High resolution optical mapping of cardiac electrophysiology in pre-clinical models

www.nature.com/scientificdata High resolution optical mapping of Data Descriptor cardiac electrophysiology in pre-clinical models OPEN Christopher O’Shea 1 ✉, James Winter1, S. Nashitha Kabir1, Molly O’Reilly1,2, Simon P Wells1,3, Olivia Baines1, Laura C. Sommerfeld1,7, Joao Correia1, Ming Lei Paulus Kirchhof1,5,7, Andrew P. Holmes1,6, Larissa Fabritz1,5,7, Kashif Rajpoot8 & Davor Pavlovic 1 4 , Optical mapping of animal models is a widely used technique in pre-clinical cardiac research. It has several advantages over other methods, including higher spatial resolution, contactless recording and direct visualisation of action potentials and calcium transients. Optical mapping enables simultaneous study of action potential and calcium transient morphology, conduction dynamics, regional heterogeneity, restitution and arrhythmogenesis. In this dataset, we have optically mapped Langendorff perfused isolated whole hearts (mouse and guinea pig) and superfused isolated atria (mouse). Raw datasets (consisting of over 400 files) can be combined with open-source software for processing and analysis. We have generated a comprehensive post-processed dataset characterising the baseline cardiac electrophysiology in these widely used pre-clinical models. This dataset also provides reference information detailing the effect of heart rate, clinically used anti-arrhythmic drugs, ischaemia-reperfusion and sympathetic nervous stimulation on cardiac electrophysiology. The effects of these interventions can be studied in a global or regional manner, enabling new insights into the prevention and initiation of arrhythmia. Background & Summary Organised depolarisation, propagation, and repolarisation of the cardiac action potential is key to coordinated contraction and relaxation of the heart. Local, regional, or global abnormalities in action potential generation, propagation and repolarisation can disturb the normal rhythm or beating rate of the heart, known as cardiac arrhythmia. Arrhythmias are common and contribute to several cardiovascular complications including sudden cardiac death, heart failure and stroke1. The mechanisms underpinning complex arrhythmias, and how to best treat these conditions, remain incompletely understood2. This has fuelled a substantial and ongoing global research effort. Cardiac optical mapping is a fluorescence-based technique which offers unparalleled spatial resolution to study the dynamics of cardiac electrophysiology3,4. Using potentiometric dyes, action potential propagation and morphology in multi-cellular cardiac preparations, including ex-vivo animal hearts, are visualised. Optical mapping has several advantages over traditional electrode measurements5. High spatial resolution enables local and/or regional alterations in cardiac electrophysiology to be observed (e.g. different chambers of the heart, apico-basal gradients)6,7. Furthermore, optical mapping enables direct contactless recording of optical action potentials, whereas multi electrode array techniques make indirect recordings of extracellular field potentials which require direct or close electrode-tissue contact8,9. By using calcium indicators, optical mapping can also 1 Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK. 2Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam UMC, location AMC, Amsterdam, The Netherlands. 3William Harvey Research Institute, Queen Mary University of London, London, UK. 4Department of Pharmacology, University of Oxford, Oxford, UK. 5Department of Cardiology, University Heart and Vascular Centre, University Medical Center Hamburg-Eppendorf, Germany and German Center for Cardiovascular Research (DZHK) partner site Hamburg/Kiel/Lubeck, Lubeck, Germany. 6Institute of Clinical Sciences, University of Birmingham, Birmingham, UK. 7 University Center of Cardiovascular Science, UKE, Hamburg, Germany. 8School of Computer Science, University of Birmingham, Birmingham, UK. ✉e-mail: Scientific Data | (2022) 9:135 | https://doi.org/10.1038/s41597-022-01253-1 1 www.nature.com/scientificdata/ www.nature.com/scientificdata be used to directly image calcium transients, the rise and fall of intracellular calcium concentration that initiates the contraction and relaxation of cardiac muscle cells10,11. These features make optical mapping an extremely powerful pre-clinical technique for studying arrhythmogenesis and the electrophysiological effects of physiological, pathophysiological, and pharmacological stimuli. Here, we provide a large database of cardiac optical mapping data from intact mouse and guinea pig whole hearts, and isolated mouse left atria. In total, 45 optical mapping datasets and over 400 individual files are provided. The dataset contains high resolution data obtained at multiple physiologically relevant pacing frequencies, both at baseline and in response to pharmacological agents (flecainide, carbenoxolone, ibutilide, cyclopiazonic acid, HMR 1556, and noradrenaline) or physiological interventions (ischaemia-reperfusion and sympathetic nervous stimulation). The data provided map cardiac electrophysiology both in sinus (intrinsic) rhythm and epicardial pacing, and during arrhythmic phenomena such as alternans and ventricular fibrillation. Due to their high spatio-temporal nature, the datasets produced by optical mapping are large and complex. The data can also be limited by poor signal quality or corruption by motion artefacts5,12. Therefore, the database described here, as well as providing an ideal tool for high-resolution regional integration of the interventions applied, will act as a resource to understanding of optical mapping data, detailed mapping analysis and potential limitations of the technique. Our group has previously designed, validated and released an open-source software ElectroMap for analysis of optical mapping13. Several other open-source tools are also available14–17, including specialised software to analyse fibrillation dynamics18 and alternans behaviour19. These tools allow effective exploration of the optical mapping data provided, without significant prior expertise. Furthermore, the database we provide represents a freely available resource for development, testing and validation of novel mapping algorithms to further improve analysis capabilities. Methods Animal welfare ethics declarations. All experiments were undertaken in accordance with ethical guide- lines set out by the United Kingdom Animals (Scientific Procedures) Act 1986 and Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes. Studies conformed to the Guide for the Care and Use of Laboratory Animals published by the U.S. National Institutes of Health under assurance number A5634-01. Studies were approved by the UK Home Office and relevant ethical committees at King’s College London (guinea pig, PPL: PF75E5F7F) and University of Birmingham (mouse, PPL: PPL 30/ (...truncated)