Luther, Stefan

[["dc.bibliographiccitation.firstpage","51"],["dc.bibliographiccitation.journal","Progress in Biophysics and Molecular Biology"],["dc.bibliographiccitation.lastpage","60"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Schlick, Susanne F."],["dc.contributor.author","Spreckelsen, Florian"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Iyer, Lavanya M."],["dc.contributor.author","Meyer, Tim"],["dc.contributor.author","Zelarayan, Laura C."],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Parlitz, Ulrich"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Rehfeldt, Florian"],["dc.date.accessioned","2020-12-10T15:20:42Z"],["dc.date.available","2020-12-10T15:20:42Z"],["dc.date.issued","2019"],["dc.description.abstract","Cardiomyocyte and stroma cell cross-talk is essential for the formation of collagen-based engineered heart muscle, including engineered human myocardium (EHM). Fibroblasts are a main component of the myocardial stroma. We hypothesize that fibroblasts, by compacting the surrounding collagen network, support the self-organization of cardiomyocytes into a functional syncytium. With a focus on early self-organization processes in EHM, we studied the molecular and biophysical adaptations mediated by defined populations of fibroblasts and embryonic stem cell-derived cardiomyocytes in a collagen type I hydrogel. After a short phase of cell-independent collagen gelation (30 min), tissue compaction was progressively mediated by fibroblasts. Fibroblast-mediated tissue stiffening was attenuated in the presence of cardiomyocytes allowing for the assembly of stably contracting, force-generating EHM within 4 weeks. Comparative RNA-sequencing data corroborated that fibroblasts are particularly sensitive to the tissue compaction process, resulting in the fast activation of transcription profiles, supporting heart muscle development and extracellular matrix synthesis. Large amplitude oscillatory shear (LAOS) measurements revealed nonlinear strain stiffening at physiological strain amplitudes (>2%), which was reduced in the presence of cells. The nonlinear stress-strain response could be characterized by a mathematical model. Collectively, our study defines the interplay between fibroblasts and cardiomyocytes during human heart muscle self-organization in vitro and underscores the relevance of fibroblasts in the biological engineering of a cardiomyogenesis-supporting viscoelastic stroma. We anticipate that the established mathematical model will facilitate future attempts to optimize EHM for in vitro (disease modelling) and in vivo applications (heart repair)."],["dc.identifier.doi","10.1016/j.pbiomolbio.2018.11.011"],["dc.identifier.pmid","30553553"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72769"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/248"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.workinggroup","RG Luther (Biomedical Physics)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY 4.0"],["dc.title","Agonistic and antagonistic roles of fibroblasts and cardiomyocytes on viscoelastic stiffening of engineered human myocardium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","063040"],["dc.bibliographiccitation.journal","New Journal of Physics"],["dc.bibliographiccitation.volume","19"],["dc.contributor.author","Stein, Sebastian"],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Parlitz, Ulrich"],["dc.date.accessioned","2018-11-07T10:22:28Z"],["dc.date.available","2018-11-07T10:22:28Z"],["dc.date.issued","2017"],["dc.description.abstract","We investigate a system of two viscoelastically coupled, modified Van der Pol oscillators to compare their synchronization properties due to elastic and viscoelastic coupling. We show that viscoelastic coupling leads to in-phase synchronization while elastic coupling favours anti-phase synchronization. To study the impact of symmetry and nonlinearity, the restoring forces in the Van der Pol oscillators are extended to include nonlinear and asymmetric components. If the asymmetry, or rather the nonlinearity, of the restoring forces exceeds a certain threshold, only in-phase synchronized motion is found to be stable. Another important finding is that chaotic solutions can only be found if the restoring forces are asymmetric and the coupling incorporates viscosity."],["dc.description.sponsorship","German Research Foundation (DFG) [SFB 937]"],["dc.identifier.doi","10.1088/1367-2630/aa6d4a"],["dc.identifier.isi","000404761900003"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14652"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42284"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Iop Publishing Ltd"],["dc.relation.haserratum","/handle/2/74922"],["dc.relation.issn","1367-2630"],["dc.relation.orgunit","Fakultät für Physik"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0/"],["dc.title","Impact of viscoelastic coupling on the synchronization of symmetric and asymmetric self-sustained oscillators"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e13449"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Physiological Reports"],["dc.bibliographiccitation.lastpage","12"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Mayer, Andreas"],["dc.contributor.author","Bittihn, Philip"],["dc.contributor.author","Luther, Stefan"],["dc.date.accessioned","2019-02-27T14:36:42Z"],["dc.date.available","2019-02-27T14:36:42Z"],["dc.date.issued","2017"],["dc.description.abstract","Spatiotemporal dynamics in cardiac tissue emerging from the coupling of individual cardiomyocytes underlie the heart's normal rhythm as well as undesired and possibly life‐threatening arrhythmias. While single cells and their transmembrane currents have been studied extensively, systematically investigating spatiotemporal dynamics is complicated by the nontrivial relationship between single‐cell and emergent tissue properties. Mathematical models have been employed to bridge this gap and contribute to a deepened understanding of the onset, development, and termination of arrhythmias. However, no such tissue‐level model currently exists for neonatal mice. Here, we build on a recent single‐cell model of neonatal mouse cardiomyocytes by Wang and Sobie (Am. J. Physiol. Heart Circ. Physiol. 294:H2565) to predict properties that are commonly used to gauge arrhythmogenicity of cardiac substrates. We modify the model to yield well‐defined behavior for common experimental protocols and construct a spatially extended version to study emergent tissue dynamics. We find a complex action potential duration (APD) restitution behavior characterized by a nonmonotonic dependence on pacing frequency. Electrotonic coupling in tissue leads not only to changes in action potential morphology but can also induce spatially concordant and discordant alternans not observed in the single‐cell model. In two‐dimensional tissue, our results show that the model supports stable functional reentry, whose frequency is in good agreement with that observed in adult mice. Our results can be used to further constrain and validate the mathematical model of neonatal mouse cardiomyocytes with future experiments."],["dc.identifier.doi","10.14814/phy2.13449"],["dc.identifier.pmid","28989116"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57649"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/186"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C03: Erholung nach Herzinsuffizienz: Analyse der transmuralen mechano-elektrischen Funktionsstörung"],["dc.relation.issn","2051-817X"],["dc.relation.workinggroup","RG Luther (Biomedical Physics)"],["dc.rights","CC BY 4.0"],["dc.title","Complex restitution behavior and reentry in a cardiac tissue model for neonatal mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2409"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","2419"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Cosi, Filippo G."],["dc.contributor.author","Giese, Wolfgang"],["dc.contributor.author","Neubert, Wilhelm"],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Chamakuri, Nagaiah"],["dc.contributor.author","Parlitz, Ulrich"],["dc.contributor.author","Falcke, Martin"],["dc.date.accessioned","2020-12-10T14:22:46Z"],["dc.date.available","2020-12-10T14:22:46Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.bpj.2019.09.023"],["dc.identifier.issn","0006-3495"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17130"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71727"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation.orgunit","Fakultät für Physik"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0/"],["dc.title","Multiscale Modeling of Dyadic Structure-Function Relation in Ventricular Cardiac Myocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","337"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.lastpage","7"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Dura, Miroslav"],["dc.contributor.author","Schröder-Schetelig, Johannes"],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.date.accessioned","2018-05-07T12:40:50Z"],["dc.date.available","2018-05-07T12:40:50Z"],["dc.date.issued","2014"],["dc.description.abstract","To investigate the dynamics and propensity for arrhythmias in intact transgenic hearts comprehensively, optical strategies for panoramic fluorescence imaging of action potential (AP) propagation are essential. In particular, mechanism-oriented molecular studies usually depend on transgenic mouse hearts of only a few millimeters in size. Furthermore, the temporal scales of the mouse heart remain a challenge for panoramic fluorescence imaging with heart rates ranging from 200 min(-1) (e.g., depressed sinus node function) to over 1200 min(-1) during fast arrhythmias. To meet these challenging demands, we and others developed physiologically relevant mouse models and characterized their hearts with planar AP mapping. Here, we summarize the progress toward panoramic fluorescence imaging and its prospects for the mouse heart. In general, several high-resolution cameras are synchronized and geometrically arranged for panoramic voltage mapping and the surface and blood vessel anatomy documented through image segmentation and heart surface reconstruction. We expect that panoramic voltage imaging will lead to novel insights about molecular arrhythmia mechanisms through quantitative strategies and organ-representative analysis of intact mouse hearts."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.3389/fphys.2014.00337"],["dc.identifier.pmid","25249982"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10964"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/14628"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.publisher","Frontiers Media S.A."],["dc.relation.doi","10.3389/fphys.2014.00337"],["dc.relation.eissn","1664-042X"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Toward panoramic in situ mapping of action potential propagation in transgenic hearts to investigate initiation and therapeutic control of arrhythmias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Kottlarz, Inga"],["dc.contributor.author","Berg, Sebastian"],["dc.contributor.author","Toscano-Tejeida, Diana"],["dc.contributor.author","Steinmann, Iris"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Wilke, Melanie"],["dc.contributor.author","Parlitz, Ulrich"],["dc.contributor.author","Schlemmer, Alexander"],["dc.date.accessioned","2021-04-14T08:29:50Z"],["dc.date.available","2021-04-14T08:29:50Z"],["dc.date.issued","2021"],["dc.description.abstract","In this study, ordinal pattern analysis and classical frequency-based EEG analysis methods are used to differentiate between EEGs of different age groups as well as individuals. As characteristic features, functional connectivity as well as single-channel measures in both the time and frequency domain are considered. We compare the separation power of each feature set after nonlinear dimensionality reduction using t-distributed stochastic neighbor embedding and demonstrate that ordinal pattern-based measures yield results comparable to frequency-based measures applied to preprocessed data, and outperform them if applied to raw data. Our analysis yields no significant differences in performance between single-channel features and functional connectivity features regarding the question of age group separation."],["dc.identifier.doi","10.3389/fphys.2020.614565"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82999"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Extracting Robust Biomarkers From Multichannel EEG Time Series Using Nonlinear Dimensionality Reduction Applied to Ordinal Pattern Statistics and Spectral Quantities"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","170024"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Royal Society Open Science"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Hornung, Daniel"],["dc.contributor.author","Biktashev, V. N."],["dc.contributor.author","Otani, N. F."],["dc.contributor.author","Shajahan, T. K."],["dc.contributor.author","Baig, T."],["dc.contributor.author","Berg, S."],["dc.contributor.author","Han, Sang Who"],["dc.contributor.author","Krinsky, V. I."],["dc.contributor.author","Luther, Stefan"],["dc.date.accessioned","2018-11-07T10:26:28Z"],["dc.date.available","2018-11-07T10:26:28Z"],["dc.date.issued","2017"],["dc.description.abstract","We propose a solution to a long-standing problem: how to terminate multiple vortices in the heart, when the locations of their cores and their critical time windows are unknown. We scan the phases of all pinned vortices in parallel with electric field pulses (E-pulses). We specify a condition on pacing parameters that guarantees termination of one vortex. For more than one vortex with significantly different frequencies, the success of scanning depends on chance, and all vortices are terminated with a success rate of less than one. We found that a similar mechanism terminates also a free (not pinned) vortex. A series of about 500 experiments with termination of ventricular fibrillation by E-pulses in pig isolated hearts is evidence that pinned vortices, hidden from direct observation, are significant in fibrillation. These results form a physical basis needed for the creation of new effective low energy defibrillation methods based on the termination of vortices underlying fibrillation."],["dc.identifier.doi","10.1098/rsos.170024"],["dc.identifier.isi","000398107700049"],["dc.identifier.pmid","28405398"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14953"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43052"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/167"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/241526/EU//EUTRIGTREAT"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C03: Erholung nach Herzinsuffizienz: Analyse der transmuralen mechano-elektrischen Funktionsstörung"],["dc.relation.issn","2054-5703"],["dc.relation.orgunit","Fakultät für Physik"],["dc.relation.workinggroup","RG Luther (Biomedical Physics)"],["dc.rights","CC BY 4.0"],["dc.title","Mechanisms of vortices termination in the cardiac muscle"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","103012"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","New Journal of Physics"],["dc.bibliographiccitation.volume","10"],["dc.contributor.affiliation","Bittihn, Philip;"],["dc.contributor.affiliation","Luther, Gisela;"],["dc.contributor.affiliation","Bodenschatz, Eberhard;"],["dc.contributor.affiliation","Krinsky, Valentin;"],["dc.contributor.affiliation","Parlitz, Ulrich;"],["dc.contributor.affiliation","Luther, Stefan;"],["dc.contributor.author","Bittihn, Philip"],["dc.contributor.author","Luther, Gisela"],["dc.contributor.author","Bodenschatz, Eberhard"],["dc.contributor.author","Krinsky, Valentin"],["dc.contributor.author","Parlitz, Ulrich"],["dc.contributor.author","Luther, Stefan"],["dc.date.accessioned","2018-11-07T11:10:06Z"],["dc.date.available","2018-11-07T11:10:06Z"],["dc.date.issued","2008"],["dc.date.updated","2022-02-09T13:17:44Z"],["dc.description.abstract","Removing anchored spirals from obstacles is an important step in terminating cardiac arrhythmia. Conventional anti-tachycardia pacing (ATP) has this ability, but only under very restrictive conditions. In a generic model of excitable media, we demonstrate that for unpinning spiral waves from obstacles this profound limitation of ATP can be overcome by far field pacing (FFP). More specifically, an argument is presented for why FFP includes and thus can only extend the capabilities of ATP in the configurations considered. By numerical simulations, we show that in the model there exists a parameter region in which unpinning is possible by FFP but not by ATP. The relevance of this result regarding clinical applications is discussed."],["dc.identifier.doi","10.1088/1367-2630/10/10/103012"],["dc.identifier.eissn","1367-2630"],["dc.identifier.fs","441448"],["dc.identifier.isi","000259958200001"],["dc.identifier.ppn","583657737"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/4322"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53145"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Iop Publishing Ltd"],["dc.relation.issn","1367-2630"],["dc.relation.orgunit","Fakultät für Physik"],["dc.rights","Goescholar"],["dc.rights.uri","https://goedoc.uni-goettingen.de/licenses"],["dc.title","Far field pacing supersedes anti-tachycardia pacing in a generic model of excitable media"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","265"],["dc.bibliographiccitation.journal","Communications in Nonlinear Science and Numerical Simulation"],["dc.bibliographiccitation.lastpage","281"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Otte, Stefan"],["dc.contributor.author","Berg, Sebastian"],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Parlitz, Ulrich"],["dc.date.accessioned","2018-11-07T10:11:26Z"],["dc.date.available","2018-11-07T10:11:26Z"],["dc.date.issued","2016"],["dc.description.abstract","The dynamics of a detailed ionic cardiac cell model proposed by Sato et al. (2009) is investigated in terms of periodic and chaotic action potentials, bifurcation scenarios, and coexistence of attractors. Starting from the model's standard parameter values bifurcation diagrams are computed to evaluate the model's robustness with respect to (small) parameter changes. While for some parameters the dynamics turns out to be practically independent from their values, even minor changes of other parameters have a very strong impact and cause qualitative changes due to bifurcations or transitions to coexisting attractors. Implications of this lack of robustness are discussed. (C) 2016 The Authors. Published by Elsevier B.V."],["dc.identifier.doi","10.1016/j.cnsns.2016.01.014"],["dc.identifier.isi","000371316800019"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14151"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40042"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/134"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C03: Erholung nach Herzinsuffizienz: Analyse der transmuralen mechano-elektrischen Funktionsstörung"],["dc.relation.issn","1878-7274"],["dc.relation.issn","1007-5704"],["dc.relation.orgunit","Fakultät für Physik"],["dc.relation.workinggroup","RG Luther (Biomedical Physics)"],["dc.rights","CC BY 4.0"],["dc.title","Bifurcations, chaos, and sensitivity to parameter variations in the Sato cardiac cell model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Kappadan, Vineesh"],["dc.contributor.author","Telele, Saba"],["dc.contributor.author","Uzelac, Ilija"],["dc.contributor.author","Fenton, Flavio"],["dc.contributor.author","Parlitz, Ulrich"],["dc.contributor.author","Luther, Stefan"],["dc.contributor.author","Christoph, Jan"],["dc.date.accessioned","2021-04-14T08:25:09Z"],["dc.date.available","2021-04-14T08:25:09Z"],["dc.date.issued","2020"],["dc.description.abstract","Optical mapping is a high-resolution fluorescence imaging technique, that uses voltage- or calcium-sensitive dyes to visualize electrical excitation waves on the heart surface. However, optical mapping is very susceptible to the motion of cardiac tissue, which results in so-called motion artifacts in the fluorescence signal. To avoid motion artifacts, contractions of the heart muscle are typically suppressed using pharmacological excitation-contraction uncoupling agents, such as Blebbistatin. The use of pharmacological agents, however, may influence cardiac electrophysiology. Recently, it has been shown that numerical motion tracking can significantly reduce motion-related artifacts in optical mapping, enabling the simultaneous optical measurement of cardiac electrophysiology and mechanics. Here, we combine ratiometric optical mapping with numerical motion tracking to further enhance the robustness and accuracy of these measurements. We evaluate the method's performance by imaging and comparing cardiac restitution and ventricular fibrillation (VF) dynamics in contracting, non-working vs. Blebbistatin-arrested Langendorff-perfused rabbit hearts (N = 10). We found action potential durations (APD) to be, on average, 25 ± 5% shorter in contracting hearts compared to hearts uncoupled with Blebbistatin. The relative shortening of the APD was found to be larger at higher frequencies. VF was found to be significantly accelerated in contracting hearts, i.e., 9 ± 2Hz with Blebbistatin and 15 ± 4Hz without Blebbistatin, and maintained a broader frequency spectrum. In contracting hearts, the average number of phase singularities was NPS = 11 ± 4 compared to NPS = 6 ± 3 with Blebbistatin during VF on the anterior ventricular surface. VF inducibility was reduced with Blebbistatin. We found the effect of Blebbistatin to be concentration-dependent and reversible by washout. Aside from the electrophysiological characterization, we also measured and analyzed cardiac motion. Our findings may have implications for the interpretation of optical mapping data, and highlight that physiological conditions, such as oxygenation and metabolic demand, must be carefully considered in ex vivo imaging experiments."],["dc.identifier.doi","10.3389/fphys.2020.00464"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81537"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","High-Resolution Optical Measurement of Cardiac Restitution, Contraction, and Fibrillation Dynamics in Beating vs. Blebbistatin-Uncoupled Isolated Rabbit Hearts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]