Electrical Restitution Hysteresis

Abstract

T he action potential duration (APD) of ventricular myocytes depends on the length of the preceding diastolic interval (DI) in a relationship termed "electrical restitution." The APD shortens with decreasing cycle length and thus with decreasing DI. 1 The teleological advantage of this phenomenon is that it provides increased time for excitation-contraction coupling at long cycle lengths while preserving diastolic time for coronary perfusion and ventricular filling at short cycle lengths.Restitution of the APD may also lead to rich behavior in beat-to-beat APD fluctuations. At a fixed cycle length, a perturbation in action potential that shortens the APD results in concomitant lengthening of the next DI, given that CLϭAPDϩDI. The restitution relationship dictates that a prolonged DI will lead to lengthening of the next APD. Thus, the initial perturbation results in alternation in APD between values that are shorter or longer than the steady-state APD. Whether the APD oscillations grow or decay depends on whether the slope of the restitution curve in the region near the steady state is greater than or less than unity. 2 In the case of growing APD alternans, regions of myocardium may develop sufficiently long APD on some beats as to be rendered refractory to activation on the subsequent beat. This results in wavebreak and the substrate for reentry and fibrillation. [3][4][5] But there is further complexity in electrical restitution in that the shape and duration of the action potential depend on more than just the DI of the preceding beat. 6 -9 The APD observed at any given DI is not unique and depends on the history of activation sequence leading up to that beat. In this issue of Circulation Research, Wu and Patwardhan 10 report on APD restitution in canine isolated ventricular tissue preparations using oscillatory sequences of DI. These investigators made use of a system they previously developed 11 to provide explicit control over DI by starting a timer when the action potential achieved 90% repolarization and stimulating the tissue when the elapsed time reached the prescribed DI for that beat. They utilized sequences in which DI varied linearly, sinusoidally, and randomly.Wu and Patwardhan 10 found that the relationship between APD and preceding DI followed a hysteresis loop rather than a fixed unimodal curve when DI varied sinusoidally. For a given DI, APD was consistently lower when DI was on the rising limb than when DI was falling. When DI varied randomly, the plot of APD versus preceding DI consisted of points that largely filled the interior of a hysteresis loop. When DI varied linearly (following a triangular wave), the APD-versus-DI curve followed a hysteresis loop similar to that observed during sinusoidally varying DI, although with a somewhat shallower set of slopes. These findings are consistent with those of Elharrar and Surawicz, 6 who showed two decades ago that the restitution curve is shifted higher for sequences with long cycle lengths than that found for sequences with shorter cycle lengths...

Short-term action potential memory and electrical restitution: A cellular computational study on the stability of cardiac repolarization under dynamic pacing

“…Measurement of the electrical restitution of cardiac ventricular AP has been used previously to study memory and stability of repolarization, which have also been related to hysteresis in APD vs DI that develop in dynamic conditions [ 25 , 29 , 43 ]. By means of simulations carried out on a human ventricular AP model [ 34 ], we show that hysteresis affects both APD vs DI and APD vs CL representations of dER, and that the latter is a better marker of memory and stability.…”

“…A link has been found between memory and stability, since an increase in the former frequently increases the latter [ 25 – 28 ]. Part of the linking mechanism has been associated with the hysteresis behavior assumed by dER during periodically varying fast pacing stimulations [ 15 , 25 , 29 ], where the magnitude of APD at a given DI differs depending on whether the magnitude of DI is increasing or decreasing at that time. One key observation has been made by Wu and Patwardan [ 25 ] who showed the effect of hysteresis in dER DI on the evolution of a sudden pacing perturbation, demonstrating that hysteresis tends to buffer activation instability, whereas absence of hysteresis favors APD alternans after the same perturbation.…”

“…All previous studies have been done by looking at dER DI [ 15 , 29 – 31 ], as opposed to dER CL , mainly because of the predictive value attributed to its slope. Hysteresis in dER CL has been shown previously, but with reference to steady-state changes in the type of rhythm (Hopf bifurcations between 1:1, 2:1, 2:2 beating modes) [ 32 , 33 ], or in the amount and sign of APD response for sudden changes in constant CL values [ 2 , 5 ].…”

Microtopographical effects of natural scaffolding on cardiomyocyte function and arrhythmogenesis

“…It is especially critical for an implantable cardiac patch to be resistant to arrhythmia generation [24–27]. Wu and Patwardhan [21] demonstrated that the presence of hysteresis in the relationship action potential duration (APD) vs DI might reduce electrical instabilities (alternans) and thus help prevent malignant arrhythmias such as ventricular fibrillation [22]. Hysteresis is short-term cardiac memory or dependence of the current electrical pulse from previous beats, and was chosen as an indirect measure of electrical stability.…”

“…This is achieved by comparing restitution properties (CTD vs diastolic interval (DI)) [20] upon acceleration of pacing rate (up) and upon deceleration of rate (down). A difference between the two curves is indicative of the presence of hysteresis, and may also be used to predict resistance to arrhythmias [21,22]. …”