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.Electrical alternans is a phenomenon characterized by a beat-to-beat alternation in the duration of the cardiac action potential (APD) [1]. Because heart cells are refractory to further stimulation during an action potential, alternans of APD results in an alternans of refractoriness, the magnitude of which may vary across different regions of the heart. Several studies have shown that the resulting spatial dispersion of refractoriness facilitates the development of local conduction block [2][3][4][5], which may in turn cause the normally planar wave of electrical excitation in cardiac tissue to break and form spiral waves [6]. If the spiral waves also encounter regions of disparate refractoriness, they may disintegrate into multiple wavelets, which may account for the onset of the lethal heart rhythm disorder ventricular fibrillation [7][8][9].Given that APD alternans may be mechanistically linked to the onset of reentrant arrhythmias, its elimination might be an effective antiarrhythmic strategy. Initial work in that direction showed that closed-loop feedback methods could be used to suppress a type of alternans (known as atrioventricular-nodal conduction alternans) with period-doubling dynamics that are related to those of APD alternans [10][11][12][13]. More recently, it was shown that a related control method could terminate APD alternans in isolated frog hearts [14,15]. The latter studies showed clearly that perturbations to the electrical stimulus interval could be used to eliminate APD alternans in a system that does not have spatiotemporally varying repolarization and wavepropagation dynamics (the frog sections were small enough that there were no apparent spatial variations in dynamics). NIH Public Access

Control of electrical alternans in simulations of paced myocardium using extended time-delay autosynchronization

“…For this reason, we refer to R as the history parameter for the ETDAS method. We remark that variants of the special case of ETDAS in which R = 0 (i.e., A n+1 is directly influenced only by the most recent APD value, A n ) have been used for experimental control of alternans both in vivo [14] and in vitro [7,17,28].…”

“…Such findings are supported by theoretical investigations [5,6] that demonstrate that large-amplitude alternans can serve as a mechanism for the breakup of spiral waves of electrical activity, leading to turbulent wave behavior reminiscent of fibrillatory patterns. It is believed that this sequence of events may be preventable by controlling alternans locally [7][8][9].…”

“…As an example of the latter, consider an in vivo experiment in which an animal's intact SA node sets the BCL. Typically, in order to take over the heart's rhythm, the controller must preempt the stimuli from the SA node, meaning that the BCL can only be shortened [7,14].…”

“…As a step towards achieving this ultimate goal, several research groups have attempted to suppress alternans [7,17] or more complex behaviors [18] in vitro with preparations that have limited spatial extent. In these experiments, BCL is often determined from externally supplied electrical stimuli, and small adjustments to BCL are used to maintain a 1:1 rhythm.…”

“…Notably, by writing the ADIC scheme in an apparently different but equivalent way, one finds that the ADIC scheme is actually a special case of ETDAS and the important advantages of ADIC are shared by all ETDAS schemes. ETDAS has several noteworthy features, such as: (i) the control domain (i.e., the set of all possible parameter choices for which control successfully suppresses alternans) is large; (ii) various special cases of ETDAS have been used to control AV-nodal conduction time alternans in humans in vivo [14] as well as APD alternans in canines [7], frogs [17] and rabbits [28] in vitro; (iii) ETDAS is amenable to experimental setup and has already been used for chaos control in physical systems [24,29]; (iv) it is possible to restrict the ETDAS parameters to achieve control while allowing only shortening of BCL; (v) the additional freedom gained by using ETDAS as opposed to restrictive cases such as ADIC allows the experimenter to choose parameters in such a way that sensitivity to background noise is reduced; and (vi) because ETDAS has been studied for over a decade, one may exploit prior mathematical analysis [23,24] as a guide for choosing system parameters that lead to successful control of alternans.…”