Love LK, Robertson TC, Rossiter HB, Kowalchuk JM Influence of muscle metabolic heterogeneity in determining the VO<inf>2p</inf>kinetic response to ramp-incremental exercise Journal of Applied Physiology 120 503-513, 2016
DOI:10.1152/japplphysiol.00804.2015
View abstract

Ferguson C, Cannon DT, Wylde LA, Benson AP, Rossiter HB Power-velocity and power-efficiency implications in the limitation of ramp incremental cycle ergometry: Reply to Morales-Alamo et al. Journal of Applied Physiology 120 477-, 2016
DOI:10.1152/japplphysiol.01067.2015

Keir DA, Robertson TC, Benson AP, Rossiter HB, Kowalchuk JM The influence of metabolic and circulatory heterogeneity on the expression of pulmonary oxygen uptake kinetics in humans Experimental Physiology 101 176-192, 2016
DOI:10.1113/EP085338
View abstract

Ferguson C, Wylde LA, Benson AP, Cannon DT, Rossiter HB No reserve in isokinetic cycling power at intolerance during ramp incremental exercise in endurance-trained men Journal of Applied Physiology 120 70-77, 2016
DOI:10.1152/japplphysiol.00662.2015
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

Benson AP, Hayes-Gill B, Holden AV, Matthews R, Naz A, Page S, Pervolaraki E, Spofford E, Tayebjee M Self-terminating re-entrant cardiac arrhythmias: Quantitative characterization Computing in Cardiology 42 641-644, 2015
DOI:10.1109/CIC.2015.7410992
View abstract

Benoist D, Stones R, Benson AP, Fowler ED, Drinkhill MJ, Hardy MEL, Saint DA, Cazorla O, Bernus O, White E Systems approach to the study of stretch and arrhythmias in right ventricular failure induced in rats by monocrotaline. Prog Biophys Mol Biol 115 162-172, 2014
DOI:10.1016/j.pbiomolbio.2014.06.008
View abstract

Benson AP, Bowen TS, Ferguson C, Murgatroyd SR, Rossiter HB Optimising Oxygen Uptake Kinetic Fitting Methods in Healthy Humans Ranging in Anatomical and Physiological Characteristics, 2014

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

Atkinson AJ, Logantha SJRJ, Hao G, Yanni J, Fedorenko O, Sinha A, Gilbert SH, Benson AP, Buckley DL, Anderson RH, Boyett MR, Dobrzynski H Functional, anatomical, and molecular investigation of the cardiac conduction system and arrhythmogenic atrioventricular ring tissue in the rat heart. J Am Heart Assoc 2 e000246-, 2013
DOI:10.1161/JAHA.113.000246
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

Walton RD, Benson AP, Hardy ME, White E, Bernus O Electrophysiological and structural determinants of electrotonic modulation of repolarization by the activation sequence Frontiers in Physiology 4 1-14, 2013
DOI:10.3389/fphys.2013.00281
View abstract

Benson AP, Grassi B, Rossiter HB A validated model of oxygen uptake and circulatory dynamic interactions at exercise onset in humans Journal of Applied Physiology 115 743-755, 2013
DOI:10.1152/japplphysiol.00184.2013
View abstract

Benson AP, Bowen TS, Ferguson C, Murgatroyd SR, Rossiter HB An Algorithm To Optimise Fitting Of Phase 2 Pulmonary Oxygen Uptake Kinetics From Breath-by-Breath Measurements, 2013

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

Hoffmann U, Drescher U, Essfeld D, Benson AP, Rossiter HB Skeletal muscle {Mathematical expression} kinetics from cardio-pulmonary measurements: assessing distortions through O transport by means of stochastic work-rate signals and circulatory modelling European Journal of Applied Physiology 1-10, 2013
DOI:10.1007/s00421-013-2598-7
View abstract

Bowen TS, Rossiter HB, Benson AP, Amano T, Kondo N, Kowalchuk JM, Koga S Slowed oxygen uptake kinetics in hypoxia correlate with the transient peak and reduced spatial distribution of absolute skeletal muscle deoxygenation Experimental Physiology -, 2013
DOI:10.1113/expphysiol.2013.073270
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

Benoist D, Stones R, Drinkhill MJ, Benson AP, Yang Z, Cassan C, Gilbert SH, Saint DA, Cazorla O, Steele DS, Bernus O, White E Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension. Am J Physiol Heart Circ Physiol 302 H2381-H2395, 2012
DOI:10.1152/ajpheart.01084.2011
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

Kirk N, Benson AP, Hubbard M, Goodyer C An efficient coupled electromechanical solver for studying human re-entrant arrhythmias Computing in Cardiology 38 17-20, 2011
View abstract

Niederer SA, Kerfoot E, Benson AP, Bernabeu MO, Bernus O, Bradley C, Cherry EM, Clayton R, Fenton FH, Garny A, Heidenreich E, Land S, Maleckar M, Pathmanathan P, Plank G, Rodriguez JF, Roy I, Sachse FB, Seemann G, Skavhaug O, Smith NP Verification of cardiac tissue electrophysiology simulators using an N-version benchmark PHILOS T R SOC A 369 4331-4351, 2011
DOI:10.1098/rsta.2011.0139

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 NAB, Taggart MJ, Tong WC, Zhang H Towards a computational reconstruction of the electrodynamics of premature and full term human labour. Prog Biophys Mol Biol 107 183-192, 2011
DOI:10.1016/j.pbiomolbio.2011.07.004
View abstract

Bowen TS, Murgatroyd SR, Cannon DT, Cuff TJ, Lainey AF, Marjerrison AD, Spencer MD, Benson AP, Paterson DH, Kowalchuk JM, Rossiter HB A raised metabolic rate slows pulmonary O(2) uptake kinetics on transition to moderate-intensity exercise in humans independently of work rate. Exp Physiol 96 1049-1061, 2011
DOI:10.1113/expphysiol.2011.058321
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

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

Gilbert SH, Benson AP, Walton RD, Bernus O Slowed propagation across the compacta-trabeculata interface: a consequence of fiber and sheet anisotropy., 2011
DOI:10.1109/IEMBS.2011.6090485
View abstract

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

Aslanidi OV, Benson AP, Boyett MR, Zhang HG Mechanisms of defibrillation by standing waves in the bidomain ventricular tissue with voltage applied in an external bath PHYSICA D 238 984-991, 2009
DOI:10.1016/j.physd.2009.02.003

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

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

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, 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

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

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, 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

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

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
View abstract

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

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, 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

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

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

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

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

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

Benson AP, Holden AV Calcium oscillations and ectopic beats in virtual ventricular myocytes and tissues: Bifurcations, autorhythmicity and propagation FUNCTIONAL IMAGING AND MODELING OF HEART, PROCEEDINGS 3504 304-313, 2005

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