Interaction between spiral and paced waves in cardiac tissue

Abstract

For prevention of lethal arrhythmias, patients at risk receive implantable cardioverter-defibrillators, which use high-frequency antitachycardia pacing (ATP) to convert tachycardias to a normal rhythm. One of the suggested ATP mechanisms involves paced-induced drift of rotating waves followed by their collision with the boundary of excitable tissue. This study provides direct experimental evidence of this mechanism. In monolayers of neonatal rat cardiomyocytes in which rotating waves of activity were initiated by premature stimuli, we used the Ca(2+)-sensitive indicator fluo 4 to observe propagating wave patterns. The interaction of the spiral tip with a paced wave was then monitored at a high spatial resolution. In the course of the experiments, we observed spiral wave pinning to local heterogeneities within the myocyte layer. High-frequency pacing led, in a majority of cases, to successful termination of spiral activity. Our data show that 1) stable spiral waves in cardiac monolayers tend to be pinned to local heterogeneities or areas of altered conduction, 2) overdrive pacing can shift a rotating wave from its original site, and 3) the wave break, formed as a result of interaction between the spiral tip and a paced wave front, moves by a paced-induced drift mechanism to an area where it may become unstable or collide with a boundary. The data were complemented by numerical simulations, which was used to further analyze experimentally observed behavior.

Fig. 1

Three types of behavior observed for induced reentrant (spiral) activity. Recordings of Ca²⁺ transients are shown as relative units of fluo 4 fluorescence. Arrows indicate the application of premature stimuli, which initiated a reentrant wave. A: self-termination of a reentrant wave. B: reentrant wave termination by overdrive pacing. C: unsuccessful termination of reentrant wave activation by overdrive pacing.

Fig. 2

Endogenous heterogeneities in macroscopically homogenous coverslips. A: myocyte-free regions; B: mechanical damage due to forceps during coverslip transfer; C: areas of higher density; D: clusters of damaged cells on top of the monolayer (arrows); E: areas of lesser/uneven density.

Fig. 3

Capture of a nearby spiral by a local heterogeneity. A: 12 sequential frames show how a small area of heterogeneity, seen as a slightly brighter spot at the center, attracts the tip of a spiral wave. B: 4 sequential frames 10 cycles after the capture event shown in A. They illustrate that spiral remained stable and pinned to the same spot. Full sequence can be seen in the online supplement 1.

Fig. 4

Reentrant wave terminated by rapid pacing. A: 1 complete rotation of the reentrant wave presented as an activation map, where color indicates time of activation at each pixel. B: fluorescence snapshot of the wave. Arrow denotes direction of rotation. Normalized fluo 4 fluorescence is shown in pseudocolor. Red dot indicates position of the spiral tip. C: sequence of frames illustrating interaction of 1 paced wave front with the tip of the spiral wave before (top row) and after (bottom row) collision. Last 2 frames show formation of a wave break. ***, Site of collision. Solid lines, wave fronts; dotted lines, wave backs. Red dot indicates position of the spiral tip. D: numerical illustration of the process described in C. Dotted circle, position of a local heterogeneity [reduced time-independent K⁺ current (IK1)], around which the spiral rotates.

Fig. 5

Paced-induced drift of spiral waves. A: impeding collisions of the spiral and 4 consecutive paced waves before they reach the tip (top row) and impeding collisions of the spiral wave and 4 consecutive paced waves during the paced-induced drift (bottom row). Arrows show direction of paced wave propagation. Right: relative positions of collision site (red lines) and wave break (red circle). Dotted circle indicates location of the initial wave break; arrow shows direction of paced induced drift. At this magnification (~2 × 2 mm area), individual cell heterogeneity is clearly visible. B: graphical illustration of process shown in A. Red dots, position of wave break; black dots, collision site coordinates. Displacement was measured in the direction of drift.

Fig. 6

Paced-induced drift of spiral wave: numerical study. A: impeding collisions between the spiral wave and 4 consecutive paced waves before they reach the tip (top row) and 3 impeding collisions of the spiral wave and paced waves during paced-induced drift (bottom row). Right: relative positions of collision site (white lines) and wave break (solid circle). Dotted circle, area of local heterogeneity similar to that in Fig. 4D. B: graphical illustration of the process in A. ○, Position of the wave break; ●, collision site coordinates. *, Illustration that the wavebreak displacement occurs as a result of the previous collision (paced wave 7), and not due to the collision with what will be the next paced wave (wave 8).

Fig. 7

Paced-induced spiral wave detachment and subsequent termination due to wave break collision with a boundary. A: location of pacing electrodes and a local heterogeneity (left) and circular wave fronts of paced waves (note changes in wave curvature near local heterogeneity) and appearance of the cell layer after overdrive pacing was turned off (right). B: 4 sequential frames showing spiral wave pinned to a heterogeneity. C: 5 sequential frames showing collision of the spiral wave with the paced wave. D: 5 sequential frames showing the 2 waves coalescing into a single wave front. E: 5 sequential frames showing curling of the wave break into a new spiral wave. F: 5 sequential frames showing collapse of the wave break at the boundary. Time (in seconds) is shown in each frame.

Fig. 8

Paced-induced movements of collision and coalescence sites. A: sequential frames illustrate movement of the collision site (red bar). B: sequential frames illustrate movement of a point where the 2 waves coalesce (red triangle). Corresponding cartoons are shown at right. Time (in seconds) is shown in each frame.