Cardiac Physiology & Biophysics
We use a combination of traditional and novel biophysical techniques to study the electrical and mechanical activity of the mammalian heart.
Staff
Publications
2024
Zervou, S., McAndrew, D. J., Lake, H. A., Kuznecova, E., Preece, C., Davies, B., Neubauer, S., Lygate, C. A. (2024) Cardiac function and energetics in mice with combined genetic augmentation of creatine and creatine kinase activity. Journal of Molecular and Cellular Cardiology, 196, pp. 105-114. (doi: 10.1016/j.yjmcc.2024.09.007)
Main, A., Mary, S., Sin, Y. Y., Wright, T. A., Ling, J., Blair, C. M., Smith, G. L., Fuller, W., Baillie, G. S. (2024) SUMOylation of cardiac myosin binding protein-C reduces its phosphorylation and results in impaired relaxation following treatment with isoprenaline. International Journal of Biochemistry and Cell Biology, 176, (doi: 10.1016/j.biocel.2024.106668)
Tabish, T. A., Hussain, M. Z., Zhu, Y., Xu, J., Huang, W. E., Diotallevi, M., Narayan, R. J., Crabtree, M. J., Khademhosseini, A., Winyard, P. G., Lygate, C. (2024) Synthesis and characterization of amine-functionalized graphene as a nitric oxide-generating coating for vascular stents. Applied Physics Reviews, 11, (doi: 10.1063/5.0192379)
Shead, K. D., Huethorst, E., Burton, F., Lang, N., Myles, R. C., Smith, G. L. (2024) Human induced pluripotent stem cell derived cardiomyocytes for pre-clinical cardiotoxicity screening. JACC: CardioOncology,
Tabish, T. A., Xu, J., Campbell, C. K., Abbas, M., Myers, W. K., Didwal, P., Carugo, D., Xie, F., Crabtree, M. J., Stride, E., Lygate, C. A. (2024) pH-sensitive release of nitric oxide gas using peptide-graphene co-assembled hybrid nanosheets. Nitric Oxide, 147, pp. 42-50. (doi: 10.1016/j.niox.2024.04.008)
Pierson, J. B., Berridge, B., Blinova, K., Brooks, M. B., Eldridge, S., O'Brien, C. E., Pugsley, M. K., Schultze, A. E., Smith, G., Stockbridge, N., Valentin, J.-P., Vicente, J. (2024) Collaborative science in action: a 20 year perspective from the Health and Environmental Sciences Institute (HESI) Cardiac Safety Committee. Journal of Pharmacological and Toxicological Methods, 127, (doi: 10.1016/j.vascn.2024.107511)
Tabish, T. A., Hussain, M. Z., Zervou, S., Myers, W. K., Tu, W., Xu, J., Beer, I., Huang, W. E., Chandrawati, R., Crabtree, M. J., Winyard, P. G., Lygate, C. A. (2024) S-nitrosocysteamine-functionalised porous graphene oxide nanosheets as nitric oxide delivery vehicles for cardiovascular applications. Redox Biology, 72, (doi: 10.1016/j.redox.2024.103144)
Loughrey, C. et al. (2024) A novel ryanodine receptor 2 inhibitor, M201-A, enhances natriuresis, renal function and lusi-inotropic action: Pre-clinical and phase I study. British Journal of Pharmacology, 181, pp. 3401-3419. (doi: 10.1111/bph.16379)
Tabish, T. A., Crabtree, M. J., Townley, H. E., Winyard, P. G., Lygate, C. A. (2024) Nitric oxide releasing nanomaterials for cardiovascular applications. JACC: Basic to Translational Science, 9, pp. 691-709. (doi: 10.1016/j.jacbts.2023.07.017)
Kemi, O. J., Hoydal, M. A., Haram, P. M., Smith, G. L., Ellingsen, O., Koch, L. G., Britton, S. L., Wisloff, U. (2024) Inherited physical capacity: Widening divergence from young to adult to old. Annals of the New York Academy of Sciences, 1534, pp. 145-155. (doi: 10.1111/nyas.15130)
Lygate, C. A. (2024) Maintaining energy provision in the heart: the creatine kinase system in ischaemia–reperfusion injury and chronic heart failure. Clinical Science, 138, pp. 491-514. (doi: 10.1042/CS20230616)
Astrauskaite, G., Mohanan, S., Williamson, L., Boland, E., Huethorst, E., Kinegawa, R., Smith, G., Muellenbroich, C. (2024) Remote Focusing for 2-photon Microscopy to Follow Action Potential Propagation Transmurally in Acute Rabbit Cardiac Slices. (doi: 10.1117/12.3002956)
Freeman, M., Huethorst, E., Boland, E., Dunne, M., Burton, F., Denning, C., Myles, R., Smith, G. (2024) A novel method for the percutaneous induction of myocardial infarction by occlusion of small coronary arteries in the rabbit. American Journal of Physiology: Heart and Circulatory Physiology, 326, pp. H735--H751. (doi: 10.1152/ajpheart.00657.2023)
Nyman, M., Stølen, T. O., Johnsen, A. B., Garten, K., Burton, F. L., Smith, G. L., Loennechen, J. P. (2024) A comprehensive protocol combining in vivo and ex vivo electrophysiological experiments in an arrhythmogenic animal model. American Journal of Physiology - Heart and Circulatory Physiology, 326, pp. H203-H215. (doi: 10.1152/ajpheart.00358.2023)
Astrauskaitė, G., Williamson, L., Mohanan, S., Moreno, S. M., Kinegawa, R., Boland, E., Huethorst, E., Smith, G., Müllenbroich, C. (2024) Fast Axial Scanning with Remote Focusing for Multiphoton Microscopy of Acute Rabbit Ventricular Slices to Follow Action Potentials Transmurally. (doi: 10.1364/CLEO_SI.2024.SF2B.1)
2023
Da Silva Costa, A., Ghouri, I., Johnston, A., Mcglynn, K., McNair, A., Bowman, P., Malik, N., Hurren, J., Bingelis, T., Dunne, M., Smith, G. L., Kemi, O. J. (2023) Electrically stimulated in vitro heart cell mimic of acute exercise reveals novel immediate cellular responses to exercise: Reduced contractility and metabolism, but maintained calcium cycling and increased myofilament calcium sensitivity. Cell Biochemistry and Function, 41, pp. 1147-1161. (doi: 10.1002/cbf.3847)
Tabish, T. A., Zhu, Y., Shukla, S., Kadian, S., Sangha, G. S., Lygate, C. A., Narayan, R. J. (2023) Graphene nanocomposites for real-time electrochemical sensing of nitric oxide in biological systems. Applied Physics Reviews, 10, (doi: 10.1063/5.0162640)
Farzi, M., Coveney, S., Afzali, M., Zdora, M.‐C., Lygate, C. A., Rau, C., Frangi, A. F., Dall'Armellina, E., Teh, I., Schneider, J. E. (2023) Measuring cardiomyocyte cellular characteristics in cardiac hypertrophy using diffusion‐weighted MRI. Magnetic Resonance in Medicine, 90, pp. 2144-2157. (doi: 10.1002/mrm.29775)
Selli, A. L., Ghasemi, M., Watters, T., Burton, F., Smith, G., Dietrichs, E. S. (2023) Proarrhythmic changes in human cardiomyocytes during hypothermia by milrinone and isoprenaline, but not levosimendan: an experimental in vitro study. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 31, (doi: 10.1186/s13049-023-01134-5)
Eisner, D., Neher, E., Taschenberger, H., Smith, G. (2023) Physiology of intracellular calcium buffering. Physiological Reviews, 103, pp. 2767-2845. (doi: 10.1152/physrev.00042.2022)
Giommi, A., Gurgel, A. R. B., Smith, G. L., Workman, A. J. (2023) Does the small conductance Ca2+-activated K+ current ISK flow under physiological conditions in rabbit and human atrial isolated cardiomyocytes? Journal of Molecular and Cellular Cardiology, 183, pp. 70-80. (doi: 10.1016/j.yjmcc.2023.09.002)
Simitev, R. D., Al dawoud, A., Aziz, M. H.N., Myles, R., Smith, G. L. (2023) Phenomenological analysis of simple ion channel block in large populations of uncoupled cardiomyocytes. Mathematical Medicine and Biology, 40, pp. 175-198. (doi: 10.1093/imammb/dqad001)
Lu, H. R., Van de Sande, D., Mohammadreza, G., Watters, T., Burton, F., Pham, L., Altrocchi, C., Gallacher, D. J., Smith, G. (2023) Are more mature hiPSC-cardiomyocytes better for the detection of drug-induced cardiotoxicity? Biomolecules, 13, (doi: 10.3390/biom13040676)
Maguire, M. L., McAndrew, D. J., Lake, H. A., Ostrowski, P. J., Zervou, S., Neubauer, S., Lygate, C. A., Schneider, J. E. (2023) Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolution 31P-CMRS in the mouse. Journal of Cardiovascular Magnetic Resonance, 25, pp. 6. (doi: 10.1186/s12968-023-00911-6)
Kuo, C.-W. S., Dobi, S., Gök, C., Da Silva Costa, A., Main, A., Robertson-Gray, O., Baptista-Hon, D., Wypijewski, K. J., Costello, H., Hales, T. G., MacQuaide, N., Smith, G. L., Fuller, W. (2023) Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes. Proceedings of the National Academy of Sciences of the United States of America, 120, (doi: 10.1073/pnas.2207887120)
McAndrew, D. J., Lake, H. A., Zervou, S., Schwedhelm, E., Schneider, J. E., Neubauer, S., Lygate, C. A. (2023) Homoarginine and creatine deficiency do not exacerbate murine ischaemic heart failure. ESC Heart Failure, 10, pp. 189-199. (doi: 10.1002/ehf2.14183)
Alexander, C., Bishop, M. J., Gilchrist, R. J., Burton, F. L., Smith, G. L., Myles, R. C. (2023) Initiation of ventricular arrhythmia in the acquired long QT syndrome. Cardiovascular Research, 119, pp. 465-476. (doi: 10.1093/cvr/cvac103)
Tabish, T. A., Lygate, C. A. (2023) Mitochondria-targeted nanomedicines for cardiovascular applications. Nanomedicine, 18, pp. 2101-2104. (doi: 10.2217/nnm-2023-0321)
2022
Saxena, P., Myles, R. C., Smith, G. L., Workman, A. J. (2022) Adrenoceptor sub-type involvement in Ca2+ current stimulation by noradrenaline in human and rabbit atrial myocytes. Pflügers Archiv European Journal of Physiology, 474, pp. 1311-1321. (doi: 10.1007/s00424-022-02746-z)
Monga, S., Valkovič, L., Tyler, D., Lygate, C. A., Rider, O., Myerson, S. G., Neubauer, S., Mahmod, M. (2022) Insights into the metabolic aspects of aortic stenosis with the use of magnetic resonance imaging. JACC: Cardiovascular Imaging, 15, pp. 2112-2126. (doi: 10.1016/j.jcmg.2022.04.025)
Lachaud, Q., Aziz, M. H. N., Burton, F. L., Macquaide, N., Myles, R. C., Simitev, R. D., Smith, G. L. (2022) Electrophysiological heterogeneity in large populations of rabbit ventricular cardiomyocytes. Cardiovascular Research, 118, pp. 3112-3125. (doi: 10.1093/cvr/cvab375)
Bruegmann, T., Smith, G. L., Lehnart, S. E. (2022) Editorial: Cardiac optogenetics: Using light to observe and excite the heart. Frontiers in Physiology, 13, (doi: 10.3389/fphys.2022.1031062)
Main, A., Bogusalvskyii, A., Howie, J., Kuo, C.-W., Rankin, A., Burton, F. L., Smith, G. L., Hajjar, R., Baillie, G. S., Campbell, K. S., Shattock, M. J., Fuller, W. (2022) Dynamic but discordant alterations in zDHHC5 expression and palmitoylation of its substrates in cardiac pathologies. Frontiers in Physiology, 13, (doi: 10.3389/fphys.2022.1023237)
Fertig, B., Ling, J., Nollet, E. E., Dobi, S., Busiau, T., Ishikawa, K., Yamada, K., Lee, A., Kho, C., Wills, L., Tibbo, A. J., Scott, M., Grant, K., Campbell, K. S., Birks, E. J., MacQuaide, N., Hajjar, R., Smith, G. L., van der Velden, J., Baillie, G. (2022) SUMOylation does not affect cardiac troponin I stability but alters indirectly the development of force in response to Ca2+ FEBS Journal, 289, pp. 6267-6285. (doi: 10.1111/febs.16537)
Nitz, K. et al. (2022) The amino acid homoarginine inhibits atherogenesis by modulating T-cell function. Circulation Research, 131, pp. 701-712. (doi: 10.1161/CIRCRESAHA.122.321094)
Lygate, C. A., Lake, H. A., McAndrew, D. J., Neubauer, S., Zervou, S. (2022) Influence of homoarginine on creatine accumulation and biosynthesis in the mouse. Frontiers in Nutrition, 9, (doi: 10.3389/fnut.2022.969702)
Malagueta-Vieira, L., Fernández-Ruocco, J., Hortigon, M., Zamora, V., Zayas-Arrabal, J., Echeazarra, L., Smith, G. L., Vila Petroff, M., Medei, E., Casis, Ó., Gallego, M. (2022) Metformin reduces potassium currents and prolongs repolarization in non-diabetic heart. International Journal of Molecular Sciences, 23, (doi: 10.3390/ijms23116021)
He, W. et al. (2022) Inhibition of myocardial cathepsin-L release during reperfusion following myocardial infarction improves cardiac function and reduces infarct size. Cardiovascular Research, 118, pp. 1535-1547. (doi: 10.1093/cvr/cvab204)
Tibbo, A. J., Mika, D., Dobi, S., Ling, J., McFall, A., Tejeda, G. S., Blair, C., MacLeod, R., MacQuaide, N., Gök, C., Fuller, W., Smith, B. O., Smith, G. L., Vandecasteele, G., Brand, T., Baillie, G. S. (2022) Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins. Journal of Molecular and Cellular Cardiology, 165, pp. 86-102. (doi: 10.1016/j.yjmcc.2022.01.001)
Dietrichs, E. S., Smith, G. L. (2022) Prediction of ventricular arrhythmias by QRS/QTc - ratio in Citalopram or Escitalopram intoxication. Frontiers in Medicine, 9, (doi: 10.3389/fmed.2022.866454)
Huethorst, E., Mortensen, P., Simitev, R. D., Gao, H., Pohjolainen, L., Talman, V., Ruskoaho, H., Burton, F. L., Gadegaard, N., Smith, G. L. (2022) Conventional rigid 2D substrates cause complex contractile signals in monolayers of human induced pluripotent stem cell derived cardiomyocytes. Journal of Physiology, 600, pp. 483-507. (doi: 10.1113/JP282228)
Faulkner-Jones, A., Zamora, V., Hortigon-Vinagre, M. P., Wang, W., Ardron, M., Smith, G. L., Shu, W. (2022) A bioprinted heart-on-a-chip with human pluripotent stem cell-derived cardiomyocytes for drug evaluation. Bioengineering, 9, (doi: 10.3390/bioengineering9010032)
2021
Farzi, M., Mcclymont, D., Whittington, H., Zdora, M.-C., Khazin, L., Lygate, C. A., Rau, C., Dall'Armellina, E., Teh, I., Schneider, J. E. (2021) Assessing myocardial microstructure with biophysical models of diffusion MRI. IEEE Transactions on Medical Imaging, 40, pp. 3775-3786. (doi: 10.1109/TMI.2021.3097907)
Müllenbroich, M. C., Kelly, A., Acker, C., Bub, G., Bruegmann, T., Di Bona, A., Entcheva, E., Ferrantini, C., Kohl, P., Lehnart, S. E., Mongillo, M., Parmeggiani, C., Richter, C., Sasse, P., Zaglia, T., Sacconi, L., Smith, G. L. (2021) Novel optics-based approaches for cardiac electrophysiology: a review. Frontiers in Physiology, 12, (doi: 10.3389/fphys.2021.769586)
Sveberg Dietrichs, E., Myles, R., Smith, G. (2021) Is hypothermia more neuroprotective than avoiding fever after cardiac arrest? Cardiovascular Research, 117, pp. e159-e161. (doi: 10.1093/cvr/cvab297)
Jabbour, R. J. et al. (2021) In vivo grafting of large engineered heart tissue patches for cardiac repair. JCI Insight, 6, (doi: 10.1172/jci.insight.144068)
Holmes, A. P., Saxena, P., Kabir, S. N., O'Shea, C., Kuhlmann, S. M., Gupta, S., Fobian, D., Apicella, C., O'Reilly, M., Syeda, F., Reyat, J. S., Smith, G. L., Workman, A. J., Pavlovic, D., Fabritz, L., Kirchhof, P. (2021) The atrial resting membrane potential confers sodium current sensitivity to propafenone, flecainide and dronedarone. Heart Rhythm, 18, pp. 1212-1220. (doi: 10.1016/j.hrthm.2021.03.016)
Bowman, P. R.T., Smith, G. L., Gould, G. W. (2021) Run for your life: can exercise be used to effectively target GLUT4 in diabetic cardiac disease? PeerJ, 9, (doi: 10.7717/peerj.11485)
Lygate, C. A. (2021) The pitfalls of in vivo cardiac physiology in genetically modified mice – lessons learnt the hard way in the creatine kinase system. Frontiers in Physiology, 12, (doi: 10.3389/fphys.2021.685064)
Zervou, S., McAndrew, D. J., Whittington, H. J., Lake, H. A., Park, K. C., Cha, K. M., Ostrowski, P. J., Eykyn, T. R., Schneider, J. E., Neubauer, S., Lygate, C. A. (2021) Subtle role for adenylate kinase 1 in maintaining normal basal contractile function and metabolism in the murine heart. Frontiers in Physiology, 12, (doi: 10.3389/fphys.2021.623969)
Carnicer, R., Duglan, D., Ziberna, K., Recalde, A., Reilly, S., Simon, J. N., Mafrici, S., Arya, R., Roselló-Lletí, E., Chuaiphichai, S., Tyler, D., Lygate, C. A., Channon, K. M., Casadei, B. (2021) BH4 increases nNOS activity and preserves left ventricular function in diabetes. Circulation Research, 128, pp. 585-601. (doi: 10.1161/CIRCRESAHA.120.316656)
Mortensen, P., Gao, H., Smith, G., Simitev, R. D. (2021) Action potential propagation and block in a model of atrial tissue with myocyte-fibroblast coupling. Mathematical Medicine and Biology, 38, pp. 106-131. (doi: 10.1093/imammb/dqaa014)
Hortigon-Vinagre, M.P., Zamora, V., Burton, F. L., Smith, G. L. (2021) The use of voltage sensitive dye di-4-ANEPPS and video-based contractility measurements to assess drug effects on excitation-contraction coupling in human induced pluripotent stem cell-derived cardiomyocytes. Journal of Cardiovascular Pharmacology, 77, pp. 280-290. (doi: 10.1097/FJC.0000000000000937)
Laasmaa, M., Branovets, J., Barsunova, K., Karro, N., Lygate, C. A., Birkedal, R., Vendelin, M. (2021) Altered calcium handling in cardiomyocytes from arginine-glycine amidinotransferase-knockout mice is rescued by creatine. American Journal of Physiology: Heart and Circulatory Physiology, 320, pp. H805-H825. (doi: 10.1152/AJPHEART.00300.2020)
Branovets, J., Karro, N., Barsunova, K., Laasmaa, M., Lygate, C. A., Vendelin, M., Birkedal, R. (2021) Cardiac expression and location of hexokinase changes in a mouse model of pure creatine deficiency. American Journal of Physiology: Heart and Circulatory Physiology, 320, pp. H613-H629. (doi: 10.1152/AJPHEART.00188.2020)
Mortensen, P., Gao, H., Smith, G., Simitev, R. D. (2021) Addendum: Action potential propagation and block in a model of atrial tissue with myocyte-fibroblast coupling. Mathematical Medicine and Biology, 38, pp. 292-298. (doi: 10.1093/imammb/dqab005)
Da Silva Costa, A., Mortensen, P., Hortigon-Vinagre, M. P., van der Heyden, M. A. G., Burton, F. L., Gao, H., Simitev, R. D., Smith, G. L. (2021) Electrophysiology of hiPSC-cardiomyocytes co-cultured with HEK cells expressing the inward rectifier channel. International Journal of Molecular Sciences, 22, (doi: 10.3390/ijms22126621)
2020
Dietrichs, E. S., McGlynn, K., Allan, A., Connolly, A., Bishop, M., Burton, F., Kettlewell, S., Myles, R., Tveita, T., Smith, G. L. (2020) Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology. Cardiovascular Research, 116, pp. 2081-2090. (doi: 10.1093/cvr/cvz309)
Salerno, S., Solvang-Garten, K., Smith, G. L., Stølen, T., Kelly, A. (2020) Two-photon excitation of FluoVolt allows improved interrogation of transmural electrophysiological function in the intact mouse heart. Progress in Biophysics and Molecular Biology, 154, pp. 11-20. (doi: 10.1016/j.pbiomolbio.2019.08.007)
Błyszczuk, P., Zuppinger, C., Costa, A., Nurzynska, D., Di Meglio, F., Stellato, M., Agarkova, I., Smith, G., Distler, O., Kania, G. (2020) Activated cardiac fibroblasts control contraction of human fibrotic cardiac microtissues by a β-adrenoreceptor-dependent mechanism. Cells, 9, (doi: 10.3390/cells9051270)
Peterzan, M. A., Clarke, W. T., Lygate, C. A., Lake, H. A., Lau, J. Y.C., Miller, J. J., Johnson, E., Rayner, J. J., Hundertmark, M. J., Sayeed, R., Petrou, M., Krasopoulos, G., Srivastava, V., Neubauer, S., Rodgers, C. T., Rider, O. J. (2020) Cardiac energetics in patients with aortic stenosis and preserved versus reduced ejection fraction. Circulation, 141, pp. 1971-1985. (doi: 10.1161/circulationaha.119.043450)
Dietrichs, E. S., Tveita, T., Myles, R., Smith, G. (2020) A novel ECG-biomarker for cardiac arrest during hypothermia. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, 28, (doi: 10.1186/s13049-020-00721-0)
Aksentijević, D., Zervou, S., Eykyn, T. R., McAndrew, D. J., Wallis, J., Schneider, J. E., Neubauer, S., Lygate, C. A. (2020) Age-dependent decline in cardiac function in Guanidinoacetate-N-methyltransferase knockout mice. Frontiers in Physiology, 10, (doi: 10.3389/fphys.2019.01535)
Cao, F., Maguire, M. L., McAndrew, D. J., Lake, H. A., Neubauer, S., Zervou, S., Schneider, J. E., Lygate, C. A. (2020) Overexpression of mitochondrial creatine kinase preserves cardiac energetics without ameliorating murine chronic heart failure. Basic Research in Cardiology, 115, (doi: 10.1007/s00395-020-0777-3)
Li, Z. et al. (2020) General principles for the validation of proarrhythmia risk prediction models: an extension of the CiPA In Silico Strategy. Clinical Pharmacology and Therapeutics, 107, pp. 102-111. (doi: 10.1002/cpt.1647)
McArthur, L., Riddell, A., Chilton, L., Smith, G. L., Nicklin, S. A. (2020) Regulation of connexin 43 by interleukin 1β in adult rat cardiac fibroblasts and effects in an adult rat cardiac myocyte: fibroblast co-culture model. Heliyon, 6, (doi: 10.1016/j.heliyon.2019.e03031)
de Korte, T., Katili, P. A., Mohd Yusof, N. A.N., van Meer, B. J., Saleem, U., Burton, F. L., Smith, G. L., Clements, P., Mummery, C. L., Eschenhagen, T., Hansen, A., Denning, C. (2020) Unlocking personalized biomedicine and drug discovery with human induced pluripotent stem cell–derived cardiomyocytes: fit for purpose or forever elusive? Annual Review of Pharmacology and Toxicology, 60, pp. 529-551. (doi: 10.1146/annurev-pharmtox-010919-023309)
2019
Gould, G., Bowman, P., Smith, G. (2019) Cardiac SNARE expression in health and disease. Frontiers in Endocrinology, 10, (doi: 10.3389/fendo.2019.00881)
Bowman, P. R.T., Smith, G. L., Gould, G. W. (2019) GLUT4 expression and glucose transport in human induced pluripotent stem cell-derived cardiomyocytes. PLoS ONE, 14, (doi: 10.1371/journal.pone.0217885)
Valli, A., Morotti, M., Zois, C. E., Albers, P. K., Soga, T., Feldinger, K., Fischer, R., Frejno, M., McIntyre, A., Bridges, E., Haider, S., Buffa, F. M., Baban, D., Rodriguez, M., Yanes, O., Whittington, H. J., Lake, H. A., Zervou, S., Lygate, C. A., Kessler, B. M., Harris, A. L. (2019) Adaptation to HIF1α deletion in hypoxic cancer cells by upregulation of GLUT14 and creatine metabolism. Molecular Cancer Research, 17, pp. 1531-1544. (doi: 10.1158/1541-7786.MCR-18-0315)
Kettlewell, S., Saxena, P., Dempster, J., Colman, M. A., Myles, R. C., Smith, G. L., Workman, A. J. (2019) Dynamic‐clamping human and rabbit atrial calcium current: narrowing ICaL window abolishes early afterdepolarisations. Journal of Physiology, 597, pp. 3619-3638. (doi: 10.1113/JP277827)
Clarke, W. T., Peterzan, M. A., Rayner, J. J., Sayeed, R. A., Petrou, M., Krasopoulos, G., Lake, H. A., Raman, B., Watson, W. D., Cox, P., Hundertmark, M. J., Apps, A. P., Lygate, C. A., Neubauer, S., Rider, O. J., Rodgers, C. T. (2019) Localized rest and stress human cardiac creatine kinase reaction kinetics at 3 T. NMR in Biomedicine, 32, (doi: 10.1002/nbm.4085)
Smith, G. L., Eisner, D. A. (2019) Calcium buffering in the heart in health and disease. Circulation, 139, pp. 2358-2371. (doi: 10.1161/circulationaha.118.039329)
Ghouri, I. A., Kelly, A., Salerno, S., Garten, K., Stølen, T., Kemi, O.-J., Smith, G. L. (2019) Corrigendum: Characterization of electrical activity in post-myocardial infarction scar tissue in rat hearts using multiphoton microscopy. Frontiers in Physiology, 10, (doi: 10.3389/fphys.2019.00364)
Dietrichs, E. S., Tveita, T., Smith, G. (2019) Hypothermia and cardiac electrophysiology: a systematic review of clinical and experimental data. Cardiovascular Research, 115, pp. 501-509. (doi: 10.1093/cvr/cvy305)
Pfeiffer-Kaushik, E. R., Smith, G. L., Cai, B., Dempsey, G. T., Hortigon-Vinagre, M. P., Zamora, V., Feng, S., Ingermanson, R., Zhu, R., Hariharan, V., Nguyen, C., Pierson, J., Gintant, G. A., Tung, L. (2019) Electrophysiological characterization of drug response in hSC-derived cardiomyocytes using voltage-sensitive optical platforms. Journal of Pharmacological and Toxicological Methods, 99, (doi: 10.1016/j.vascn.2019.106612)
2018
Lemme, M., Ulmer, B. M., Lemoine, M. D., Zech, A. T.L., Flenner, F., Ravens, U., Reichenspurner, H., Rol-Garcia, M., Smith, G., Hansen, A., Christ, T., Eschenhagen, T. (2018) Atrial-like engineered heart tissue: an in vitro model of the human atrium. Stem Cell Reports, 11, pp. 1378-1390. (doi: 10.1016/j.stemcr.2018.10.008)
Connolly, A., Kelly, A., Campos, F. O., Myles, R., Smith, G., Bishop, M. J. (2018) Ventricular endocardial tissue geometry affects stimulus threshold and effective refractory period. Biophysical Journal, 115, pp. 2486-2498. (doi: 10.1016/j.bpj.2018.11.003)
Ghouri, I. A., Kelly, A., Salerno, S., Garten, K., Stølen, T., Kemi, O.-J., Smith, G. L. (2018) Characterization of electrical activity in post-myocardial infarction scar tissue in rat hearts using multiphoton microscopy. Frontiers in Physiology, 9, (doi: 10.3389/fphys.2018.01454)
van Meer, B. J., Sala, L., Tertoolen, L. G.J., Smith, G. L., Burton, F. L., Mummery, C. L. (2018) Quantification of muscle contraction in vitro and in vivo using MUSCLEMOTION software: from stem cell-derived cardiomyocytes to zebrafish and human hearts. Current Protocols in Human Genetics, 99, (doi: 10.1002/cphg.67)
Blinova, K., Dang, Q., Millard, D., Smith, G., Pierson, J., Guo, L., Brock, M., Lu, H. R., Kraushaar, U., Zeng, H., Shi, H., Zhang, X., Sawada, K., Osada, T., Kanda, Y., Sekino, Y., Pang, L., Feaster, T. K., Kettenhofen, R., Stockbridge, N., Strauss, D. G., Gintant, G. (2018) International multisite study of human-induced pluripotent stem cell-derived cardiomyocytes for drug proarrhythmic potential assessment. Cell Reports, 24, pp. 3582-3592. (doi: 10.1016/j.celrep.2018.08.079)
Cao, F., Zervou, S., Lygate, C. A. (2018) The creatine kinase system as a therapeutic target for myocardial ischaemia–reperfusion injury. Biochemical Society Transactions, 46, pp. 1119-1127. (doi: 10.1042/BST20170504)
Stockebrand, M., Sasani, A., Das, D., Hornig, S., Hermans-Borgmeyer, I., Lake, H. A., Isbrandt, D., Lygate, C. A., Heerschap, A., Neu, A., Choe, C.-U. (2018) A mouse model of creatine transporter deficiency reveals impaired motor function and muscle energy metabolism. Frontiers in Physiology, 9, (doi: 10.3389/fphys.2018.00773)
Høydal, M. A., Kirkeby-Garstad, I., Karevold, A., Wiseth, R., Haaverstad, R., Wahba, A., Stølen, T. L., Contu, R., Ellingsen, Ø., Smith, G. L. S., Kemi, O. J., Wisløff, U. (2018) Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure. ESC Heart Failure, 5, pp. 332-342. (doi: 10.1002/ehf2.12271)
Bruegmann, T., Smith, G. L. (2018) Macrophages: new players in cardiac ageing? Cardiovascular Research, 114, pp. e47-e49. (doi: 10.1093/cvr/cvy047)
Whittington, H. J., Ostrowski, P. J., McAndrew, D. J., Cao, F., Shaw, A., Eykyn, T. R., Lake, H. A., Tyler, J., Schneider, J. E., Neubauer, S., Zervou, S., Lygate, C. A. (2018) Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia–reperfusion. Cardiovascular Research, 114, pp. 858-869. (doi: 10.1093/cvr/cvy054)
Kelly, A., Salerno, S., Connolly, A., Bishop, M., Charpentier, F., Stølen, T., Smith, G. L. (2018) Normal interventricular differences in tissue architecture underlie right ventricular susceptibility to conduction abnormalities in a mouse model of Brugada syndrome. Cardiovascular Research, 114, pp. 724-736. (doi: 10.1093/cvr/cvx244)
Boyden, P. A., Smith, G. L. (2018) Ca2+ leak, what is it? Why should we care? Can it be managed? Heart Rhythm, 15, pp. 607-614. (doi: 10.1016/j.hrthm.2017.11.018)
Malmo, V., Kelly, A., Garten, K. S., Stolen, T., Rolim, N. P. L., Wisloff, U., Smith, G., Loennechen, J. P. (2018) Aerobic interval training prevents age-dependent vulnerability to atrial fibrillation in rodents. Frontiers in Physiology, 9, (doi: 10.3389/fphys.2018.00206)
Faller, K. M. E., Atzler, D., McAndrew, D. J., Zervou, S., Whittington, H. J., Simon, J. N., Aksentijevic, D., ten Hove, M., Choe, C.-u., Isbrandt, D., Casadei, B., Schneider, J. E., Neubauer, S., Lygate, C. A. (2018) Impaired cardiac contractile function in arginine:glycine amidinotransferase knockout mice devoid of creatine is rescued by homoarginine but not creatine. Cardiovascular Research, 114, pp. 417-430. (doi: 10.1093/cvr/cvx242)
Sala, L. et al. (2018) MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo. Circulation Research, 122, pp. e5-e16. (doi: 10.1161/CIRCRESAHA.117.312067)
McCarroll, C. S. et al. (2018) Runx1 deficiency protects against adverse cardiac remodeling after myocardial infarction. Circulation, 137, pp. 57-70. (doi: 10.1161/CIRCULATIONAHA.117.028911)
Chuaiphichai, S., Rashbrook, V. S., Hale, A. B., Trelfa, L., Patel, J., McNeill, E., Lygate, C. A., Channon, K. M., Douglas, G. (2018) Endothelial cell tetrahydrobiopterin modulates sensitivity to ang (angiotensin) II–induced vascular remodeling, blood pressure, and abdominal aortic aneurysm. Hypertension, 72, pp. 128-138. (doi: 10.1161/HYPERTENSIONAHA.118.11144)
Lachaud, Q., MacQuaide, N., Burton, F., Smith, G. (2018) High-throughput study of rabbit ventricle action potential populations in MI model. Biophysical Journal, 114, pp. 625A. (doi: 10.1016/j.bpj.2017.11.3377)
2017
Lei, C. L., Wang, K., Clerx, M., Johnstone, R. H., Hortigon-Vinagre, M. P., Zamora, V., Allan, A., Smith, G. L., Gavaghan, D. J., Mirams, G. R., Polonchuk, L. (2017) Tailoring mathematical models to stem-cell derived cardiomyocyte lines can improve predictions of drug-induced changes to their electrophysiology. Frontiers in Physiology, 8, (doi: 10.3389/fphys.2017.00986)
Duncan, G., Firth, K., George, V., Hoang, M. D., Staniforth, A., Smith, G., Denning, C. (2017) Drug-mediated shortening of action potentials in LQTS2 human induced pluripotent stem cell-derived cardiomyocytes. Stem Cells and Development, 26, pp. 1695-1705. (doi: 10.1089/scd.2017.0172)
Stevens, K., Denby, L., Patel, R. K., Mark, P. B., Kettlewell, S., Smith, G. L., Clancy, M. J., Delles, C., Jardine, A. G. (2017) Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway. Nephrology Dialysis Transplantation, 32, pp. 1617-1627. (doi: 10.1093/ndt/gfw252)
Peterzan, M. A., Lygate, C. A., Neubauer, S., Rider, O. J. (2017) Metabolic remodeling in hypertrophied and failing myocardium: a review. American Journal of Physiology: Heart and Circulatory Physiology, 313, pp. H597-H616. (doi: 10.1152/ajpheart.00731.2016)
Lu, H.R., Hortigon-Vinagre, M.P., Zamora, V., Kopljar, I., De Bondt, A., Gallacher, D.J., Smith, G. (2017) Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias. Journal of Pharmacological and Toxicological Methods, 87, pp. 53-67. (doi: 10.1016/j.vascn.2017.05.001)
Saxena, P., Hortigon-Vinagre, M.P., Beyl, S., Baburin, I., Andranovits, S., Iqbal, S.M., Costa, A., IJzerman, A.P., Kügler, P., Timin, E., Smith, G.L., Hering, S. (2017) Correlation between human ether-a-go-go-related gene channel inhibition and action potential prolongation. British Journal of Pharmacology, 174, pp. 3081-3093. (doi: 10.1111/bph.13942)
Gallyas, F., Zervou, S., Whittington, H. J., Ostrowski, P. J., Cao, F., Tyler, J., Lake, H. A., Neubauer, S., Lygate, C. A. (2017) Increasing creatine kinase activity protects against hypoxia / reoxygenation injury but not against anthracycline toxicity in vitro. PLoS ONE, 12, (doi: 10.1371/journal.pone.0182994)
Lygate, C. A. (2017) Metabolic arithmetic: do two wrongs make a right? Cardiovascular Research, 113, pp. 1093-1095. (doi: 10.1093/cvr/cvx121)
Lamore, S. D., Ahlberg, E., Boyer, S., Lamb, M. L., Hortigon-Vinagre, M. P., Rodriguez, V., Smith, G. L., Sagemark, J., Carlsson, L., Bates, S. M., Choy, A. L., Stålring, J., Scott, C. W., Peters, M. F. (2017) Deconvoluting kinase inhibitor induced cardiotoxicity. Toxicological Sciences, 158, pp. 213-226. (doi: 10.1093/toxsci/kfx082)
Carnicer, R., Suffredini, S., Liu, X., Reilly, S., Simon, J. N., Surdo, N. C., Zhang, Y. H., Lygate, C. A., Channon, K. M., Casadei, B. (2017) The subcellular localization of neuronal nitric oxide synthase determines the downstream effects of NO on myocardial function. Cardiovascular Research, 113, pp. 321-331. (doi: 10.1093/cvr/cvx002)
Atzler, D., McAndrew, D. J., Cordts, K., Schneider, J. E., Zervou, S., Schwedhelm, E., Neubauer, S., Lygate, C. A. (2017) Dietary supplementation with homoarginine preserves cardiac function in a murine model of post-myocardial infarction heart failure. Circulation, 135, pp. 400-402. (doi: 10.1161/CIRCULATIONAHA.116.025673)
Smart, N., Riegler, J., Turtle, C. W., Lygate, C. A., McAndrew, D. J., Gehmlich, K., Dubé, K. N., Price, A. N., Muthurangu, V., Taylor, A. M., Lythgoe, M. F., Redwood, C., Riley, P. R. (2017) Aberrant developmental titin splicing and dysregulated sarcomere length in Thymosin β4 knockout mice. Journal of Molecular and Cellular Cardiology, 102, pp. 94-107. (doi: 10.1016/j.yjmcc.2016.10.010)
Blinova, K., Stohlman, J., Vicente, J., Chan, D., Johannesen, L., Hortigon-Vinagre, M. P., Zamora Rodriguez, V., Smith, G., Crumb, W. J., Pang, L., Lyn-Cook, B., Ross, J., Brock, M., Chvatal, S., Millard, D., Galeotti, L., Stockbridge, N., Strauss, D. G. (2017) Comprehensive translational assessment of human-induced pluripotent stem cell derived cardiomyocytes for evaluating drug-induced arrhythmias. Toxicological Sciences, 155, pp. 234-247. (doi: 10.1093/toxsci/kfw200)
2016
Fattah, C., Nather, K., McCarroll, C. S., Hortigon-Vinagre, M. P., Zamora Rodriguez, V., Flores-Munoz, M., McArthur, L., Zentilin, L., Giacca, M., Touyz, R. M., Smith, G. L., Loughrey, C. M., Nicklin, S. A. (2016) Gene therapy with Angiotensin-(1-9) preserves left ventricular systolic function after myocardial infarction. Journal of the American College of Cardiology, 68, pp. 2652-2666. (doi: 10.1016/j.jacc.2016.09.946)
Huethorst, E., Hortigon, M., Zamora-Rodriguez, V., Reynolds, P.M., Burton, F., Smith, G., Gadegaard, N. (2016) Enhanced human-induced pluripotent stem cell derived cardiomyocyte maturation using a dual microgradient substrate. ACS Biomaterials Science and Engineering, 2, pp. 2231-2239. (doi: 10.1021/acsbiomaterials.6b00426)
Teh, I., McClymont, D., Zdora, M.-C., Whittington, H. J., Davidoiu, V., Lee, J., Lygate, C. A., Rau, C., Zanette, I., Schneider, J. E. (2016) Validation of diffusion tensor MRI measurements of cardiac microstructure with structure tensor synchrotron radiation imaging. Journal of Cardiovascular Magnetic Resonance, 19, (doi: 10.1186/s12968-017-0342-x)
Zak, J. et al. (2016) ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome. Cell Death and Differentiation, 23, pp. 1973-1984. (doi: 10.1038/cdd.2016.76)
Hortigon-Vinagre, M.P., Zamora, V., Burton, F.L., Green, J., Gintant, G.A., Smith, G.L. (2016) The use of ratiometric fluorescence measurements of the voltage sensitive dye Di-4-ANEPPS to examine action potential characteristics and drug effects on human induced pluripotent stem cell-derived cardiomyocytes. Toxicological Sciences, 154, pp. 320-331. (doi: 10.1093/toxsci/kfw171)
Weinberger, F., Breckwoldt, K., Pecha, S., Kelly, A., Geertz, B., Starbatty, J., Yorgan, T., Cheng, K.-H., Lessmann, K., Stolen, T., Scherrer-Crosbie, M., Smith, G., Reichenspurner, H., Hansen, A., Eschenhagen, T. (2016) Cardiac repair in guinea pigs with human engineered heart tissue from induced pluripotent stem cells. Science Translational Medicine, 8, pp. 363ra148-363ra148. (doi: 10.1126/scitranslmed.aaf8781)
Crocini, C., Ferrantini, C., Coppini, R., Scardigli, M., Yan, P., Loew, L. M., Smith, G., Cerbai, E., Poggesi, C., Pavone, F. S., Sacconi, L. (2016) Optogenetics design of mechanistically-based stimulation patterns for cardiac defibrillation. Scientific Reports, 6, (doi: 10.1038/srep35628)
Teh, I., McClymont, D., Burton, R. A. B., Maguire, M. L., Whittington, H. J., Lygate, C. A., Kohl, P., Schneider, J. E. (2016) Resolving fine cardiac structures in rats with high-resolution diffusion tensor imaging. Scientific Reports, 6, (doi: 10.1038/srep30573)
Høydal, M. A., Stølen, T. O., Kettlewell, S., Maier, L. S., Brown, J. H., Sowa, T., Catalucc, D., Condorelli, G., Kemi, O. J., Smith, G. L., Wisløff, U. (2016) Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+-homeostasis. Journal of Applied Physiology, 121, pp. 212-220. (doi: 10.1152/japplphysiol.00188.2016)
Baumert, M., Porta, A., Vos, M. A., Malik, M., Couderc, J.-P., Laguna, P., Piccirillo, G., Smith, G. L., Tereshchenko, L. G., Volders, P. G.A. (2016) QT interval variability in body surface ECG: measurement, physiological basis, and clinical value: position statement and consensus guidance endorsed by the European Heart Rhythm Association jointly with the ESC Working Group on Cardiac Cellular Electrophysiology. Europace, 18, pp. 925-944. (doi: 10.1093/europace/euv405)
Nisbet, A. M., Camelliti, P., Walker, N. L., Burton, F. L., Cobbe, S. M., Kohl, P., Smith, G. L. (2016) Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: role of fibrosis and connexin remodelling. Journal of Molecular and Cellular Cardiology, 94, pp. 54-64. (doi: 10.1016/j.yjmcc.2016.03.011)
Bertrand, L., Whittington, H. J., McAndrew, D. J., Cross, R. L., Neubauer, S., Lygate, C. A. (2016) Protective effect of creatine elevation against ischaemia reperfusion injury is retained in the presence of co-morbidities and during cardioplegia. PLoS ONE, 11, (doi: 10.1371/journal.pone.0146429)
Zervou, S., Whittington, H. J., Russell, A. J., Lygate, C. A. (2016) Augmentation of creatine in the heart. Mini-Reviews in Medicinal Chemistry, 16, pp. 19-28. (doi: 10.2174/1389557515666150722102151)
Lygate, C. A. (2016) Energetics in the hypertrophied and failing heart. Elsevier (Academic Press)
Zervou, S., Yin, X., Nabeebaccus, A. A., O’Brien, B. A., Cross, R. L., McAndrew, D. J., Atkinson, R. A., Eykyn, T. R., Mayr, M., Neubauer, S., Lygate, C. A. (2016) Proteomic and metabolomic changes driven by elevating myocardial creatine suggest novel metabolic feedback mechanisms. Amino Acids, 48, pp. 1969-1981. (doi: 10.1007/s00726-016-2236-x)
2015
Rog-Zielinska, E.A., Craig, M.-A., Manning, J.R., Richardson, R.V., Gowans, G.J., Dunbar, D.R., Gharbi, K., Kenyon, C.J., Holmes, M.C., Hardie, D.G., Smith, G.L., Chapman, K.E. (2015) Glucocorticoids promote structural and functional maturation of foetal cardiomyocytes: a role for PGC-1α. Cell Death and Differentiation, 22, pp. 1106-1116. (doi: 10.1038/cdd.2014.181)
McArthur, L., Chilton, L., Smith, G. L., Nicklin, S. A. (2015) Electrical consequences of cardiac myocyte: fibroblast coupling. Biochemical Society Transactions, 43, pp. 513-518. (doi: 10.1042/BST20150035)
Ruparelia, N., Godec, J., Lee, R., Chai, J. T., Dall'Armellina, E., McAndrew, D., Digby, J. E., Forfar, J. C., Prendergast, B. D., Kharbanda, R. K., Banning, A. P., Neubauer, S., Lygate, C. A., Channon, K. M., Haining, N. W., Choudhury, R. P. (2015) Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans. European Heart Journal, 36, pp. 1923-1934. (doi: 10.1093/eurheartj/ehv195)
Smith, G. L., MacQuaide, N. (2015) The direct actions of flecainide on the human cardiac ryanodine receptor: keeping open the debate on the mechanism of action of local anesthetics in CPVT. Circulation Research, 116, pp. 1284-1286. (doi: 10.1161/CIRCRESAHA.115.306298)
Douglas, G., Hale, A. B., Crabtree, M. J., Ryan, B. J., Hansler, A., Watschinger, K., Gross, S. S., Lygate, C. A., Alp, N. J., Channon, K. M. (2015) A requirement for Gch1 and tetrahydrobiopterin in embryonic development. Developmental Biology, 399, pp. 129-138. (doi: 10.1016/j.ydbio.2014.12.025)
Faller, K. M.E., McAndrew, D. J., Schneider, J. E., Lygate, C. A. (2015) Refinement of analgesia following thoracotomy and experimental myocardial infarction using the Mouse Grimace Scale. Experimental Physiology, 100, pp. 164-172. (doi: 10.1113/expphysiol.2014.083139)
Maguire, M. L., Geethanath, S., Lygate, C. A., Kodibagkar, V. D., Schneider, J. E. (2015) Compressed sensing to accelerate magnetic resonance spectroscopic imaging: evaluation and application to 23Na-imaging of mouse hearts. Journal of Cardiovascular Magnetic Resonance, 17, (doi: 10.1186/s12968-015-0149-6)
Ghouri, I. A., Kelly, A., Burton, F. L., Smith, G. L., Kemi, O. J. (2015) 2-photon excitation fluorescence microscopy enables deeper high-resolution imaging of voltage and Ca2+in intact mice, rat, and rabbit hearts. Journal of Biophotonics, 8, pp. 112-123. (doi: 10.1002/jbio.201300109)
MacCannell, K.A., Chilton, L., Smith, G.L., Giles, W.R. (2015) Mathematical simulations of sphingosine-1-phosphate actions on mammalian ventricular myofibroblasts and myocytes. Springer
Our research spans the colleges of MVLS and Science and Engineering. Our researchers are specialized in clinical science (cardiology), preclinical sciences (physiology/pharmacology/biochemistry/engineering), and chemistry, physics/mathematics. All members have an interest in developing novel approaches to address key questions on cardiac function. Examples of specific areas of study are:
- Optical techniques to assess cardiac electrophysiology, intracellular calcium and contractility; these include wide field imaging, confocal and multiphoton microscopy and photometry to assess multicellular and single cell electrophysiology
- Novel methods in current and voltage clamp techniques applied to single cells and multicellular systems
- Motion analysis, echocardiography and MRI images to assess mechanical function and structure
- Development of novel substrates for cell support and monitoring cardiac preparations
- Mathematical techniques to (i) model electrical and mechanical properties of the heart (ii) to analyze and extract biophysical information from the electrical and mechanical signals that reflect normal and abnormal cardiac physiology.
The group supports work on a range of small animal models of cardiac dysfunction as well as techniques and protocols to study the human heart both in vivo and in vitro. We use a range of techniques to isolate viable tissue from biopsy and autopsy samples to allow a detailed understanding of physiology of human atrial and ventricular tissue. These techniques allow the group to further our understanding of normal cardiac physiology and biophysics. This links to mechanistic work in arrhythmias (both atrial and ventricular) and mechanical dysfunction associated with heart failure.