Common mechanism links spiral wave meandering and wave-front–obstacle separation

J. M. Starobin* and C. F. Starmer Departments of Medicine (Cardiology) and Computer Science, Duke University Medical Center, P.O. Box 3181, Durham, North Carolina 27710 ͑Received 6 May 1996; revised manuscript received 30 September 1996͒ Spiral waves rotate either around a circular core or , inscribing a noncircular . The medium properties determining the transition of meandering were found to be equivalent to those defining the transition from wave tip separation and attachment around the end of an unexcitable strip of thickness comparable to zero velocity wave-front thickness. The transition from circular to noncircular tip movement is analytically pre- dicted by the balance of the diffusive fluxes within the boundary layer at the wave tip. ͓S1063-651X͑97͒11701-9͔

PACS number͑s͒: 47.32.Cc, 82.40.Ϫg

Spiral waves appear in many excitable chemical and bio- ciated with the transition between wave-front–obstacle at- logical media ͓1͔. The spiral wave tip either rotates around a tachment and separation following a wave-obstacle interac- circular unexcited core or , inscribing a noncircular tion ͓Fig. 1͑a͔͒. We found that the minimal that the pattern often similar to that of a multipetal flower. From spiral wave tip can approach its refractory tail without me- numerical studies of FitzHugh-Nagumo-like models for a va- andering is of the order of Lcrit , the wave-front thickness of riety of medium parameters, Zykov ͓2͔ and Winfree ͓3͔ a wave propagating with zero velocity. Following interaction found a distinct boundary separating meandering from circu- with an unexcitable strip of thickness Lcrit , there are two lar tip movement, suggesting that transitions between differ- possible outcomes. If the wave tip wraps itself around the ent modes of tip movement were dependent on certain me- end of this unexcitable strip, then it will meander if the strip dium parameter values. is removed. Alternatively, if the wave tip separates from the The transition from circular spiral tip to meander- end of the strip, then removal will result in circular spiral tip ing is known to occur when the spiral tip approaches its motion. Over a range of medium parameters, this transition refractory tail. The minimal distance between the spiral tip can be accurately predicted by approximating the diffusive and refractory tail associated with the meandering transition fluxes within the boundary layer at the wave tip ͓9,10͔. and its relation to medium properties, though, is uncertain. Here we consider nonlinear reaction-diffusion equations Recently numerical studies of Karma ͓4͔ showed that mean- of the FitzHugh-Nagumo class: dering corresponds to the superposition of two rotating spiral 2uץ 2uץ uץ wave solutions. He found that the reaction-diffusion field at points located on the wave front near the minimal core radius ϭ ϩ ϩ f ͑u͒ϪV, ͑1͒ t x2 y 2 ץ ץ ץ -associated with the meandering transition ͑determined nu merically͒ displayed quasiperiodic variations originating Vץ -from a supercritical Hopf bifurcation. Analytical investiga tions of spiral core stability by Kessler et al. ͓5͔ based on ϭ␧͑␥uϪV͒, ͑2͒ tץ kinematic theory did not confirm this behavior, probably be- cause their analysis was performed within a kinematic frame- work that differed significantly from the framework of Kar- where u(x,y,t) is a dimensionless similar to the ma’s analysis ͓4͔. Moreover, the kinematic approach is transmembrane potential in a biological excitable cell and limited by the assumption that the wave radius of curvature V(x,y,t) is a dimensionless function similar to a slower re- is large compared with the , a condition that is covery current. Using this electrical analogy, we consider not fulfilled at the spiral tip ͓6͔. Barkley developed a phe- reaction-diffusion fluxes to be the flow of a charge ͑current͒ nomenological model that reproduced complex spiral tip down a potential gradient. The nonlinear source of charge is movement ͓7͔. However, based on the ordinary differential determined by the function, f (u), that represents the reactive equation representation, this model did not describe the tran- properties of the medium. We consider f (u) as a piecewise sition to meandering and did not provide a minimal core linear function similar to the current-voltage relationship of a radius associated with a meandering transition boundary nonlinear oscillator ͓Fig. 1͑b͔͒. The slope of this function, ␭, since it neglected generic diffusive properties of an excitable controls one aspect of excitability by determining the maxi- medium. mum current that is available to excite adjoining regions of In this paper, we show that the conditions associated with the medium: larger values of ␭ result in a more excitable the meandering transition are equivalent to conditions asso- medium while smaller values of ␭ result in a less excitable medium. Excitability is also influenced by m1 , m2, and m3, the zeros of f (u) with respect to the equilibrium value of *Author to whom correspondence should be addressed. Fax: the recovery variable, Veq . A highly excitable medium is ͑919͒684-8666. Electronic address: josefhodgkin.mc.duke.edu determined by m2Ϫm1Ӷm3Ϫm2. The factors ␥ and ␧͑the

1063-651X/97/55͑1͒/1193͑4͒/$10.0055 1193 © 1997 The American Physical Society 1194 BRIEF REPORTS 55

FIG. 2. Shown are four spirals of increasing wave-front charge as defined by the slope of the fast null-cline ␭. Spiral waves were computed for ␧ϭ0.018, ␣ϭ2.75, and ␥ϭ7 while varying ␭ and were initiated by a wave break created with the initial conditions. The spiral tip was tracked by following the path of the unstable point uϭm2 , VϭVeqϭ0. Upper panels ͑left, ␭ϭ0.86 and right, ␭ϭ0.885͒ show circular spiral tip movement. When ␭ϭ0.905, the wave-front thickness is comparable to the core diameter and the tip begins to meander ͑low left panel͒. When ␭ is further increased to FIG. 1. ͑a͒ shows the computed temporal sequence ͑from left to 0.93, meandering becomes very pronounced ͑low right panel͒. right͒ of wave-front–obstacle interaction resulting in separation of the excitation wave from the unexcitable obstacle. The left frame demonstrates a fully formed spiral tip, which later separates from the strip ͑right frame͒. The width of the strip is of the order of the critical wave-front thickness shown in both fragments by a thin white line bounding the tip area. Computations were performed over a 170ϫ170 grid using an implicit fractional-step method ͓8͔ with ⌬xϭ⌬yϭ0.25, ⌬tϭ0.2. ͑b͒ shows the null-clines of the re- action diffusion system of Eqs. ͑1͒ and ͑2͒. We consider u(x,y,t)as similar to the transmembrane potential of an excitable cardiac or nerve cell, f (u) is similar to the current-voltage relationship of the cellular excitation process, and V(x,y,t) is similar to slow recovery current. The function f (u) is a piecewise linear function, where the slope of each linear element, ␭, refers to the rate of the fast excita- tion process and influences medium excitability. The slope ␥ refers to the rate of the slow recovery process. For a 1D excitable cable and piecewise linear f (u) the basic characteristics of wave propa- gation such as pulse propagation velocity, wave-front thickness, and the minimal wave-front thickness Lcrit associated with a nonpropa- gating wave have been determined in ͓9,10͔. ratio of fast to slow time constants͒, are relaxation param- FIG. 3. Shown is the meandering transition coinciding with the eters and ␧Ӷ1[␣ϭ(m Ϫm )/(m Ϫm )]. 3 2 2 1 wave-front–obstacle separation-attachment boundary. Spiral waves In order to explore the hypothesis that no separation from were computed for ␧ϭ0.018, ␣ϭ2.75, and ␥ϭ7 while varying ␭. the obstacle is equivalent to meandering, we observed Upper panels, ␭ϭ0.93 ͑from left to right͒, demonstrate the excita- obstacle-wave interactions for a variety of model parameters, tion wave tip, which wraps around the unexcitable strip ͑left upper ␭, ␣, and ␧, in order to alter the wave-front charge while panel͒ approaching the refractory tail. This wave fragment mean- keeping the kinetics of recovery constant. We observed the ders after obstacle removal ͑right upper panel͒. The width of the transition from circular to noncircular tip movement as fol- striplike obstacle ͑thin straight white line͒ is of the order of the lows ͑Fig. 2͒: starting with a spiral rotating around a large wave-front thickness ͑white thin layer bounding the wave tip͒.As core ͑left upper panel͒, as we increased the wave-front we decreased the wave-front charge by decreasing ␭͑␭ϭ0.86͒ the charge ͑by increasing ␭͒, the spiral tip rotated about circular wave tip separated from the obstacle ͑lower left panel͒. This wave cores of progressively smaller radii ͑right upper panel͒ until fragment rotated around a small unexcited circular core after ob- the tip approached the refractory tail by a critical distance. stacle removal ͑low right panel͒. 55 BRIEF REPORTS 1195

FIG. 4. The coincidence of the meandering transition with the FIG. 5. The boundary defining the theoretical transitions be- wave-front–obstacle separation-attachment boundary ͑a͒ in the ͑␧, tween circular and noncircular tip motion. ͑a͒ illustrates qualitative ␣͒ plane for ␭ϭ0.67 and ␥ϭ6. Squares illustrate the computed me- agreement of Eq. ͑3͒͑in a wide range of ␣͒ with the multivalued andering transition while circles refer to a computed wave-front– meandering transition in the ͑␧,␣͒ plane ͑␥ϭ6, ␭ϭ0.5͒ as described obstacle separation-attachment boundary ͑solid line is a quadratic in ͓2,6͔. ͑b͒ illustrates quantitative agreement within the range of regression: ␧ϭ0.028Ϫ0.03␣ϩ0.0087␣2). Computations were per- ␣ϭ͑2.8, 3.0͒. The solid line is the analytical estimation of the me- formed for the striplike unexcitable obstacles with the width that is andering transition boundary determined by Eq. ͑3͒ and the circles of the order of the wave-front thickness ͓see Fig. 1͑a͔͒. ͑b͒ illus- refer to numeric estimates. trates the ‘‘flower garden’’ ͑tip trajectories͒ for points indicated in

͑a͒ by numbers 1,2,3,4,5 for ␣ϭ2.3; ␧ϭ0.032, 0.048, 0.057, 0.065, ϾLcrit after the strip is removed from the medium ͑low right 0.075 and numbers 6,7,8,9,10 for ␣ϭ3.0; ␧ϭ0.01, 0.0117, 0.0129, panel͒. 0.0157, 0.0175, respectively. Numerical studies demonstrated the equivalence between conditions for the wave-front–obstacle attachment- When the distance was less than this critical distance, the tip separation boundary and the boundary of the transition to meandered ͑low panels left and right, respectively͒. meandering in the ͑␧, ␣͒ plane ͓Fig. 4͑a͔͒ over a wide range In our numerical experiments the critical distance be- of medium parameters. Moreover, small changes in the pa- tween the spiral tip and a refractory tail associated with the rameter ␧ near the transition boundary resulted in a variety of meandering transition was always comparable to that of the flower configurations quite similar to those associated with zero velocity wave-front thickness, Lcrit . Figure 3 demon- the cubic f (u) ͓2,3,7͔ as shown in Fig. 4͑b͒. strates that if the tip approaches the refractory tail within a The coincidence between the meandering transition and distance that is of the order of Lcrit ͑thin white strip between obstacle attachment-separation transition suggests a common the tip and the refractory tail͒, i.e., the tip is able to make a mechanism for both transition processes, which is based on turn of diameter, Lcrit , while maintaining attachment to the the balance of reaction-diffusion fluxes within a small strip boundary ͑upper left panel͒ then meandering results af- boundary layer of the order of the zero velocity wave-front ter removal of the strip ͑upper right panel͒. Similarly, if the thickness, Lcrit . Recently we showed that by discretizing this charge available in the wave front is insufficient to extend boundary layer with squares of the order of the zero velocity the tip around the corner of the strip ͑low left panel, lower wave-front thickness, Lcrit , it was possible to develop an excitability, ␭͒ then the wave tip cannot approach the refrac- analytical approximation of the separation–no separation tory tail sufficiently close. Consequently, the tip will rotate boundary ͓10͔. Whether the wave tip maintained the attach- around a small circular unexcited core with a diameter ment or separated from the obstacle boundary depended on 1196 BRIEF REPORTS 55 what we called a charge balance CB , derived from the inte- the end of an unexcitable strip of the order of the wave-front gral form of the Eqs. ͑1͒ and ͑2͒ obtained by averaging them thickness͒, then it will meander if the strip is removed. Thus, within a piecewise rectangular approximation of the bound- we demonstrate that the transition from circular to noncircu- ary layer over the wave-front formation time. CB was de- lar spiral tip motion is determined by the same conditions for fined in terms of a relationship between the charge available the transition from wave tip separation to attachment of the within the wave front, the charge required to ignite the wave to the end of a thin ͑of the order of the zero velocity boundary layer, and the charge that leaks from the boundary wave-front thickness͒ unexcitable strip and can be predicted from the medium properties by analysis of the boundary layer into adjacent rested medium. When CBϾ0, wave- layer separating the spiral wave tip from the ‘‘virtual’’ ob- front–obstacle attachment was maintained while when CB Ͻ0, wave-front–obstacle separation occurred. For a striplike stacle ͓9,10͔. obstacle one can find the medium parameters associated with Spiral core stability studies based on the analysis of tem- the wave-front–obstacle separation-attachment boundary poral flux variations at fixed points ͑along the spiral core boundary͒ demonstrated unstable oscillating behavior at the from the equation CBϭ0, which is given by spiral core ͓4,5͔. However, these analyses yielded little in- 47 ␣ϩ1 4͑␣ϩ1͒3 4␥͑␣ϩ1͒5␴ sight about the medium conditions associated with the me- 33Ϫ ␭3ϩ ␭2Ϫ␧ ϭ0, ͫ 2␴2 ␣Ϫ1ͬ ␣͑␣Ϫ1͒ ␣2͑␣Ϫ1͒ andering transition and the minimal core radius ͑associated ͑3͒ with meandering transition͒ which are determined by a full solution of the original partial differential equation reaction- diffusion system. By approximating the solution of the where ␴ϭ1ϩln2, ␣ϭ(m Ϫm )/(m Ϫm ) ͓10͔. Our nu- 3 2 2 1 FitzHugh-Nagumo reaction-diffusion system Eqs. ͑1͒ and ͑2͒ merical studies show that the same analysis can be applied to in the region of the spiral tip, we have shown that the deli- the transition between circular and noncircular tip motion. cate balance between reaction-diffusion fluxes in this region When C Ͻ0, circular motion is expected. When C Ͼ0 me- B B and the surrounding boundary layer plays a major role in andering is expected. defining different types of spiral tip motion, thus affecting Equation ͑3͒ is in qualitative agreement with the multival- different instabilities of the spiral wave solution at points ued meandering transition in the ͑␧, ␣͒ plane shown in near the wave tip as described in ͓4,5͔. Recognizing that ͓2,3,7͔͓Fig. 5͑a͔͒. Comparison of numerical estimates of the small changes in the reaction-diffusion flux balance in the meandering–no-meandering boundary and theoretical pre- boundary layer can dramatically alter spiral tip motion pro- dictions of the wave-front–obstacle separation-attachment vides a new tool for control of spiral wave processes and, in boundary ͓Eq. ͑3͔͒ over a limited range of ␣ reveals good particular, control of cardiac arrhythmias. quantitative agreement ͓Fig. 5͑b͔͒. Numerical estimates out- side this range are limited by the series approximation used We wish to acknowledge the critical assistance provided in deriving Eq. ͑3͓͒10͔. by V. N. Polotsky. His discussions were helpful in clarifying In summary, we determined the minimal distance between our results. This research was supported in part by Grant No. a spiral wave tip and its refractory tail associated with the HL32994 from the National Heart, Lung, and Blood Insti- meandering transition. We have found that if the wave tip tute, National Institutes of Health and a grant from the Whi- approached its tail within a distance Lcrit ͑wraps itself around taker Foundation.

͓1͔ A. T. Winfree, When Time Breaks Down: The Three- Active Systems ͑Springer, Berlin, 1990͒. Dimensional Dynamics of Electrochemical Waves and Cardiac ͓7͔ D. Barkley and I. G. Kevrekidis, Chaos 4, 453 ͑1994͒. Arrhythmias ͑Princeton Univ. Press, Princeton, 1987͒. ͓8͔ R. D. Richtmayer, Difference Methods for Initial-Value Prob- ͓2͔ V. S. Zykov, Biofizika 31, 862 ͑1986͒. lems ͑Interscience, New York, 1957͒. ͓3͔ A. T. Winfree, Chaos 1, 303 ͑1991͒. ͓9͔ J. M. Starobin, Y. I. Zilberter, and C. F. Starmer, Physica ͓4͔ A. Karma, Phys. Rev. Lett. 65, 2824 ͑1990͒. ͑Amsterdam͒ 70D, 321 ͑1994͒. ͓5͔ D. A. Kessler, H. Levine, and W. Reynolds, Phys. Rev. Lett. ͓10͔ J. M. Starobin and C. F. Starmer, Phys. Rev. E 54, 430 ͑1996͒; 68, 401 ͑1992͒; Physica ͑Amsterdam͒ 70D, 115 ͑1994͒. J. M. Starobin, Y. I. Zilberter, E. M. Rusnak, and C. F. ͓6͔ A. S. Mikhailov, Foundations of Synergetics 1. Distributed Starmer, Biophys. J 70, 581 ͑1996͒.