Cardiac Memory Evolves With Age in Association With Development of the Transient Outward Current

Background— Calcium-insensitive transient outward current (Ito) is important to the development of cardiac memory (CM), which itself reflects the capacity of the heart to remodel electrophysiologically. We used cardiac pacing to test the hypothesis that CM evolution can be explained by developmental maturation of Ito. Methods and Results— Acutely anesthetized dogs from 1 day old to adult were paced from the left ventricle (VP, n=29) or left atrial appendage (AP, n=12) to induce CM. T-wave vector displacement (TVD) obtained during VP was greater than with AP (adults, 0.39±0.06 mV; neonates, 0.04±0.01 mV; P<0.05). TVD began to increase at ≈40 days of age, reaching adult levels by ≈200 days. Microelectrode studies performed in 18 dogs (ages 3 to 94 days) after completing the CM protocol and 20 additional dogs (1 day old to adult) revealed that the epicardial action potential notch was absent in neonates, became apparent in the young, and was deepest in adults. The relationship between TVD and epicardial notc...