Eight (or more) kinds of alternans - PubMed (original) (raw)

Eight (or more) kinds of alternans

Alan Garfinkel. J Electrocardiol. 2007 Nov-Dec.

Abstract

Cardiac electrical alternans is an alternating rhythm in the electrical properties of the heart, such as cellular action potential duration, conduction velocity, and/or intracellular calcium (Ca) concentrations. These alternations can initiate reentrant arrhythmias and can also break up ongoing reentry, creating ventricular fibrillation. Alternans can take several forms. The alternation in time can be uniform in space (concordant alternans) or can have regions that are out of phase with other regions (discordant alternans). Alternans can be driven by voltage instabilities (involving electrical restitution) or by Ca instabilities. In addition, the relation between voltage and Ca can be positive or negative. Anatomical factors can play a role in generating spatially discordant alternans, but there is also a critical role for instabilities that are dynamically generated and can only be understood as the response of a nonlinear medium to periodic excitation. This is especially true of spatially discordant alternans, the most deadly form. We will review the role of factors such as action potential duration, conduction velocity, and Ca, which interact with each other to produce alternans. Simulations of cardiac conduction support these conclusions, as do experiments in a variety of animal and human preparations.

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Figures

Fig. 1

Fig. 1

Alternans in ECG in guinea pig heart (upper tracing) and in 2 local action potential sites (as recorded by V-sensitive dyes; reproduced with permission from Pastore et al2).

Fig. 2

Fig. 2

Left panels, When a rabbit myocyte is paced at 180 milliseconds, membrane Vand intracellular Ca both alternate; VAPDs alternate long-short, and Ca transients alternate large-small. Right panels, When an action potential clamp protocol maintains a constant waveform in V, Ca still shows marked alternations. (Reproduced with permission from Chudin et al.8)

Fig. 3

Fig. 3

Upper panels, 3 slightly different curves modeling Ca release from the SR as a function of SR Ca content. The slope of the rightmost segment of the curve increases from left to right. Lower panels, The change in release curves gives rise to a qualitative change in behavior. Shown are Ca releases as a function of the pacing interval T. Note that, in the relation on the left, shorter pacing intervals do not give rise to alternans, only to increases in the release level, but for the 2 curves on the right, a bifurcation to alternans occurs with increasing slope of the SR release curve. (Right-hand panel data reproduced with permission from Diaz et al.9)

Fig. 4

Fig. 4

Positive vs negative V-Ca coupling (left) gives rise to V-Ca oscillations that are electromechanically in phase or out of phase.

Fig. 5

Fig. 5

Concordant and discordant alternans in a Langendorff guinea pig heart. Left, Paced at 220 milliseconds, the ECG (tracing) shows TWA, with the T wave alternately upright and inverted. The maps at bottom show that repolarization takes longer on beat 1 than on beat 2 (note more light shades and less black in beat 2, indicating faster repolarization). Thus, there is global APD alternans. Right, However, when the heart is paced at 180 milliseconds, very light and very dark areas are found in the same beat, with the areas alternating out of phase from beat to beat. This is discordant alternans, and it manifests on ECG as alternation in the QRS complex as well as the T wave (upper right tracing; reproduced with permission from Pastore et al2).

Fig. 6

Fig. 6

To model the observations of Laurita et al, a gradient of APD was created across the tissue by slowly changing the K current as a function of space. Upper maps, V is shown in gray scale. Middle, When an S2 stimulus is delivered 110 milliseconds after beat 15, it blocks, creating wave break and reentry (next panel), which finally break up into fibrillation (last panel). Lower maps, Here, APD is shown in gray scale for beats 14 and 15. Note that the wave break in the upper panels occurs precisely at the spatial boundary between the positive and negative APD changes, that is, the nodal line (see text that follows; reproduced with permission from Qu et al16).

Fig. 7

Fig. 7

Anterior view of the lower (apical) half of a rabbit heart Langendorff preparation, with wave fronts imaged by V-sensitive dyes. The pacing site is at the rectangular pulse in the upper center. At a pacing interval of 140 milliseconds, 5 consecutive nodal lines all lie together near the apex (dark lines). However, at the faster interval of 130 milliseconds, 5 consecutive nodal lines all lie closer to the pacing site and still perpendicular to the direction of conduction. (Reproduced with permission from Hayashi et al.24)

References

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