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Low-energy control of electrical turbulence in the heart

Nature volume 475, pages 235–239 (2011)Cite this article

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Abstract

Controlling the complex spatio-temporal dynamics underlying life-threatening cardiac arrhythmias such as fibrillation is extremely difficult, because of the nonlinear interaction of excitation waves in a heterogeneous anatomical substrate1,2,3,4. In the absence of a better strategy, strong, globally resetting electrical shocks remain the only reliable treatment for cardiac fibrillation5,6,7. Here we establish the relationship between the response of the tissue to an electric field and the spatial distribution of heterogeneities in the scale-free coronary vascular structure. We show that in response to a pulsed electric field, E, these heterogeneities serve as nucleation sites for the generation of intramural electrical waves with a source density ρ(E) and a characteristic time, τ, for tissue depolarization that obeys the power law τ ∝ Eα. These intramural wave sources permit targeting of electrical turbulence near the cores of the vortices of electrical activity that drive complex fibrillatory dynamics. We show in vitro that simultaneous and direct access to multiple vortex cores results in rapid synchronization of cardiac tissue and therefore, efficient termination of fibrillation. Using this control strategy, we demonstrate low-energy termination of fibrillation in vivo. Our results give new insights into the mechanisms and dynamics underlying the control of spatio-temporal chaos in heterogeneous excitable media and provide new research perspectives towards alternative, life-saving low-energy defibrillation techniques.

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Figure 1: Low-energy termination of cardiac electrical turbulence in vivo and in vitro.
Figure 2: Sites of activation in a cardiac preparation.
Figure 3: From anatomical structure to activation dynamics in atria (a–d) and ventricles (e–h).
Figure 4: Direct access to vortex cores.

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Acknowledgements

We thank M. L. Riccio and the Cornell University μCT Facility for Imaging and Preclinical Research for performing the micro-CT scanning, and T. K. Hitchens for technical assistance with cardiac structural imaging. M. W. Enyeart and J. Boesch assisted with the experiments and N. F. Otani provided insights from computer simulations. G. Hooker conducted the statistical analysis. This work was supported by National Science Foundation (NSF) grants 0800793 (F.H.F. and E.M.C.) and 0926190 (F.H.F.); by National Institutes of Health (NIH) grants HL075515-S04 (F.H.F.), HL075515 (R.F.G.) and HL073644 (R.F.G. and E.B.); by IFCPAR Project no. 3404-4 (A.P.); by the German Ministry for Education and Research through FKZ 01EZ0905/6 (S.L., M.Z., E.B. and G.H.); by the Kavli Institute for Theoretical Physics through NSFPHY05-51164; by the Pittsburgh Supercomputing Center (NSF TeraGrid); by the Pittsburgh NMR Center for Biomedical Research (NIH P41-EB001977); by the European Community’s Seventh Framework Programme FP7/2007–2013 agreement HEALTH-F2-2009-241526 (EUTrigTreat) and by the Max Planck Society.

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Author notes

  1. Stefan Luther and Flavio H. Fenton: These authors contributed equally to this work.

Authors and Affiliations

  1. Max Planck Institute for Dynamics and Self-Organization, Am Fassberg 17, D-37077 Göttingen, Germany

    Stefan Luther, Flavio H. Fenton, Amgad Squires, Philip Bittihn, Daniel Hornung, Elizabeth M. Cherry, Gisa Luther, Valentin I. Krinsky & Eberhard Bodenschatz

  2. Department of Biomedical Sciences, Cornell University, Ithaca, 14853, New York, USA

    Stefan Luther, Flavio H. Fenton, Elizabeth M. Cherry & Robert F. Gilmour Jr

  3. Institute for Nonlinear Dynamics, Georg August University, Am Fassberg 17, D-37077 Göttingen, Germany

    Stefan Luther, Philip Bittihn, Daniel Hornung, Gisa Luther & Eberhard Bodenschatz

  4. Heart Research Center Göttingen (HRCG), Robert-Koch-Strasse 40, D-37075 Göttingen, Germany

    Stefan Luther, Markus Zabel, Gerd Hasenfuss & Eberhard Bodenschatz

  5. Department of Clinical Sciences, Cornell University, Ithaca, 14853, New York, USA

    Bruce G. Kornreich, James Flanders, Andrea Gladuli & Luis Campoy

  6. Laboratory of Atomic and Solid State Physics, Cornell University, Ithaca, 14853, New York, USA

    Amgad Squires & Eberhard Bodenschatz

  7. Department of Cardiology and Pneumology, University Medical Center (UMG), Robert-Koch-Strasse 40, D-37075 Göttingen, Germany

    Markus Zabel & Gerd Hasenfuss

  8. School of Mathematical Sciences, Rochester Institute of Technology, Rochester, 14623, New York, USA

    Elizabeth M. Cherry

  9. Institut Non-Linéaire de Nice, F-06560 Valbonne, France

    Valentin I. Krinsky

  10. Laboratoire de Physique de l’Ecole Normale Supérieure de Lyon, Université Lyon 1 and CNRS, F-69007 Lyon, France

    Alain Pumir

  11. Department of Mechanical and Aerospace Engineering, Cornell University, Ithaca, 14853, New York, USA

    Eberhard Bodenschatz

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Contributions

E.B., F.H.F., R.F.G., V.I.K., S.L. and A.P. designed research and wrote the paper with P.B., E.M.C., G.H., D.H., B.G.K. and A.S. P.B., F.H.F., S.L. and A.S. did the in vitro experiments and analysed the data. L.C., F.H.F., J.F., R.F.G., A.G., G.H., B.G.K., S.L., A.S. and M.Z. contributed to the in vivo experiments and F.H.F. and S.L. analysed the data. P.B., F.H.F. and A.S. did the CT scanning; P.B., E.B., E.M.C., F.H.F., D.H., V.I.K., G.L., S.L., A.P. and A.S. analysed and interpreted the data.

Corresponding authors

Correspondence to Stefan Luther or Flavio H. Fenton.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Text, Supplementary Figures 1-13 with legends, Supplementary Tables 1-4 and additional references. (PDF 2300 kb)

Supplementary Movie 1

The movie shows atrial fibrillation (AF) and successful termination of AF (see Fig. 1c and e).The color indicates membrane potential (black = resting, red activated;c.f. color bar given in Fig. 1e).The times of the five AFP pulses are indicated by a red square. The field of view is 4 x 4 cm2.Note that during AFP, waves originate both from boundaries and form inside the tissue. (MOV 2760 kb)

Supplementary Movie 2

The movie shows normal sinus rhythm (see Fig. 1e).The color indicates membrane potential (black = resting, red activated;c.f. color bar given in Fig. 1e).The field of view is 4 x 4 cm^2. (MOV 687 kb)

Supplementary Movie 3

The movie shows representative examples of wave propagation in quiescent tissue induced by weak electric field pulses with E = 0.22 V/cm, E = 0.39 V/cm and E = 0.5 V/cm, respectively (pulse duration 8 ms).The color indicated time (early = red, late = blue; see Fig. 2). (MOV 285 kb)

Supplementary Movie 4

The movies (5-7) shows simulations corresponding to Figure S10, panels AD.The simulations have been done using the Barkley model.The color indicates the fast activator variable (blue = resting, red = activated).The text at the beginning of each video indicates pacing sites and relative frequencies.During the simulations, phase singularity trajectories are tracked where appropriate (indicated by white color). (MOV 1041 kb)

Supplementary Movie 5

Please read legend for Supplementary Movie 4. (MOV 5312 kb)

Supplementary Movie 6

Please read legend for Supplementary Movie 4. (MOV 5456 kb)

Supplementary Movie 7

Please read legend for Supplementary Movie 4. (MOV 1438 kb)

Supplementary Movie 8

The movie shows AF and successful termination using direct access to the core (Fig. 4e).The color indicates membrane potential (black = resting, red activated;c.f. color bar given in Fig. 4d).The times of the five AFP pulses are indicated by a red square. The field of view is 4 x 4 cm2. (MOV 2038 kb)

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Luther, S., Fenton, F., Kornreich, B. et al. Low-energy control of electrical turbulence in the heart. Nature 475, 235–239 (2011). https://doi.org/10.1038/nature10216

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