Elsevier

Heart Rhythm

Volume 6, Issue 4, April 2009, Pages 564-570
Heart Rhythm

Cell to bedside
Cardiac memory: A work in progress

https://doi.org/10.1016/j.hrthm.2009.01.008Get rights and content

Cardiac memory is a form of electrophysiological remodeling generally considered benign, although it shares transduction pathways with factors that may be pathological, such as angiotensin II and reactive oxygen species. When induced by electrical pacing, memory provides a window into the mechanisms engaged during cardiac device therapy. Emphasis is placed on the complexity of signaling processes occurring downstream to the simple intervention of cardiac pacing and the relationship of resultant ion channel changes to their expression in action potentials and body surface recordings.

Introduction

Nearly 30 years have passed since the late Mauricio Rosenbaum and colleagues1 provided a name for a T-wave change that was neither primary (i.e., activation-dependent and following the vector of the QRS complex that preceded it) nor secondary (i.e., completely independent of the QRS complex and intrinsic to repolarization alone). It had previously been reported in association with intermittent left bundle branch block, ventricular extrasystoles, right ventricular pacing, posttachycardia syndrome, and ventricular preexcitation.2 Common to all interventions were abnormal ventricular activation resulting in a T wave during subsequent sinus rhythm that maintained the vector determined by the earlier, abnormal QRS complex. This characteristic was used to define the phenomenon. Rosenbaum et al1 said the T wave “remembered” the abnormal QRS vector; hence the name cardiac memory. Rosenbaum et al1 opined that altered electrotonus might underlie memory, an idea supported by the experiments of Costard-Jackle et al3 using monophasic electrode recordings in Langendorff-perfused rabbit hearts. The matter of mechanism then rested until the late 1980s, when one of us (M.R.R.) was prevailed upon by Mauricio to dig a little further into the causality of memory before he began losing his own. Work in our and other laboratories3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 has since provided a diversity of information: the simple T-wave change persisting after abnormal activation has multiple causes, all of which seem convergent on altered myocardial stretch. Downstream linkage is via several signal transduction systems and ion channels (including the gap junctional channels responsible for cell–cell coupling and electrotonus). The transduction systems and channels involved share roles in some instances of cardiomyopathy, myocardial ischemia, and congestive failure, but the mechanisms in memory are engaged by a simple experimental intervention: pacing from a ventricular point source to alter activation (see Figure 1 for template). To summarize, although there are multiple forms of cardiac remodeling, cardiac memory can be thought of as a tightly defined (electrocardiographically) form of remodeling with a causality that has some factors in common and others distinct from other forms of remodeling.1, 2, 8, 11, 14

Section snippets

Looking for memory, the long and the short of it

Rosenbaum et al1 showed that as the duration of pacing is prolonged, so is the duration of memory (although the latter persists longer than the inciting event). Based on this information and preliminary experiments, we arbitrarily designated pacing periods of 15 minutes to 2 hours as resulting in short-term memory (lasting minutes to hours), and pacing periods of 2 to 3 weeks as resulting in long-term memory (persisting weeks to months).8, 11, 14 Subsequent experiments have shown these

Pacing, activation, stretch, and memory

Prinzen et al4, 5 used magnetic resonance imaging to show that ventricular pacing alters the pattern of contraction and relaxation throughout the canine left ventricular (LV) wall. This research led us and others to ask whether altered activation or resultant altered stress–strain relationships are requisite for inducing cardiac memory. Jeyaraj et al6 studied wedge preparations from hearts of dogs that had undergone 4 weeks of LV pacing to induce long-term memory. They described increased

Electrophysiology

Janse et al20 studied the T-wave changes in cardiac memory in situ. Under control conditions during atrial pacing, they reported a LV apicobasal gradient with the shortest repolarization times anterobasally and the longest repolarization times posteroapically. They found no significant transmural repolarization gradient in control subjects or after 2 hours of ventricular pacing. Both repolarization time and monophasic APDs shortened during induction of short-term memory, leading them to suggest

Electrophysiology

Rosenbaum et al1 commented on the accumulation of cardiac memory: with continued pacing, the magnitude of the T-wave change increases (Figure 3A) and persists for longer intervals. Shvilkin et al14 studied initiation of long-term memory using tissue slabs isolated from the hearts of dogs LV-paced for 3 weeks. They reported that long-term memory is associated with increased APD in LV epicardium (Figure 3B) and endocardium, but not midmyocardium. This suggested an altered transmyocardial

Conclusion

So what is cardiac memory? It is not identical to memory in other systems. Memory in neurons represents a gain in function, as synaptic protein expression is strengthened.15 In contrast, cardiac memory returns the heart in many ways to an approximation of its neonatal status.12 This is not accompanied by any addition of protein or of any strengthening of cell–cell communication. Rather there is loss: after initiation by altered activation and stretch and with this, local cardiac angiotensin II

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