Control of electrical alternans in canine cardiac purkinje fibers

Abstract

Alternation in the duration of consecutive cardiac action potentials (electrical alternans) may precipitate conduction block and the onset of arrhythmias. Consequently, suppression of alternans using properly timed premature stimuli may be antiarrhythmic. To determine the extent to which alternans control can be achieved in cardiac tissue, isolated canine Purkinje fibers were paced from one end using a feedback control method. Spatially uniform control of alternans was possible when alternans amplitude was small. However, control became attenuated spatially as alternans amplitude increased. The amplitude variation along the cable was well described by a theoretically expected standing wave profile that corresponds to the first quantized mode of the one-dimensional Helmholtz equation. These results confirm the wavelike nature of alternans and may have important implications for their control using electrical stimuli.

FIG. 1

(color). Data from two consecutive action potentials recorded from 6 microelectrodes spaced along the length of a Purkinje fiber (Lead 1 is proximal; Lead 6 is distal) in one representative control experiment. Stimulation was applied to the proximal end of the fiber near microelectrode 1 (x = 0 cm). For each of the three rows [(a), (b), and (c)]: (1) T_* is shown on the left, (2) membrane potential vs time for microelectrodes 1 through 6 (which correspond to x = 0 and 2 cm, respectively) are shown in the left column (before control) and middle column (during control), and (3) the right column shows APD values computed from the six microelectrodes for the same alternate beats before (top panels) and during (bottom panels) control. During control, stimulation was adapted according to Eq. (1). In the middle column, action potentials for which control failed to eliminate alternans are shown in red and blue, while those in which alternans was suppressed are shown in black.

FIG. 2

Alternans magnitude, as recorded by microelectrodes 1 (Lead 1, left panel) and 6 (Lead 6, right panel) from Fig. 1, before control (‘‘Off’’) and during control (‘‘On’’). Periodic pacing and control were applied to the proximal end of the fiber (near microelectrode 1).

FIG. 3

A quantitative comparison of a(x) corresponding to Eq. (3) (solid curve) and five control trials (symbols). For the control-trial data, the APD values for consecutive beats were subtracted and divided by two for each of the six spatial electrodes.