Excitation waves are known to play an important role in the self-organization of a wide variety of nonlinear media. One of the most intriguing examples of dynamic structures in excitable systems is rotating spiral waves [1-4]. Although spiral waves have been discovered in a variety of active media, their study was mostly inspired by their role in the functioning of heart in normal and pathological conditions [5-7].
Although a large amount of information about the dynamics of rotating waves has been obtained over the past three decades from experiments on model systems and computer simulations [8-16], much of this information was not sufficiently verified for real cardiac tissue. The reason was the difficulty of direct observation of the excitation wave in the real complex structure of the heart. The confirmation of accumulated theoretical and computer simulation data become more plausible with the development of an experimental model based on cultured cardiomyocyte layers [17,18].
This model enables visualization of excitation waves using potential sensitive and Ca + +-sensitive dyes, similar to experiments with real heart tissue, but has a much lower internal complexity. Furthermore, it provides a tool for creating the desired tissue structure: geometry, controlled inhomogeneity, gradients etc.
Here, we summarize our recent results in patterning cardiomyocyte tissue culture and controlling its excitability. Previously, we have shown the termination of spiral waves by pacing-induced drift and their forced collision with a boundary [19], as well as conversion of the “anatomical reentry” (pinned spiral wave) to the “functional reentry” (free rotating spiral wave) [20]. We also propose a method to control the excitability of cardiomyocyte layers by means of adding of a photo-reactive substance, azoTAB [21,22]. Although, patterned excitable tissue may be created permanently by either patterned seeding of cells or by partially removing them after attachment, it is much more challenging mission to produce excitable network with time-dependent parameters, relying on common tissue engineering methods. The digital photocontrol allows performing this task by simply changing light illumination intensity with time. We studied a process of perturbation of a stably rotating spiral wave by decreasing the excitability of the system with time. This procedure is directly related to the problem of termination of stable (functional) re-entry in the heart, as a common antiarrhythmic method. It is believed that stably rotating spiral waves in the cardiac tissue are so-called “pinned” waves, where heterogeneity in the core stabilizes the spiral wave, while unpinned, freely rotating waves are either intrinsically unstable or may migrate or drift in the naturally inhomogeneous cardiac tissue.
References
1. Gerisch, Cell aggregation and differentiation in Dictyostelium, Curr. Top. Dev. Biol. 3 (1968) 157-197.
2. A. T. Winfree, Spiral waves of chemical activity, Science, 175 (1972) 134-136.
3. M. A. Allessie, F. I. Bonke, F.J. Schopman, Circus movement in rabbit atrial muscle as a mechanism of tachycardia, Circ. Res. 33(1) (1973) 54-62.
4. K. Agladze, O. Steinbock, Waves and vortices of rust on the surface of corroding steel, J. Phys. Chem. A 104(44) (2000) 9816-9819.
5. V. Krinsky, Spread of excitation in an inhomogeneous medium (state similar to cardiac fibrillation), Biofizika 11 (1966) 776-784.
6. G. K. Moe, J. Jalife, Reentry and ectopic mechanisms in the genesis of arrhythmias, Arch. Inst. Cardiol. Mex. 47(2) (1977) 206-211.
7. A. T. Winfree, When Time Breaks Down: The Three-Dimensional Dynamics of Chemical Waves and Cardiac Arrhythmias, Princeton University Press, Princeton, NJ, 1987.
8. F. H. Fenton, E. M. Cherry, H. M. Hastings, S. J. Evans, Multiple mechanisms of spiral wave breakup in a model of cardiac electrical activity Chaos 12 (2002) 852-892.
9. E. M. Cherry, F. H. Fenton, Visualization of spiral and scroll waves in simulated and experimental cardiac tissue, New J. Phys. 10 (2008) 125016.
10. A. S. Mikhailov, K. Showalter, Control of waves, patterns and turbulence in chemical systems, Phys. Rep. 425 (2006) 79-194.
11. A. V. Panfilov, S. C. Muller, V. S. Zykov, J. P. Keener, Elimination of spiral waves in cardiac tissue by multiple electrical shocks, Phys. Rev. E, 61 (2000) 4644-4647.
12. V. Krinsky, K. Agladze, Interaction of Rotation Chemical Waves, Physica D 8 (1983) 50-56.
13. K. Agladze, J. P. Keener, S. C. Müller, A. Panfilov, Rotating spiral waves created by geometry, Science 264 (1994) 1746-1748.
14. G. Huyet, C. Dupont, T. Corriol, V. Krinsky, Unpinning of a vortex in a chemical excitable medium, Int. J. Bifurcation Chaos 8(6) (1998) 1315-1323.
15. E. A. Ermakova, V. I. Krinsky, A.V. Panfilov, A. M. Pertsov, Interaction between spiral and flat periodic autowaves in an active medium, Biofizika 31 (1986) 318-323.
16. G. Gottwald, A. Pumir, V. Krinsky, Spiral wave drift induced by stimulating wave trains, Chaos 11 (2001) 487-494.
17. V. G. Fast, R. E. Ideker, Simultaneous optical mapping of transmembrane potential and intracellular calcium in myocyte cultures, J. Cardiovasc. Electrophysiol. 11 (2000) 547-556.
18. L. Tung, J. Cysyk, Imaging fibrillation/defibrillation in a dish, J. Electrocardiology 40 (2007) S62-S65.
19. K. Agladze, M. W. Kay, V. Krinsky, N. Sarvazyan, Interaction between spiral and paced waves in cardiac tissue, Am. J. Physiol. Heart Circ. Physiol. 293 (2007) 503-513.
20. A. Isomura, M. Hörning, K. Agladze, K. Yoshikawa, Eliminating spiral waves pinned to an anatomical obstacle in cardiac myocytes by high-frequency stimuli, Phys. Rev. E 78 (2008) 066216.
21. Magome N, Kanaporis G, Moisan N, Tanaka K, Agladze K. “Photo-Control of Excitation Waves in Cardiomyocyte Tissue Culture.” Tissue Eng Part A. Volume: 17 Issue: 21-22 Pages: 2703-2711 DOI: 10.1089/ten.tea.2010.0745 Published: NOV 2011.
22. . Erofeev, IS, Magome, N, Agladze, KI "Digital photo-control of the network of live excitable cells." JETP Letters, vol. 94, issue 6, p. 477-480, 2011.