Cell to bedsideCardiac memory: A work in progress
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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Worth Remembering: Cardiac Memory Presenting as Deep Anterior T-Wave Inversions Explained by Intermittent Left Bundle Branch Block
2020, American Journal of CardiologyCardiac memory: The slippery slope twixt normalcy and pathology
2015, Trends in Cardiovascular MedicineCitation Excerpt :short-term, resulting from abnormal ventricular activation. This is initiated and expressed in minutes to hours and appears to be determined by signaling pathways that alter ion channel trafficking [1,15]; long-term, resulting from abnormal activation.
No author has a conflict of interest.