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  High-Resolution Optical Measurement of Cardiac Restitution, Contraction and Fibrillation Dynamics in Beating versus Blebbistatin-uncoupled Isolated Rabbit Hearts

Kappadan, V., Telele, S., Uzelac, I., Fenton, F. H., Parlitz, U., Luther, S., et al. (2020). High-Resolution Optical Measurement of Cardiac Restitution, Contraction and Fibrillation Dynamics in Beating versus Blebbistatin-uncoupled Isolated Rabbit Hearts. Frontiers in Physiology, 11: 464. doi:10.3389/fphys.2020.00464.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-5C54-5 Version Permalink: http://hdl.handle.net/21.11116/0000-0006-A450-6
Genre: Journal Article

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 Creators:
Kappadan, Vineesh1, Author              
Telele, Saba1, Author              
Uzelac, Ilija, Author
Fenton, Flavio H., Author
Parlitz, Ulrich1, Author              
Luther, Stefan1, Author              
Christoph, Jan1, Author              
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1Research Group Biomedical Physics, Max Planck Institute for Dynamics and Self-Organization, Max Planck Society, ou_2063288              

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 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 versus Blebbistatin-arrested Langendorff-perfused rabbit hearts ($N=10$). We found action potential durations (APD) to be, on average, $25 \pm 5 \%$ 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., $9 \pm 2 Hz$ with Blebbistatin and $15 \pm 4 Hz$ without Blebbistatin ($N=10$ hearts), and maintained a broader frequency spectrum. In contracting hearts, the average number of phase singularities was $N_{PS} = 11 \pm 4$ compared to $N_{PS} = 6 \pm 3$ with Blebbistatin during VF on the anterior left 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.

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 Dates: 2020-04-162020
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.3389/fphys.2020.00464
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Title: Frontiers in Physiology
  Other : Front. Physiol.
  Abbreviation : FPHYS
Source Genre: Journal
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Publ. Info: Lausanne : Frontiers Research Foundation
Pages: 18 Volume / Issue: 11 Sequence Number: 464 Start / End Page: - Identifier: ISSN: 1664-042X
CoNE: https://pure.mpg.de/cone/journals/resource/1664-042X