Biomedical Frontiers: Fall 1996, Vol.4, No.1
Studying Heart "Memory"

Like nerve cells in the brain that store patterns of events to form memories, cells in the heart can form memories of rhythm patterns. At CPMC, Dr. Michael R. Rosen, Gustavus A. Pfeiffer Professor of Pharmacology and professor of pediatrics, and his associates have studied heart memory for the past five years. Their work--and that of their collaborators at the State University of New York at Stony Brook--indicates that the turnover of proteins in a cardiac myocyte enables the cell to continually adapt to its environment and, as a result, "remember" abnormal rhythm patterns.

"With every heartbeat, the cell is stimulated; then it repolarizes and returns to a resting state," says Dr. Rosen. "The memory process relates to the T wave and repolarization." As the cell repolarizes during periods of abnormal beating, the abnormal pattern of repolarization will be "remembered" by the cell for a period of time. "The more frequently the abnormal beat occurs, the more the altered repolarization pattern is remembered," says Dr. Rosen.

The changes in repolarization can modify the interaction of the heart and antiarrhythmic drugs.

These changes in heart memory may be the result of changes in protein synthesis and signaling pathways, a possibility that Dr. Rosen and his associates are now investigating. Furthermore, heart memory also has significance for the treatment of abnormal rhythms: The changes in repolarization can modify the interaction of the heart and antiarrhythmic drugs, enhancing the action of the drugs in some cases and diminishing it in others. Application of this knowledge should aid in the design of new drugs and devices to modify heart rhythms.

Two abstracts related to this work have been accepted for presentation at the 1996 meeting of the American Heart Association. The abstracts deal with the processes governing the development of long-term memory as well as the role of the renin-angiotensin II system in the genesis of short-term memory. Dr. Rosen also has spoken on the topic of memory at the plenary session of the European Society of Cardiology, and memory will be the topic at a podium session of the AHA.

Proposed schema for the occurrence and effects of cardiac memory. Altered sites of impulse initiation in the heart (such as occur in the setting of cardiac arrhythmias) alter the stress/strain relationships of the ventricular muscle, activating the endogenous cardiac renin-angiotensin system. Angiotensin II, via protein kinase C, induces channel phosphorylation, and the resultant altered ion channel function changes transmyocardial voltage gradients in the heart, inducing memory that persists for relatively short periods. This pathway is also modulated by the sympathetic nervous system, via activation of beta-adrenergic receptors, induction of cyclic AMP synthesis, and protein kinase A. Long-term memory also may be activated via the angiotensin II pathway, but via new protein synthesis. Both types of memory alter the cardiac effective refractory period and thereby modulate the occurrence of arrhythmias in the heart and influence the effects of antiarrhythmic drugs.